{ "generatedAt": "2026-11-05T07:19:26.995Z", "emaTimestamp": "2026-11-05T05:49:30Z", "products": { "abemaciclib__verzenios": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/verzenios-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/verzenios-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000365494","type":"N","opinion":"2026-08-25","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet to correct the drug interaction mechanism wording in section ‘2. What you need to know before you take Verzenios’ under ‘Other medicines and Verzenios’ to align with the information provided in the SmPC. Additionally, the MAH took the opportunity to introduce minor corrections to the BG and ES package leaflet to align with the approved EN text."}, {"id":"EMA/VR/0000315519","type":"IAIN","opinion":"2026-01-27","decision":"2026-03-12","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"EMA/VR/0000307389","type":"II","opinion":"2026-01-29","decision":"2026-03-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final OS data from study monarchE (I3Y-MC-JPCF) listed as a PAES in the Annex II; this is a randomized, open-label, phase 3 study of abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone in patients with high risk, node positive, early stage, hormone receptor positive, human epidermal receptor 2 negative, breast cancer. The Annex II and Package Leaflet are updated accordingly. The RMP version 2.1 has also been submitted."}, {"id":"EMA/VR/0000282650","type":"II","opinion":"2025-09-18","decision":"2026-03-12","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the final results from study J1S-MC-JP04, a PIP study and submitted in accordance with Article 46 of Regulation (EC) No 1901/2006; study J1S-MC-JP04is a randomized, open-label, phase 2 study evaluating abemaciclib in combination with irinotecan and temozolomide in participants with relapsed or refractory Ewing’s sarcoma."}, {"id":"EMA/VR/0000248638","type":"IB","opinion":"2025-03-07","decision":"2026-03-12","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update ANNEX IID to amend the due of the monarchE study from June 2025 to June 2026."}, {"id":"II/0033","type":"II","opinion":"2024-07-04","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUSA/00010724/202309","type":"PSUSA","opinion":"2024-04-25","decision":"2024-06-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - abemaciclib PSUSA/10724/202309."}, {"id":"II/0028","type":"II","opinion":"2023-11-09","decision":"2024-06-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on “arterial thromboembolic events“, based on a safety review. The Package Leaflet is updated accordingly. In addition the MAH took the opportunity to update section 9 of the SmPC."}, {"id":"IAIN/0035","type":"IAIN","opinion":"2024-06-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0025","type":"R","opinion":"2023-04-26","decision":"2023-06-23","affects":["SmPC","Annex II","Labelling"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0024","type":"II","opinion":"2023-01-26","decision":"2023-06-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include overall survival data based on final results from study MONARCH 2; this is a randomized, double-blind, placebo-controlled, phase 3 study of fulvestrant with or without abemaciclib, a CDK4/6 Inhibitor, for women with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer."}, {"id":"II/0021","type":"II","opinion":"2022-01-27","decision":"2022-04-01","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include second OS interim results from study MONARCH 3; this is a randomised, double blind, placebo-controlled phase 3 study of Nonsteroidal Aromatase Inhibitors (Anastrozole or Letrozole) plus LY2835219, a CDK4/6 Inhibitor, or Placebo in Postmenopausal Women with Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer with No Prior Systemic Therapy in this Disease Setting."}, {"id":"II/0016/G","type":"II","opinion":"2021-05-20","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include OS interim results from MONARCH 3 study, a randomised, double blind, placebo controlled phase 3 study in women with HR positive, HER2 negative locally advanced or metastatic breast cancer who had not received prior systemic therapy in this disease setting. In addition, the MAH is updating the ATC code in the SmPC. The MAH is also taking the opportunity to update the list of local representatives in the Package Leaflet in line with the QRD template 10.2."}, {"id":"II/0013","type":"II","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","5.1","5.3"],"scope":"Extension of indication to include Verzenios in combination with endocrine therapy for adjuvant treatment of patients with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence; as a consequence, section 4.1, 4.2, 4.4, 4.6, 4.8, 5.1 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted."}, {"id":"IAIN/0020","type":"IAIN","opinion":"2021-08-05","decision":"2022-04-01","affects":["SmPC","Labelling"],"codes":["B.II.e.6.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that affects the product information"}, {"id":"II/0008","type":"II","opinion":"2020-01-16","decision":"2020-12-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to include the results of the interim OS analysis from study MONARCH 2, a randomised, double-blind, placebo-controlled, phase 3 study of fulvestrant with or without abemaciclib, for women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer."}, {"id":"IB/0009","type":"IB","opinion":"2019-12-13","decision":"2020-12-17","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0006","type":"II","opinion":"2019-12-12","decision":"2020-01-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add interstitial lung disease (ILD)-like events (including pneumonitis) as new adverse drug reactions together with a related warning and dose adjustments recommendations. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 10.1 and make few corrections to the PL to bring it in line with the SmPC."}, {"id":"II/0003","type":"II","opinion":"2019-09-19","decision":"2019-10-21","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.1"],"scope":"Update of section 4.2 of the SmPC in order to add a criterion for discontinuing abemaciclib in the event of specific hepatic changes based on available safety data. Furthermore, section 4.5 of the SmPC is updated in order to update the information on contraceptive methods. In addition, the Marketing authorisation holder (MAH) took the opportunity to make editorial changes to section 5.1 of the SmPC and to the list of local representatives in the PL."}, {"id":"IAIN/0002/G","type":"IAIN","opinion":"2018-11-26","decision":"2019-10-21","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2018-10-12","decision":"2019-10-21","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"} ] }, "abiraterone__zytiga": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zytiga-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"N/0075","type":"N","opinion":"2024-10-16","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0071/G","type":"IB","opinion":"2022-06-28","decision":"2023-09-15","affects":["SmPC"],"codes":["B.II.f.1.b.1","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update section 2 of the SmPC to add an equivalency statement between abiraterone and abiraterone acetate."}, {"id":"II/0061","type":"II","opinion":"2020-06-11","decision":"2022-01-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"To update the Summary of Product Characteristics section 4.4 and 4.5 and package leaflet as per the PRAC recommendations published on 10th Feb 2020 to add a new warning on Hypoglycemia, the Package Leaflet is updated accordingly. In addition, some minor updates have also been made to Annex II of the product information."}, {"id":"IB/0067/G","type":"IB","opinion":"2021-07-19","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0064","type":"IAIN","opinion":"2020-12-03","decision":"2022-01-06","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0058","type":"II","opinion":"2019-12-12","decision":"2020-04-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To update section 5.1 of the SmPC based on final results from study PCR3011 (Lattitude); this is a randomised, double-blind, placebo-controlled study designed to determine the efficacy of abiraterone acetate and low-dose prednisone in men with metastatic hormone-naive prostate cancer. The MAH took the occasion to update the product information as per the latest QRD version and to update local representative for Spain and Hungary in the package leaflet."}, {"id":"IB/0055","type":"IB","opinion":"2019-02-26","decision":"2020-04-23","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00000015/201804","type":"PSUSA","opinion":"2018-12-13","decision":"2019-02-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - abiraterone"}, {"id":"N/0053","type":"N","opinion":"2018-10-12","decision":"2019-02-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0050","type":"N","opinion":"2018-06-12","decision":"2019-02-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0046","type":"N","opinion":"2017-01-06","decision":"2017-11-15","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Annex IIIA to grey shade the text on the blister foil-immediate packaging of the 500 mg film coated tablets, as agreed with QRD. In addition, the MAH took the opportunity to make linguistic amendments in the CS, DE, EL, ES, HU, IT, MT, PT and RO Labelling and DE package leaflet. Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0047","type":"II","opinion":"2017-10-12","decision":"2017-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include treatment of newly diagnosed high risk metastatic hormone sensitive prostate cancer (mHSCP) in adult men in combination with androgen deprivation therapy (ADT) for Zytiga plus prednisone or prednisolone; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. The Risk Management Plan was updated in the light of the data submitted (version 14.2). In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"X/0039","type":"X","opinion":"2016-09-15","decision":"2016-11-09","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to introduce a new pharmaceutical form associated with new strength (500mg film-coated tablets)."}, {"id":"N/0043","type":"N","opinion":"2016-06-10","decision":"2016-11-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of the local representatives for Sweden and Romania. Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"R/0038","type":"R","opinion":"2016-04-01","decision":"2016-05-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0037","type":"II","opinion":"2015-12-10","decision":"2016-05-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8","5.1"],"scope":"Update of section 4.5 of the SmPC to include a statement highlighting the potential interaction between spironolactone and abiraterone and section 5.1 of the SmPC in order to highlight the fact that spironolactone was not allowed to be used in the pivotal studies for ZYTIGA as spironolactone binds to the androgen receptor and may increase PSA levels. In addition, the Marketing authorisation holder (MAH) took the opportunity to a make minor editorial change in section 4.8 of the SmPC."}, {"id":"II/0036/G","type":"II","opinion":"2016-01-28","decision":"2016-05-26","affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"II/0027","type":"II","opinion":"2015-06-25","decision":"2016-05-26","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0025","type":"II","opinion":"2014-11-20","decision":"2015-07-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0022","type":"II","opinion":"2014-07-24","decision":"2015-07-28","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IG/0526/G","type":"IG","opinion":"2015-03-04","decision":"2015-07-28","affects":["Annex II","PL"],"codes":["A.5.a","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Replacement or addition of a manufacturing site for the FP - Secondary packaging site"}, {"id":"PSUV/0019","type":"PSUV","opinion":"2014-05-22","decision":"2014-07-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0018/G","type":"II","opinion":"2014-05-22","decision":"2014-07-18","affects":["SmPC","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC with information regarding OATP1B1 and CYP2C8 inhibition by abiraterone based on the results of the drug-drug interaction studies FK10383 and 212082PCR1011, respectively, included in the RMP. The MAH took the opportunity to update due dates of studies included in the RMP and address minor updates requested in conclusion to the assessment of previous RMP versions. Changes were also made to the PI to bring it in line with the SmPC guideline. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"PSUV/0017","type":"PSUV","opinion":"2013-11-21","decision":"2014-01-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0014/G","type":"II","opinion":"2013-11-21","decision":"2014-01-16","affects":["SmPC","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add allergic alveolitis as a rare Adverse Drug Reaction (ADR) following one relevant case from the post-marketing setting. The Package Leaflet was proposed to be updated accordingly. Submission of the report of a food-interaction study included in the RMP, which did not require changes to the Product Information were proposed in consequence. Update of the list of local representatives in the Package Leaflet."}, {"id":"II/0012","type":"II","opinion":"2013-09-19","decision":"2014-01-16","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC based on the results of a 6-month mouse and a 2-year rat carcinogenicity study requested by the CHMP (MEA 011)."}, {"id":"II/0010","type":"II","opinion":"2013-07-25","decision":"2014-01-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.9"],"scope":"Update of sections 4.4 and 4.5 of the SmPC in order to include a warning against use of strong CYP3A4 inducers during treatment with abiraterone and to amend the information on interactions of abiraterone with inducers and inhibitors of CYP3A4, based on the results of two relevant studies (PCR 1002 and PCR 1003). The MAH also took the opportunity to make a minor amendment of information related to overdose in section 4.9 of the SmPC and to update the list of local representatives in the Package Leaflet. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"II/0004/G","type":"II","opinion":"2012-11-15","decision":"2012-12-18","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a","C.I.4"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.6","4.8","5.1","5.2","5.3"],"scope":"Extension of Indication to include new population for Zytiga in combination with prednisone or prednisolone for the treatment of metastatic castration resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated."}, {"id":"II/0003","type":"II","opinion":"2012-07-19","decision":"2012-08-30","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to introduce a warning on CYP2C8 inhibition by abiraterone. In addition, the MAH took the opportunity to introduce changes to the PL requested in conclusion to the assessment of FUM 010 and consequential changes to the Labelling. Furthermore, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0002","type":"II","opinion":"2012-04-19","decision":"2012-05-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","6.5"],"scope":"Update of section 4.8 of the SmPC in order to include bone fractures as an adverse drug reaction of Zytiga. The Package Leaflet is updated in accordance. The PL is amended in order to reflect existing warnings in the SmPC and minor changes are made to sections 4.4, 4.8 and 6.5 of the SmPC and to the PL. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI is being brought in line with the latest QRD template version 8.1 and minor editorial changes are made to it."} ] }, "abiraterone-acetate__abiraterone-krka": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/abiraterone-krka-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"N/0007","type":"N","opinion":"2025-01-28","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0003","type":"IB","opinion":"2022-11-23","decision":"2022-12-16","affects":["SmPC","Labelling","PL"],"codes":["C.I.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the SPC, Labelling or PL of a generic/hybrid/biosimilar products following assessment of the same change for the reference product - Implementation of change(s) for which NO new additional data is required to be submitted by the MAH"}, {"id":"IB/0002","type":"IB","opinion":"2022-07-05","decision":"2022-12-16","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"} ] }, "acalabrutinib__calquence": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/calquence-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/calquence-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf-0","https://www.ema.europa.eu/en/documents/procedural-steps-after/calquence-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00010887/202510","type":"PSUSA","opinion":"2026-06-25","decision":"2026-08-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - acalabrutinib"}, {"id":"EMA/VR/0000332092","type":"IB","opinion":"2026-03-12","decision":"2026-05-26","affects":["SmPC"],"codes":["C.1.z","C.z"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"To update section 4.2 of the Calquence SmPC is in response to a request from EMA to provide guidance on dose reductions for acalabrutinib when used in combination with venetoclax (with or without obinutuzumab) for the treatment of adult patients with previously untreated CLL."}, {"id":"EMA/R/0000247050","type":"R","opinion":"2025-05-22","decision":"2025-07-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation."}, {"id":"II/0028","type":"II","opinion":"2025-04-25","decision":"2025-06-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include CALQUENCE in combination with venetoclax with or without obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), based on interim results from study AMPLIFY (D8221C00001); this is a randomised, multicentre, open-label, phase 3 study of acalabrutinib in combination with venetoclax with and without obinutuzumab compared to investigator’s choice of chemoimmunotherapy in subjects with previously untreated CLL without del(17p) or TP53 Mutation. As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"N/0022","type":"N","opinion":"2024-02-16","decision":"2025-05-02","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0026","type":"II","opinion":"2025-02-27","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","5.1"],"scope":"Extension of indication to include CALQUENCE as monotherapy for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy based on final results from study ACE-LY-004 (D8225C00002); this is an open-label, phase 2 study of ACP-196 in subjects with Mantle Cell Lymphoma. As a consequence, sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 7.2 of the RMP has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI."}, {"id":"II/0025","type":"II","opinion":"2025-03-27","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include Calquence in combination with bendamustine and rituximab (BR) as treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous stem cell transplant (ASCT) based on interim results from study ACE-LY-308 (ECHO, D8220C00004); this is a Phase III, randomized, double-blind, placebo-controlled, multicenter study of BR alone versus in combination with acalabrutinib (ACP-196) in subjects with previously untreated MCL. As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 6, succession 2 of the RMP has also been submitted."}, {"id":"II/0015","type":"II","opinion":"2023-05-12","decision":"2023-08-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the interim report of study ACE-CL-007; a randomized, multicenter, open-Label, 3-arm phase 3 study of obinutuzumab in combination with chlorambucil, ACP-196 in combination with obinutuzumab, and ACP-196 monotherapy in subjects with previously untreated chronic lymphocytic leukemia."}, {"id":"II/0013","type":"II","opinion":"2023-01-12","decision":"2023-08-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy and safety information based on final results from study ACE-CL-309 (A Phase 3 randomized open-label active-control study investigating Calquence for the Treatment of Subjects With Relapsed or Refractory Chronic Lymphocytic Leukaemia) listed as a category 3 study in the RMP."}, {"id":"IB/0020","type":"IB","opinion":"2023-06-14","decision":"2023-08-16","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0017","type":"IAIN","opinion":"2023-05-03","decision":"2023-08-16","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"X/0009/G","type":"X","opinion":"2022-12-15","decision":"2023-02-20","affects":["SmPC","Labelling","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0007","type":"II","opinion":"2021-09-30","decision":"2022-07-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC following submission of the final report from ACE-HV-114, an open-label, fixed sequence study in healthy subjects to assess the pharmacokinetics of acalabrutinib and its active metabolite, ACP-5862, when administered alone and in combination with moderate CYP3A4 inhibitors fluconazole or isavuconazole. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.2."}, {"id":"II/0005","type":"II","opinion":"2021-06-24","decision":"2022-07-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Submission of the final report from study XS-1468 to further characterise the plasma protein binding of acalabrutinib and its metabolite ACP-5862 in different species. Section 5.2 of the SmPC is updated accordingly to reflect the new plasma protein binding data."}, {"id":"II/0004","type":"II","opinion":"2021-11-11","decision":"2022-07-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4","5.3"],"scope":"Submission of the final report of the nonclinical Study 20266648 (5336BV) (Acalabrutinib: Neutral Red Uptake Phototoxicity Assay in BALB/c 3T3 Mouse Fibroblasts), in response to the CHMP recommendation to submit results from a modified 3T3 NRU phototoxicity study with adjusted wavelengths. SmPC sections 4.4 and 5.3 were updated accordingly."} ] }, "adagrasib__krazati": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/krazati-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/krazati-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000363088","type":"IB","opinion":"2026-08-20","decision":null,"affects":["SmPC","Annex II"],"codes":["C.9.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To revise the due date for the submission of the final clinical study report for study 849-012 (KRYSTAL 12), listed as PAES in Annex IIE and in the RMP from Q3 2026 to Q2 2027. In addition, the MAH took the opportunity to update the date of renewal in section 9 of the SmPC."}, {"id":"II/0010/G","type":"II","opinion":"2025-03-27","decision":"2025-11-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"A grouped application consisting of: C.I.4: Submission of results from study 849-012 (KRYSTAL-12) listed as a specific obligation in the Annex II. This is a Randomized Phase 3 Study of MRTX849 versus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer with KRAS G12C Mutation. Annex IIE has been updated accordingly. The RMP version 2.1 is agreed. The MAH took the opportunity to make editorial changes to the SmPC and package leaflet. C.I.4: Update of section 4.8 of the SmPC in order to update safety information based on an integrated analysis of data from interventional studies 849-012 (KRYSTAL-12), 849-007 (KRYSTAL-7) and 849-001 (KRYSTAL-1)."}, {"id":"IAIN/0009","type":"IAIN","opinion":"2024-08-30","decision":"2024-11-18","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0003","type":"IAIN","opinion":"2024-05-21","decision":"2024-11-18","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"T/0002","type":"T","opinion":"2024-04-04","decision":"2024-04-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "afatinib__giotrif": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/giotrif-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/giotrif-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000326537","type":"IB","opinion":"2026-05-08","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["Q.II.e.6.a.2","Q.II.e.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of a new pack size or change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes; Change in type of container or addition of a new container - Solid, semi-solid and non-sterile liquid pharmaceutical forms"}, {"id":"EMA/VR/0000261894","type":"IAIN","opinion":"2025-03-31","decision":"2026-03-03","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH"}, {"id":"IB/0046","type":"IB","opinion":"2025-02-10","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To bring the annexes in line with the current QRD template and in addition to introduce several minor editorial changes in the different EU languages. The MAH has also taken the opportunity to update the information on the local representative in Norway and to remove the local representative for UK(NI)."}, {"id":"IB/0041","type":"IB","opinion":"2023-06-19","decision":"2024-06-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0037","type":"N","opinion":"2021-04-06","decision":"2021-12-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0034/G","type":"IAIN","opinion":"2020-10-08","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0031","type":"II","opinion":"2019-11-28","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to introduce a warning and to add gastrointestinal (GI) perforation as an additional adverse drug reaction based on summaries of clinical trial and post-marketing safety data, respectively. The Package Leaflet and the RMP (finally agreed version 8.1) are updated accordingly. The RMP also includes the update of the RMP due to the GVP revision 2 template. In addition, the MAH took the opportunity to update the list of the local representatives in the package leaflet."}, {"id":"II/0028","type":"II","opinion":"2018-06-28","decision":"2019-06-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the efficacy section with data in EGFR TKI-naïve NSCLC patients whose tumours harbour uncommon EGFR mutations based on a meta-analysis across three trials (1200.22, 1200.32 and 1200.34). In addition, the Marketing authorisation holder (MAH) took the opportunity to implement minor linguistic amendments to the translations of the product information annexes: BG, CS, DE, DK, FI, IS, IT, NO, PT, SE and SK."}, {"id":"R/0026","type":"R","opinion":"2018-03-22","decision":"2018-05-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0023","type":"II","opinion":"2017-07-13","decision":"2017-10-23","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add the adverse reaction nail disorders with a frequency common based on the results of study 1200.131 and supportive evidence from EGFR TKJ comparator studies. The package leaflet is updated accordingly. In addition, the MAH took the opportunity to make some editorial changes to the polish product information."}, {"id":"II/0022","type":"II","opinion":"2017-02-23","decision":"2017-10-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the information about the major mechanism of acquired resistance to afatinib. In addition, the Marketing authorisation holder (MAH) took the opportunity to add the side effects ‘itching’ and ‘dry skin’ with frequency very common to the package leaflet to bring it in line with the SmPC."}, {"id":"II/0020","type":"II","opinion":"2016-11-10","decision":"2017-10-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC in order to include a table comparing adverse drug reactions (with frequency very common) observed in the global, randomised, open-label, Phase IIb trial (LUX-Lung 7) with afatinib and gefitinib and update of section 5.1 of the SmPC in order to add the results of the primary analysis of this study."}, {"id":"II/0019","type":"II","opinion":"2016-09-15","decision":"2016-11-14","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC in order to add toxic epidermal necrolysis to the existing warning on skin related adverse events and update of section 4.8 of the SmPC to add toxic epidermal necrolysis/Stevens Johnson syndrome as a frequency rare, based on post-marketing experience. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to place the required safety features on the packaging (i.e. Unique Identifier – 2D Barcode and Human Readable Data) in line with the latest QRD template version 10. The requested variation proposed amendments to the Summary of Product Characteristics, Labelling and Package Leaflet."}, {"id":"II/0017","type":"II","opinion":"2016-10-13","decision":"2016-11-14","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update the information regarding renal impairment, which has been introduced following completing of the Phase I study 1200.2016. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to implement editorial changes in the SmPC and to update the labelling (Annex IIIA) in line with QRD template, version 9.1."}, {"id":"N/0006","type":"N","opinion":"2014-10-17","decision":"2016-03-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0015","type":"II","opinion":"2015-11-19","decision":"2016-03-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add the new adverse reaction pancreatitis; the Package Leaflet has been updated accordingly. Furthermore, the MAH has implemented the latest QRD template, version 9.1, by amending the PSUR standard statement in Annex II as well as by introducing a combined SmPC for all four approved product strengths."}, {"id":"II/0014","type":"II","opinion":"2015-09-24","decision":"2016-03-31","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.2"],"scope":"Update of sections 4.6 and 5.2 of the SmPC in order to update the pharmacokinetic information based on results from PK sub-study in patients treated for 6 months or longer. In addition, editorial changes have been proposed in the PI."}, {"id":"II/0013","type":"II","opinion":"2015-09-24","decision":"2016-03-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add nausea and vomiting with the frequency very common based on clinical data from the Phase III trial LUX-Lung 8 (Trial 1200.125). The Package Leaflet is updated accordingly."}, {"id":"II/0012","type":"II","opinion":"2016-02-25","decision":"2016-03-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indications to include patients with locally advanced or metastatic Non-small cell lung cancer (NSCLC) of squamous histology progressing on or after platinum-based chemotherapy."}, {"id":"II/0009","type":"II","opinion":"2015-07-23","decision":"2016-03-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to amend the clinical trial section of the SmPC by updated overall survival (OS) data from the pivotal Phase Ill trial LUX-Lung 3. The MAH made a correction of a typo error in Annex II. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the Spanish and Portuguese local representatives in the Package Leaflet."} ] }, "aflibercept__zaltrap": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zaltrap-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"N/0072","type":"N","opinion":"2024-08-27","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0070","type":"II","opinion":"2023-10-05","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC in order to update information regarding the duration of contraceptive use after cessation of treatment. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0067/G","type":"II","opinion":"2022-12-15","decision":"2024-01-25","affects":["Annex II"],"codes":["B.I.a.1.j","B.I.b.2.d","B.I.a.4.d","B.I.a.1.k","B.I.a.2.a","B.I.b.2.e","B.I.a.1.f","B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Replacement or addition of a site where batch control/testing takes place and any of the test method at the site is a biol/immunol method; Change in test procedure for AS or starting material/reagent/intermediate - Substantial change to or replacement of a biological/immunological/immunochemical test method or a method using a biological reagent for a biological AS; Change to in-process tests or limits applied during the manufacture of the AS - Widening of the approved in-process test limits, which may have a significant effect on the overall quality of the AS."}, {"id":"T/0068","type":"T","opinion":"2022-10-31","decision":"2022-11-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0066","type":"N","opinion":"2022-07-13","decision":"2022-11-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0063","type":"N","opinion":"2021-11-08","decision":"2022-11-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"WS/1829","type":"WS","opinion":"2020-11-12","decision":"2021-12-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0052","type":"IAIN","opinion":"2019-10-30","decision":"2020-10-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0037","type":"R","opinion":"2017-07-20","decision":"2017-09-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0035","type":"II","opinion":"2017-02-23","decision":"2017-09-21","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update the Product Information (SmPC, section 5.1 Pharmacodynamic properties) to reflect the results of the biomarker programme encompassing the EFC10262, EFC10668 and EFC11338 studies in order to fulfil the Annex II condition of Zaltrap, aflibercept 25 mg/ml, Concentrate for solution for infusion (EMEA/H/C/002532)."}, {"id":"II/0026","type":"II","opinion":"2016-09-15","decision":"2016-10-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add the adverse reactions cardiac failure and ejection fraction decreased and to recommend the discontinuation of Zaltrap in case these adverse reactions occur. This update reflects the results of a safety cumulative review. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"PSUSA/00010019/201508","type":"PSUSA","opinion":"2016-02-25","decision":"2016-04-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - aflibercept (oncological indication(s))"}, {"id":"N/0019","type":"N","opinion":"2015-08-06","decision":"2016-04-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUV/0009","type":"PSUV","opinion":"2014-09-25","decision":"2014-11-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"N/0003","type":"N","opinion":"2013-09-25","decision":"2014-06-27","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0007","type":"II","opinion":"2013-12-19","decision":"2014-06-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.4 of the SmPC in order to amend the existing warnings on proteinuria in line with a proposed amendment to the CCDS. Moreover, a minor rewording of the recommendation regarding recurrent hypertension is introduced in section 4.2 of the SmPC and the warning on hypertension in section 4.4 of the SmPC is amended accordingly. In addition, the MAH took the opportunity to update Annex II in line with the QRD template version 9 and to update the details of the local representatives in the Package Leaflet."}, {"id":"IA/0001","type":"IA","opinion":"2013-06-21","decision":"2014-06-27","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "alectinib__alecensa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/alecensa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/alecensa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000313101","type":"II","opinion":"2026-01-29","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update sections 4.8 and 5.1 of the SmPC to update the safety and efficacy information based on final results from study BO28984 (ALEX) listed as a recommendation; this is a Phase 3 interventional randomized, multicenter, open-label study of alectinib versus crizotinib in treatment-naive Anaplastic Lymphoma Kinase (ALK)-positive advanced Non−Small Cell Lung Cancer. The Package Leaflet was updated accordingly. In addition, the MAH took the opportunity to delete the details of local representatives for UK (Northern Ireland), to change the contact number for the NL local representative and to implement formatting edits to the list of local representatives in the Package Leaflet."}, {"id":"II/0048","type":"II","opinion":"2024-10-17","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6"],"scope":"To update sections 4.4 and 4.6 of the SmPC to update the safety information to amend the duration of the period for which female patients of child-bearing potential must use highly effective contraceptive methods following the last dose of Alecensa, and must be informed of potential harm to the fetus in the event of pregnancy, from 3 months to 5 weeks and to also include a new recommendation for males with female partners of childbearing potential to use highly effective contraception during treatment and for at least 3 months after the last dose, based on the latest guidelines on contraception requirements for drugs with aneugenic potential. The Package Leaflet is updated accordingly."}, {"id":"N/0046","type":"N","opinion":"2023-03-15","decision":"2024-06-06","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0047","type":"II","opinion":"2024-04-25","decision":"2024-06-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the use of Alecensa as monotherapy in adult patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) as adjuvant treatment following tumour resection, based on final results from study BO40336 (ALINA), a randomized, active controlled, multicenter, open-label, Phase III study designed to evaluate the efficacy and safety of alectinib compared with platinum-based chemotherapy in the adjuvant setting in patients with completely resected Stage IB (tumours 4 cm) to Stage IIIA ALKpositive NSCLC. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0037/G","type":"II","opinion":"2022-06-23","decision":"2022-08-02","affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add a new warning, dose modification advice and description of the known ADR haemolytic anaemia based on an updated Drug Safety Report; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce editorial updates in the English, Maltese, Romanian, French, Swedish and Italian product information. Moreover, the ATC code for alectinib is being updated from L01XE36 to L01ED03."}, {"id":"IB/0040/G","type":"IB","opinion":"2022-06-15","decision":"2022-08-02","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.I.d.1.a.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data"}, {"id":"R/0039","type":"R","opinion":"2022-05-19","decision":"2022-07-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0034","type":"II","opinion":"2021-09-02","decision":"2022-07-15","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Haemolytic anaemia was added to the list of ADRs in section 4.8 of the SmPC with frequency uncommon."}, {"id":"II/0033","type":"II","opinion":"2021-09-02","decision":"2022-07-15","affects":["SmPC","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Submission of an updated RMP version 3.1 in order to remove the safety concern of missing information - long term safety, based on a report of the cumulative safety data from the pivotal Phase III clinical trial ALEX (BO28984). The MAH has also taken the opportunity to update the RMP to remove study BO40643 from the pharmacovigilance plan, following assessment in procedure EMEA/H/C/004164/II/0030. In addition changes to section 4.8 of the SmPC and section 4 of the leaflet were made in order to update frequency and grades of adverse reactions taking into account the new safety data from ALEX study (BO28984)."}, {"id":"PSUSA/00010581/201907","type":"PSUSA","opinion":"2020-01-30","decision":"2020-04-03","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - alectinib"}, {"id":"N/0017","type":"N","opinion":"2018-08-09","decision":"2020-04-03","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0010","type":"II","opinion":"2018-04-26","decision":"2018-05-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update information on the effect of hepatic impairment on the pharmacokinetics of alectinib based on final results from study NP29783. The Package Leaflet is updated accordingly. The RMP has also been updated to version 3.0. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest EC guidance regarding warning statements on sodium."}, {"id":"T/0013","type":"T","opinion":"2018-02-20","decision":"2018-03-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0001","type":"II","opinion":"2017-10-12","decision":"2017-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of Indication for Alecensa (alectinib) to first line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) including final data report of study BO28984 object of the SOB in the annex II; as a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC and Annex II are updated. The Package Leaflet and the RMP are updated in accordance."}, {"id":"N/0006","type":"N","opinion":"2017-06-27","decision":"2017-12-01","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0003","type":"II","opinion":"2017-06-09","decision":"2017-12-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add \"Increased blood alkaline phosphatase\" as new Adverse Drug Reaction with a common frequency identified during routine signal detection. The package leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce some formatting changes in the Product Information."}, {"id":"IB/0008/G","type":"IB","opinion":"2017-09-25","decision":"2017-12-01","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.1","B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Change in type/addition of a new container - Solid, semi-solid and non-sterile liquid pharmaceutical forms; Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IB/0002","type":"IB","opinion":"2017-04-18","decision":"2017-12-01","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "alpelisib__piqray": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/piqray-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/piqray-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000317159","type":"II","opinion":"2026-07-23","decision":"2026-08-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for PIQRAY in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following an endocrine-based regimen; based on the primary analysis (DCO 15-Oct-2024) from the Phase III Study CBYL719C2303 (C2303, EPIK-B5)."}, {"id":"EMA/VR/0000275207","type":"II","opinion":"2025-10-02","decision":"2026-01-30","affects":["Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"The final report for study CBYL719C2005, listed as a category 3 study in the RMP, was submitted. This is a non-interventional Post-authorisation Safety Study (PASS)/survey that was conducted to assess healthcare professionals’ knowledge on management of hyperglycemia when using alpelisib in selected EU/EEA countries. The Annex II and RMP (version 9.0) have been updated accordingly."}, {"id":"EMA/VR/0000263396","type":"II","opinion":"2025-07-24","decision":"2026-01-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2","5.3"],"scope":"Update of section 5.3 of the SmPC in order to reflect the results of the 2-year carcinogenicity study conducted in rats (study R2070118). In addition, the MAH took the opportunity to correct sections 4.5 and 5.2 of the SmPC with regards to the drug-drug interaction study conducted with the CYP3A4 substrate everolimus."}, {"id":"EMA/VR/0000262559","type":"IB","opinion":"2025-04-28","decision":"2026-01-30","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in the shelf-life or storage conditions of the finished product - Change to an approved stability protocol"}, {"id":"EMA/VR/0000247317","type":"IAIN","opinion":"2025-01-30","decision":"2026-01-30","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0028","type":"R","opinion":"2024-12-12","decision":"2025-02-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0025","type":"II","opinion":"2024-07-11","decision":"2025-02-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to update the frequency of some Adverse Drug Reactions (ADRs) as well as safety information based on the final results from study CBYL719C2301 (SOLAR-1), a randomized, double-blind, placebo-controlled, international, multicenter, Phase III study to determine the efficacy and safety of treatment with alpelisib plus fulvestrant versus placebo plus fulvestrant in men and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer which progressed on or after AI (Aromatase Inhibitor) treatment. The Package Leaflet is updated accordingly."}, {"id":"II/0022/G","type":"II","opinion":"2024-05-30","decision":"2024-07-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add “uveitis” to the list of adverse drug reactions (ADRs) with a frequency “Not known” based on a cumulative review of the MAH safety database and literature. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct the spelling of the active substance ‘alpelisib’ in the SmPC. The RMP version 7.2 has also been submitted."}, {"id":"II/0018","type":"II","opinion":"2023-09-14","decision":"2024-07-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to update drug-drug interaction information, based on final results from study BYL719A2111; this is a phase 1, open-label, fixed-sequence, two-period drug-drug interaction (DDI) study evaluating the PK probe substrates for CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 when administered either alone or in combination with repeated doses of alpelisib. The Annex II and Package Leaflet are updated accordingly. The RMP version 6.0 has also been submitted. In addition, the MAH took the opportunity to update the list of local representatives and to introduce minor editorial changes to the PI."}, {"id":"IAIN/0021/G","type":"IAIN","opinion":"2023-08-25","decision":"2024-07-19","affects":["Annex II","PL"],"codes":["A.4","A.5.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0017","type":"II","opinion":"2023-01-12","decision":"2023-07-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update non-clinical information based on data from two skin toxicology studies conducted in rats: Study 1770766 and Study 1870156."}, {"id":"II/0013","type":"II","opinion":"2022-10-20","decision":"2023-07-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of the SmPC sections 4.6 and 5.3 in order to add fertility data based on studies 2070119 “BYL719: Oral (Gavage) Study of Fertility in the Male Rat” and 2070120 “BYL719: Oral (Gavage) Study of Fertility and Early Embryonic Development in the Female Rat”."}, {"id":"II/0012","type":"II","opinion":"2022-07-21","decision":"2023-07-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to add drug-drug interaction information with CYP3A4 inducers based on Study BYL719A2110, a drug-drug interactions study that evaluated the PK of alpelisib when administered alone or with rifampin, a strong CYP3A4 inducer, in healthy participants."}, {"id":"PSUSA/00010871/202111","type":"PSUSA","opinion":"2022-06-23","decision":"2022-08-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - alpelisib"}, {"id":"N/0006","type":"N","opinion":"2021-09-24","decision":"2022-08-17","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0008/G","type":"II","opinion":"2022-03-24","decision":"2022-08-17","affects":["SmPC","Annex II"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on final results from study CBYL719C2301 (SOLAR-1) listed as a PAES in the Annex II; this is a phase III, randomized, double-blind, placebo controlled study of alpelisib in combination with fulvestrant for men and postmenopausal women with hormone receptor positive, HER2-negative advanced breast cancer which progressed on or after aromatase inhibitor treatment; the Annex II is updated accordingly. In addition, the MAH is updating the ATC code in the SmPC. The RMP version 5.0 has also been submitted."}, {"id":"II/0005/G","type":"II","opinion":"2021-04-22","decision":"2021-05-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add hyperglycaemic hyperosmolar non-ketotic syndrome to the list of adverse drug reactions (ADRs) with frequency \"unknown\" and to update the warning on hyperglycaemia and ketoacidosis based on a review of the safety database. The Package leaflet and Annex II are updated accordingly. The RMP version 4.0 is approved. C.1.4 Update of sections 4.2 and 4.8 of the SmPC to modify the management of hyperglycaemia, rash and diarrhoea and add information about osteonecrosis of the jaw based on the pivotal trial SOLAR-1. The MAH also took the opportunity to make minor editorial changes to the SmPC."}, {"id":"IAIN/0003/G","type":"IAIN","opinion":"2021-01-07","decision":"2021-05-21","affects":["Annex II","PL"],"codes":["B.II.b.2.a","A.5.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "alpelisib__vijoice": { "source": [], "procedures": [] }, "amivantamab__rybrevant": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/rybrevant-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/rybrevant-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/X/0000268898","type":"X","opinion":"2025-12-11","decision":"2026-02-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.c.4.c","B.II.e.7.b","B.I.b.2.e","B.I.a.3.c","B.I.a.1.e","C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to strength, pharmaceutical form and route of administration - (c) change or addition of a new strength/potency; Change in synthesis or recovery of a nonpharmacopoeial excipient (when described in the dossier) or a novel excipient - The excipient is a biological/immunological substance; Change in supplier of packaging components or devices (when mentioned in the dossier) - Replacement or addition of a supplier."}, {"id":"EMA/VR/0000261993","type":"II","opinion":"2025-09-18","decision":"2026-02-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC for Rybrevant and Lazcluze in order to include updated information on enhanced dermatologic management regimen as prophylactic treatment to reduce the risk of dermatological toxicities during treatment, based on results from study 61186372NSC2007. Study 61186372NSC2007 (COCOON) is a Phase 2, open-label, randomized trial evaluating the impact of enhanced versus standard dermatologic management on selected dermatologic adverse events among patients with locally advanced or metastatic EGFR-mutated NSCLC treated first-line with amivantamab + lazertinib. The Package Leaflet is updated accordingly."}, {"id":"PSUSA/00010977/202411","type":"PSUSA","opinion":"2025-06-19","decision":"2025-08-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - amivantamab"}, {"id":"EMA/VR/0000272581","type":"IB","opinion":"2025-06-18","decision":"2025-08-21","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/VR/0000253354","type":"II","opinion":"2025-06-19","decision":"2025-08-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to provide final Overall Survival (OS) data following Rybrevant extension of indication procedure (EMEA/H/C/005454/II/0013), and Lazcluze MAA approval (EMEA/H/C/006074/0000), and based on final results from study 73841937NSC3003 (MARIPOSA); this is a pivotal randomized, open-label, Phase 3 study that compares the efficacy and safety of the combination of amivantamab and lazertinib (Arm A) versus osimertinib monotherapy (Arm B) and lazertinib monotherapy (Arm C) in participants with EGFRm NSCLC."}, {"id":"EMA/VR/0000257307","type":"II","opinion":"2025-05-22","decision":"2025-07-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of sections 4.2 and 4.8 of the SmPC in order to change posology recommendations for the premedication regimen to include a higher and extended dose regimen of oral dexamethasone, in addition to the currently approved labelled 20 mg to reduce the incidence and severity of amivantamab-related infusion related reactions (IRRs), based on results from the SKIPPirr study (61186372NSC2005). This is a Phase 2, proof-of-concept, open label, multicentre study conducted in participants with EGFR exon 19deletion or L858R mutated NSCLC who have progressed on or after prior osimertinib and on or after platinum chemotherapy."}, {"id":"X/0014","type":"X","opinion":"2025-01-30","decision":"2025-04-04","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration"}, {"id":"II/0013","type":"II","opinion":"2024-11-14","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations (EGFRm NSCLC), based on results from study 73841937NSC3003 (MARIPOSA). This is a randomized, open-label, Phase 3 study that compares the efficacy and safety of the combination of amivantamab and lazertinib (Arm A) versus osimertinib monotherapy (Arm B) and lazertinib monotherapy (Arm C) in participants with EGFRm NSCLC."}, {"id":"II/0011","type":"II","opinion":"2024-07-25","decision":"2024-08-22","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include amivantamab in combination with carboplatin and pemetrexed for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 19 deletions or Exon 21 L858R substitution mutations after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI) for RYBREVANT, based on the final results from study 61186372NSC3002 (MARIPOSA 2); this is a randomized, open label, multicenter Phase 3 study that compares efficacy and safety of amivantamab in combination with carboplatin and pemetrexed (ACP) with carboplatin and pemetrexed (CP)."}, {"id":"II/0010","type":"II","opinion":"2024-04-25","decision":"2024-06-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","4.9","5.1","5.2","6.6"],"scope":"Extension of indication to include amivantamab in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with activating epidermal-growth factor receptor (EGFR) Exon 20 insertion mutations for RYBREVANT, based on the final results from study 61186372NSC3001 listed as a Specific Obligation in the Annex II of the Product Information; this is a global, open-label, randomized Phase 3 study of ACP compared to CP alone in participants with newly diagnosed, locally advanced or metastatic NSCLC characterized by EGFR exon 20ins."}, {"id":"IB/0009/G","type":"IB","opinion":"2023-09-20","decision":"2024-05-16","affects":["SmPC","PL"],"codes":["B.I.d.1.a.4","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0005","type":"IB","opinion":"2022-11-29","decision":"2023-09-11","affects":["SmPC","Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0001","type":"II","opinion":"2022-07-07","decision":"2022-09-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of section 4.8 of the SmPC in order to add hypokalaemia and hypomagnesaemia to the list of adverse drug reactions (ADRs), with the frequency common, based on an updated analysis of data submitted during the marketing authorisation procedure. The Package Leaflet is updated accordingly. In addition, the MAH proposed to update the current information in section 4.2 of the SmPC to improve clarity and provide more specific guidance. Section 4.4 was updated to also reflect ILD-like adverse reactions. The MAH also took the opportunity to introduce editorial changes in section 4.8 of the SmPC."} ] }, "apalutamide__erleada": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/erleada-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/erleada-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000323347","type":"IB","opinion":"2026-02-12","decision":"2026-03-26","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"EMA/VR/0000303988","type":"II","opinion":"2026-01-15","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the frequency of the existing ADR ‘Lichenoid eruption’ from ‘not known’ to ‘uncommon’, based on a cumulative safety review. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000296280","type":"II","opinion":"2026-02-26","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2, and 5.2 of the SmPC in order to introduce a dose recommendation for apalutamide in patients with severe hepatic impairment based on the results from Study 56021927PCR1026 listed as a category 3 study in the RMP; this is an open-label, single-dose, multi-center, non-randomized Phase 1 PK study of apalutamide in participants who either had SHI (Child-Pugh Class C) or healthy participants with NHF; the Package Leaflet is updated accordingly. The RMP version 9.1 is considered acceptable. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"EMA/VR/0000319048","type":"II","opinion":"2026-03-12","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to include information regarding apalutamide interference with a digoxin laboratory test based on a cumulative safety review, following the PRAC request in procedure PSUSA/00010745/202502. In addition, the MAH took the opportunity to introduce minor editorial changes and to update the list of local representatives in the Package Leaflet."}, {"id":"EMA/PSUR/0000269021","type":"PSUSA","opinion":"2025-09-18","decision":"2025-11-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"In view of available data on apalutamide and neutropenia as well as agranulocytosis from spontaneous cases with positive dechallenge and/or rechallenge and compatible time to onset, data from clinical trials and in the literature, and in view of a potential mechanism of action, a causal relationship between apalutamide and neutropenia as well as apalutamide and agranulocytosis is at least a reasonable possibility and the product information of apalutamide containing products should be amended accordingly."}, {"id":"IB/0041","type":"IB","opinion":"2025-01-09","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"PSUSA/00010745/202402","type":"PSUSA","opinion":"2024-09-19","decision":"2024-11-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - apalutamide"}, {"id":"N/0039","type":"N","opinion":"2024-07-25","decision":"2024-11-18","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0037","type":"II","opinion":"2024-07-25","decision":"2024-11-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include information on Prostate Specific Antigen (PSA) reduction to undetectable levels, based on results from the TITAN (56021927PCR3002) and SPARTAN (ARN-509-003) studies. TITAN is a Phase 3 randomised, placebo-controlled, double-blind study of Apalutamide Plus Androgen Deprivation Therapy (ADT) versus ADT in subjects with Metastatic Hormone-sensitive Prostate Cancer (mHSPC). SPARTAN is a Phase 3, randomised, double-blind, placebo-controlled study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer. In addition, the MAH took the opportunity to implement a minor QRD change to the Labelling."}, {"id":"II/0036","type":"II","opinion":"2024-04-25","decision":"2024-11-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUSA/00010745/202302","type":"PSUSA","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - apalutamide"}, {"id":"R/0030","type":"R","opinion":"2023-07-20","decision":"2023-09-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"X/0028/G","type":"X","opinion":"2023-06-22","decision":"2023-08-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to add a new strength (240 mg) film-coated tablets grouped with the IB variation (C.I.z). The RMP (version 6.1) has also been submitted. C.I.z (IB): to align the SmPC/PL for Erleada 60 mg with the SmPC/PL proposed for the registration of the new Erleada film-coated tablet strength, 240 mg. The PL for Erleada 60 mg is proposed to be updated to ensure consistency."}, {"id":"PSUSA/00010745/202202","type":"PSUSA","opinion":"2022-10-13","decision":"2022-12-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - apalutamide"}, {"id":"II/0017","type":"II","opinion":"2022-02-10","decision":"2022-12-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of sections 5.3 of the SmPC in order to update non-clinical information based on final results from study TOX11338."}, {"id":"II/0016","type":"II","opinion":"2021-11-18","decision":"2022-12-09","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add Stevens-Johnson Syndrome (SJS) to the list of adverse drug reactions (ADRs) with frequency not known. Cases of SJS were observed in post-marketing data. The Package Leaflet is updated accordingly."}, {"id":"IB/0019","type":"IB","opinion":"2021-11-18","decision":"2022-12-09","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0015","type":"II","opinion":"2021-10-07","decision":"2021-12-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the efficacy, safety information based on final results from study 56021927PCR3002 (TITAN) listed as Letter of Recommendations (11 December 2019, EMEA/H/C/004452/II/0001); this is a double-blind, placebo-controlled, multinational, multicenter Phase 3 study in metastatic castration-sensitive prostate cancer (mCSPC) patients."}, {"id":"II/0013","type":"II","opinion":"2021-06-10","decision":"2021-12-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC in order to update information on pregnancy and update non-clinical information following results of a developmental toxicity study in rats."}, {"id":"II/0009","type":"II","opinion":"2021-02-18","decision":"2021-12-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to include non-clinical information based on final results from a 26-week carcinogenicity study (TOX13540) listed as a category 3 study in the RMP. The RMP version 3.2 is approved"}, {"id":"II/0008","type":"II","opinion":"2021-02-18","decision":"2021-12-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to update efficacy and safety information based on final results from study ARN-509-003 (SPARTAN) listed as a PAES in Annex II; this is a multicenter, randomised, double-blind, placebo-controlled, phase III study of ARN-509 in men with non-metastatic (M0) castration-resistant prostate cancer; the package leaflet and Annex II are updated accordingly. The RMP version 3.1 is approved. In addition, the MAH took the opportunity to update the list of local representatives in the Package leaflet."}, {"id":"II/0007/G","type":"II","opinion":"2020-11-12","decision":"2021-12-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add toxic epidermal necrolysis and decreased appetite to the list of adverse drug reactions (ADRs) with frequency 'not known' and 'very common' respectively based on cumulative safety reviews. In addition, the MAH took the opportunity to make minor corrections in the SmPC, to update the list of local representatives in the Package Leaflet, and to bring the PI in line with the latest QRD template version 10.1."}, {"id":"II/0001","type":"II","opinion":"2019-12-12","decision":"2020-01-27","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) for Erleada based on the results of study 56021927PCR3002 (TITAN study), a randomised, double-blind, placebo-controlled phase 3 study comparing apalutamide plus ADT versus ADT in patients with mHSPC; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated in order to reflect the new indication, to add a warning on ischaemic cardiovascular events and to reflect new safety and efficacy information. The Package Leaflet is updated in accordance."} ] }, "arsenic-trioxide__trisenox": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/trisenox-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/trisenox-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000281747","type":"II","opinion":"2026-01-15","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to update the safety information based on the final results from PASS C18477-ONC-50025 listed as a category 3 study in the RMP; this is an observational Post-Authorisation Long-Term Retrospective Safety Cohort Study of Arsenic Trioxide in First Line Low-to-Intermediate-Risk Acute Promyelocytic Leukaemia (APL) Patients. The updated RMP version 3.0 has also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.4."}, {"id":"EMA/VR/0000314149","type":"IA","opinion":"2025-12-15","decision":null,"affects":["Annex II","PL"],"codes":["A.7","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release"}, {"id":"IB/0080","type":"IB","opinion":"2023-05-25","decision":"2024-05-17","affects":["SmPC","PL"],"codes":["B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished or intermediate product - Other variation"}, {"id":"II/0076","type":"II","opinion":"2022-01-13","decision":"2023-02-03","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC in order to update information on pregnancy and contraception in male patients following the decision and discussion made for EMEA/H/C/PSUSA/00000235/202009 and to add an appropriate period of abstinence for breastfeeding during use of Trisenox. The Package Leaflet is updated accordingly."}, {"id":"IB/0077/G","type":"IB","opinion":"2022-02-22","decision":"2023-02-03","affects":["SmPC","Annex II","PL"],"codes":["B.II.b.2.c.1","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0071","type":"IB","opinion":"2019-11-07","decision":"2020-10-27","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"X/0068","type":"X","opinion":"2019-03-28","decision":"2019-05-27","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"IAIN/0069/G","type":"IAIN","opinion":"2019-01-04","decision":"2019-05-27","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00000235/201709","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - arsenic trioxide"}, {"id":"II/0063/G","type":"II","opinion":"2017-05-05","decision":"2018-04-30","affects":["Annex II","PL"],"codes":["B.II.d.1.c","B.II.d.2.a","B.II.e.2.b","B.II.b.2.c.2","B.II.e.7.b","B.II.d.2.z","B.II.b.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Addition of a new specification parameter to the specification with its corresponding test method; Change in test procedure for the finished product - Minor changes to an approved test procedure; Change in the specification parameters and/or limits of the immediate packaging of the finished product - Addition of a new specification parameter to the specification with its corresponding test method; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing."}, {"id":"IA/0066","type":"IA","opinion":"2017-12-07","decision":"2018-04-30","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0058","type":"II","opinion":"2016-10-13","decision":"2016-11-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of Indication to include induction of remission, and consolidation in adult patients with newly diagnosed low-to-intermediate risk acute promyelocytic leukaemia (APL) (white blood cell count, ≤ 10 x 103/μl) in combination with all trans retinoic acid (ATRA), characterised by the presence of the t(15;17) translocation and/or the presence of the Pro-Myelocytic Leukaemia/Retinoic-Acid-Receptor-alpha (PML/RAR-alpha) gene for Trisenox. As a consequence, sections 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC have been updated and the Package Leaflet has been updated accordingly. A revised version of the RMP (version 1.3) has been approved as part of this application."}, {"id":"T/0052","type":"T","opinion":"2015-01-08","decision":"2015-01-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0049","type":"N","opinion":"2014-01-29","decision":"2014-11-13","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0047","type":"N","opinion":"2013-10-22","decision":"2014-11-13","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0050","type":"IB","opinion":"2014-05-13","decision":"2014-11-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the annexes to QRD version 9. In addition, minor linguistic errors within the translated texts (French, Bulgarian, German, Swedish, Romanian, Danish, Hungarian Greek, Czech, Spanish Estonian, Italian, Finnish, Slovakian Portuguese & Lithuanian) are being corrected."}, {"id":"IAIN/0048","type":"IAIN","opinion":"2013-11-19","decision":"2014-11-13","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0044","type":"T","opinion":"2012-12-12","decision":"2013-01-28","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"MA Transfer from Cephalon Europe to Teva Pharma B.V. Transfer of Marketing Authorisation"}, {"id":"II/0042","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include lymphopenia, headache and increased gamma-glutamyltransferase in the tabulated list of adverse reactions based on the review of safety data collected during a non-Cephalon sponsored study conducted by the Cancer and Leukaemia Group B (CALGB) from 1999 to 2010 (CALGB study C9710). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to include changes to the Package leaflet following the results of user consultation with Target Patient Group (Final report dated 12 August 2011) and to update the list of local representatives in the Package Leaflet."}, {"id":"II/0041","type":"II","opinion":"2011-10-20","decision":"2011-11-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update the product information in line with version 7.3.1 of the QRD template and the SmPC guideline. In addition, a re-analysis of the safety dataset was performed to specify the frequency of adverse drug reactions in section 4.8 of the SmPC. Furthermore, the MAH took the opportunity of this variation to introduce some minor editorial changes to the product information."}, {"id":"S/0036","type":"S","opinion":"2010-05-20","decision":"2010-08-10","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"IB/0037","type":"IB","opinion":"2010-05-11","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"S/0033","type":"S","opinion":"2009-06-25","decision":"2009-09-21","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Seventh Annual reassessment (S/033)"}, {"id":"II/0032","type":"II","opinion":"2009-03-19","decision":"2009-04-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"This type II variation concerns an update of section 4.8 of the SPC with the ADRs 'pancytopenia' and 'differentiation syndrome' reported during post-marketing experience. A differentiation syndrome, like retinoic acid syndrome, has also been reported for the treatment of malignancies other than APL with Trisenox. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make some minor editorial changes to the SPC and the Package Leaflet."}, {"id":"II/0031","type":"II","opinion":"2009-03-19","decision":"2009-04-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"This type II variation concerns an update of sections 4.2, 4.4 and 5.2 of the SPC with further information regarding patients with renal and/or hepatic impairment in line with the results of the pharmacokinetic studies CTI-1064 and CTI-1073, and a general revision of the information on pharmacokinetics in section 5.2 of the SPC for increased clarity. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make some minor editorial changes to the SPC and the Package Leaflet."}, {"id":"S/0029","type":"S","opinion":"2008-05-30","decision":"2008-07-25","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Sixth Annual Reassessment (S/029)"}, {"id":"S/0026","type":"S","opinion":"2007-05-24","decision":"2007-07-23","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"T/0027","type":"T","opinion":"2007-05-02","decision":"2007-06-05","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"R/0021","type":"R","opinion":"2006-12-14","decision":"2007-02-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IA/0022","type":"IA","opinion":"2007-01-17","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"S/0017","type":"S","opinion":"2006-06-01","decision":"2006-07-11","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"T/0016","type":"T","opinion":"2006-03-03","decision":"2006-04-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"S/0015","type":"S","opinion":"2005-06-23","decision":"2005-10-06","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0014","type":"II","opinion":"2005-05-26","decision":"2005-07-04","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","4.9","5.2"],"scope":"The MAH applied for the following changes to the SPC, as requested by the CHMP following the assessment of 3rd and 4th PSURs: Section 4.4, addition of \"Leukocyte Activation Syndrome\"; Section 4.8, update the overall adverse events; Section 4.9, inclusion of the current recommendations for treatment of arsenic overdose (Merck Manual); Section 5.2, inclusion of a statement on in vitro P450 enzyme interactions. The Package Leaflet was updated accordingly. Editorial and spelling corrections have been implemented in the SPC and Package Leaflet."}, {"id":"S/0013","type":"S","opinion":"2004-06-03","decision":"2004-09-09","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"IA/0006","type":"IA","opinion":"2004-02-23","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"IB/0005","type":"IB","opinion":"2004-02-04","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"IA/0004","type":"IA","opinion":"2004-01-07","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"S/0003","type":"S","opinion":"2003-06-26","decision":"2003-10-08","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"I/0001","type":"I","opinion":"2002-04-11","decision":"2002-05-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"} ] }, "asciminib__scemblix": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/scemblix-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/scemblix-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000356235","type":"IB","opinion":"2026-07-31","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["Q.II.b.1.e","Q.II.b.1.b","Q.II.b.1.a","Q.II.b.2.a","Q.II.b.2.c.2","Q.II.b.3.a","Q.II.b.4.b","Q.II.c.1.z","Q.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"E. Administrative Changes - E.5 Deletion of manufacturing sites for an active substance, intermediate or finished product, storage of master and/or working cell bank, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier)."}, {"id":"EMA/VR/0000340759","type":"II","opinion":"2026-06-25","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to add drug-drug interaction information with BCRP and P-gp substrates, based on final results from study CABL001A2112; this is a Phase 1, open-label, 2-period, single-sequence, drug-drug interaction study to assess the effect of asciminib on the pharmacokinetics of digoxin and rosuvastatin in healthy participants."}, {"id":"EMA/X/0000256688","type":"X","opinion":"2026-02-26","decision":"2026-04-23","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension application to introduce a new strength (100 mg film-coated tablets) grouped with a type II variation (C.I.6.a) to add a new indication (treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (Ph+ CML-CP) harbouring the T315I mutation), based on final results from study CABL001X2101 and study CABL001A2004."}, {"id":"EMA/VR/0000287112","type":"IB","opinion":"2025-10-09","decision":"2025-11-17","affects":["Annex II","PL"],"codes":["A.7","B.II.c.1.z","B.II.d.1.z","B.II.b.1.e","B.II.b.2.a","B.II.b.1.b","B.II.b.1.a","B.II.b.2.c.2","B.II.b.3.a","B.II.b.4.b","B.II.d.2.a","B.II.g.4.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change in the specification parameters and/or limits of an excipient - Other changes; Change in the specification parameters and/or limits of the finished product - Change in the specification parameters and/or limits of the finished product to more accurately describe the appearance of the drug product."}, {"id":"EMA/VR/0000265010","type":"II","opinion":"2025-10-16","decision":"2025-11-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a","C.I.4"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"A grouped application consisting of: Extension of indication to include treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) for SCEMBLIX. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated accordingly. RMP version 4.2 has also been submitted. As part of the application the MAH is requesting a 1-year extension of the market protection. Update of sections 4.2, 4.5, 5.1, 5.2 and 5.3 of the SmPC in order to introduce a new posology regimen of 80 mg QD. The Package Leaflet is updated accordingly. RMP version 4.2 has also been submitted."}, {"id":"II/0013/G","type":"II","opinion":"2024-06-13","decision":"2025-07-09","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8","5.1","5.2"],"scope":"Grouped application comprising three type II variations as follows: • C.I.4 - Update of sections 4.5 and 5.2 of the SmPC in order to add drug-drug interaction information with P-gp Substrates based on the final results from studies 2301078, CABL001A2301 and CABL001X2101, listed as a category 3 study in the RMP. • C.I.4 - Update of section 4.8 of the SmPC in order to update the Summary of the safety profile and safety information based on final results from study CABL001A2301 and CABL001X2101 • C.I.4 - Update of section 5.1 of the SmPC in order to update safety information based on final results from study CABL001A2301."}, {"id":"IAIN/0018","type":"IAIN","opinion":"2024-12-04","decision":"2025-07-09","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000248179","type":"II","opinion":"2025-04-25","decision":"2025-07-09","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"A grouped application consisting of: Update of section 4.5 of the SmPC in order to add drug-drug interaction information with OATP1B substrates based on final results from study CABL001A2111; this is a phase 1, open-label, 2-period, single-sequence, drug-drug interaction study to assess the effect of asciminib on the pharmacokinetics of atorvastatin in healthy participants; the Package Leaflet is updated accordingly."}, {"id":"PSUSA/00011008/202310","type":"PSUSA","opinion":"2024-05-30","decision":"2024-07-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - asciminib"}, {"id":"II/0009","type":"II","opinion":"2024-02-29","decision":"2024-07-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update preclinical safety data based on final results from study R1570226: this is a 2-year rat carcinogenicity study. In addition, the MAH took the opportunity to implement editorial changes to the SmPC."}, {"id":"II/0008","type":"II","opinion":"2023-12-14","decision":"2024-07-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to add interaction information between asciminib and OATP1B and BCRP substrates. The Package Leaflet is updated accordingly."}, {"id":"PSUSA/00011008/202210","type":"PSUSA","opinion":"2023-05-25","decision":"2023-07-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - asciminib"}, {"id":"IB/0003","type":"IB","opinion":"2023-03-02","decision":"2023-07-24","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0001","type":"IB","opinion":"2022-12-14","decision":"2023-07-24","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Product Information was updated to add a new pack-size of 180 tablets (multipack) in blister for Scemblix 40 mg film-coated tablet (EU/1/22/1670/005)."} ] }, "atezolizumab__tecentriq": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tecentriq-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tecentriq-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000339687","type":"II","opinion":"2026-06-18","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Anaemia’ to the list of adverse drug reactions (ADRs) with frequency ‘very common’ based on post-marketing data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet, to update the PI in accordance with the latest EMA excipients guideline, to implement editorial changes to the PI. Labelling and PL been added to section 4.8 of the SmPC with the frequency ‘very common’ for atezolizumab monotherapy."}, {"id":"PSUSA/00010644/202505","type":"PSUSA","opinion":"2026-01-29","decision":"2026-03-26","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"EMA/VR/0000290209","type":"II","opinion":"2025-10-16","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"A grouped application comprised of 5 Type II Variations, based on safety reports, as follows: Update of sections 4.4 and 4.8 of the SmPC in order to add ‘uveitis’ in the warning section and to the list of adverse drug reactions (ADRs). Update of section 4.8 of the SmPC in order to add ‘cytomegalovirus infection’ to the list of ADRs with frequency ‘rare’. Update of section 4.8 of the SmPC in order to add ‘tenosynovitis’ to the list of ADRs with frequency ‘uncommon’. Update of section 4.8 of the SmPC in order to add ‘arthritis’ to the list of ADRs with frequency ‘common’. Update of section 4.8 of the SmPC in order to add ‘sarcoidosis’ to the list of ADRs with frequency ‘rare’."}, {"id":"EMA/VR/0000272433","type":"IB","opinion":"2025-06-16","decision":"2026-03-26","affects":["SmPC"],"codes":["B.I.b.1.b","B.II.d.1.a","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of an active substance, starting material / intermediate / reagent used in the manufacturing process of the active substance - Tightening of specification limits; Change in the specification parameters and/or limits of the finished product - Tightening of specification limits; Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/VR/0000262253","type":"II","opinion":"2025-06-05","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to amend an existing warning on infusion-related reactions with anaphylaxis based on Drug safety report No. 1135433; the Package Leaflet is updated accordingly. The RMP version 32.1 is also agreed. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template version."}, {"id":"EMA/VR/0000245137","type":"II","opinion":"2025-03-27","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ''Peripheral neuropathy'' to the list of adverse drug reactions (ADRs) of atezolizumab monotherapy with frequency ''common'', as well as, to add Immune thrombocytopenia to the existing ADR Thrombocytopenia of atezolizumab monotherapy and combination therapy based on post-marketing data and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template version 10.4."}, {"id":"EMA/VR/0000315105","type":"II","opinion":"2026-03-12","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"A grouped application consisting of: Update of section 4.4 of the SmPC to enhance the text to explicitly advise healthcare professionals to monitor for signs of Immune-mediated myocarditis/myositis/myasthenia gravis overlap syndrome based on postmarketing data. The Package Leaflet is updated accordingly. The RMP version 33.0 has also been submitted. Update of section 4.8 of the SmPC to add hypoalbuminemia, hypophosphatemia, hypocalcaemia, and gamma-glutamyltransferase increased as adverse drug reactions for atezolizumab based on postmarketing data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to the SmPC."}, {"id":"PSUSA/00010644/202405","type":"PSUSA","opinion":"2025-01-30","decision":"2025-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"II/0088","type":"II","opinion":"2024-09-19","decision":"2025-03-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of Sections 4.8 and 5.1 of the SmPC in order to add “Xerosis” and “blood creatine phosphokinase increased” to the list of adverse drug reactions (ADRs) with frequency “common” and “uncommon” respectively and update the efficacy information based on the final disease-free survival (DFS) results and second interim overall survival (OS) results from study GO29527 (IMpower010); this is a phase III, open-label, randomized study to investigate the efficacy and safety of atezolizumab (Anti-PD-L1 Antibody) compared with best supportive care following adjuvant cisplatin-based chemotherapy in patients with completely resected stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC); the Package…"}, {"id":"II/0087","type":"II","opinion":"2024-12-12","decision":"2025-03-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of sections 4.2 in order to include information regarding switching treatment between Tecentriq intravenous and subcutaneous (and vice versa), based on primary results from study MO43576 (IMscin002); this is a phase II, randomised, multicenter, open-label cross-over study to evaluate participants and healthcare professional reported reference for subcutaneous atezolizumab compared with intravenous atezolizumab formulation in participants with non-small cell lung cancer. The package leaflet has been revised accordingly. The RMP version 31.2 is agreed. In addition, the MAH took the opportunity to introduce minor formatting changes to the PI."}, {"id":"II/0084","type":"II","opinion":"2024-04-11","decision":"2024-08-26","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘hypophysitis’ to the list of adverse drug reactions (ADRs) with frequency ‘uncommon’ based on interim results from study WO39391 (IMpassion030). This is a Phase III, randomized, open label study comparing atezolizumab in combination with adjuvant anthracycline/taxane-based chemotherapy versus chemotherapy alone in patients with operable triple-negative breast cancer; the package leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to the SmPC, labelling and package leaflet."}, {"id":"II/0083/G","type":"II","opinion":"2024-02-08","decision":"2024-08-26","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study IMvigor210 (GO29293) listed as a PAES in the Annex II; this is a Phase II, multicenter, single-arm study of atezolizumab in patients with locally advanced or metastatic urothelial bladder cancer. The Annex II is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and to update section 3 of the SmPC with information on pH and osmolality to bring it in line with the latest QRD template and SmPC guideline. C.I.13: Submission of the final report from study SAUL (MO29983) listed as a category 3 study in the RMP."}, {"id":"II/0082","type":"II","opinion":"2024-07-25","decision":"2024-08-26","affects":["SmPC"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) who are ineligible for platinum-based therapy (see section 5.1 for selection criteria), for TECENTRIQ, based on final results from study MO29872 (IPSOS); this is a phase 3, open-label, multicenter, randomised study to investigate the efficacy and safety of atezolizumab compared with chemotherapy in patients with treatment naive advanced or recurrent (stage IIIB not amenable for multimodality treatment) or metastatic (stage IV) NSCLC who are deemed unsuitable for platinum-containing therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated."}, {"id":"IB/0085/G","type":"IB","opinion":"2024-07-04","decision":"2024-08-26","affects":["Annex II"],"codes":["A.4","B.I.a.2.a","B.I.a.4.c","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Change to in-process tests or limits applied during the manufacture of the AS - Deletion of a non-significant in-process test; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0086/G","type":"IAIN","opinion":"2024-06-28","decision":"2024-08-26","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010644/202305","type":"PSUSA","opinion":"2023-12-14","decision":"2024-02-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"X/0076","type":"X","opinion":"2023-11-09","decision":"2024-01-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration"}, {"id":"II/0078","type":"II","opinion":"2023-08-31","decision":"2024-01-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the final overall survival (OS) analysis results based on final results from study WO30070 listed as a PAES in the Annex II; this is a Phase III, multicenter, randomized, placebo-controlled study of atezolizumab as monotherapy and in combination with platinum-based chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma. Annex II of the SmPC has also been updated to remove the PAES as it has now been fulfilled. The RMP version 27.1 is agreed."}, {"id":"II/0077/G","type":"II","opinion":"2023-04-26","decision":"2023-05-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Three new adverse reactions were included: Facial paresis Grouped application comprising two type II variations as follows:"}, {"id":"II/0075","type":"II","opinion":"2023-01-26","decision":"2023-02-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add ‘pericardial disorders’ to the list of adverse drug reactions (ADRs) with frequency common in monotherapy and uncommon in combination therapy based on the final results from Drug Safety Report (DSR 1115896) including review of available clinical trial data, post-marketing data, and literature. In addition, the MAH took the opportunity to update Annex II section D of the SmPC to refer to immune-mediated adverse reactions and to implement editorial changes in the SmPC. The Package Leaflet was updated accordingly. The RMP version 23.1 has also been agreed."}, {"id":"PSUSA/00010644/202205","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"IB/0071","type":"IB","opinion":"2022-07-25","decision":"2023-02-09","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex II has been revised to amend the due date for the provision of a final study report."}, {"id":"II/0064","type":"II","opinion":"2022-04-22","decision":"2022-06-07","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include adjuvant treatment of non-small cell lung cancer (NSCLC) following resection and platinum-based chemotherapy for adult patients whose tumours have PD-L1 expression on ≥ 50% of tumour cells (TC) for Tecentriq as monotherapy based on the results from the pivotal phase III Study GO29527 (IMpower010); as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. Minor editorial changes have been made throughout the SmPC. The Package Leaflet is updated in accordance. Version 21.2 of the RMP has also been submitted."}, {"id":"R/0069","type":"R","opinion":"2022-02-24","decision":"2022-04-25","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010644/202105","type":"PSUSA","opinion":"2021-12-16","decision":"2022-02-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"N/0063","type":"N","opinion":"2021-08-12","decision":"2022-02-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0067","type":"II","opinion":"2021-12-02","decision":"2022-02-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of section 4.8 of the SmPC in order to include the new ADR of rhinorrhoea for atezolizumab in combination therapy, as part of the grouped term of nasopharyngitis identified in the IMpassion031 study and reviewed in the context of a drug safety report. The package leaflet is proposed to be updated accordingly. Additional amendments are proposed to the footnotes of ADRs in the SmPC, the removal of the term ‘lung infection’, the inclusion of the term ‘orthostatic hypertension’ and the inclusion of a new footnote listing the preferred terms covered for the ADR of psoriasis."}, {"id":"IAIN/0068","type":"IAIN","opinion":"2021-09-29","decision":"2022-02-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0061","type":"II","opinion":"2021-07-08","decision":"2021-08-20","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of an updated RMP version 20.0 in order to add severe cutaneous adverse reactions (SCARs) as an important identified risk and its associated risk minimisation measures, a DHPC, following the addition of SCARS to the Tecentriq PI with procedure EMEA/H/C/004143/II/0054. In addition the MAH has also taken the opportunity to update the due dates of final CSR of two Post-authorisation efficacy studies."}, {"id":"II/0060","type":"II","opinion":"2021-07-22","decision":"2021-08-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to harmonise the atezolizumab posology regimen of 840 mg every 2 weeks, 1200 mg every 3 weeks and 1680 mg every 4 weeks administered as an IV infusion across the currently authorised indications of NSCLC, ES-SCLC, TNBC and HCC, based on PK modelling and simulation data. As a consequence of the harmonized dose schedules, the MAH is applying for a combined SmPC and PL. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to include minor editorial changes to the PI."}, {"id":"II/0058","type":"II","opinion":"2021-05-06","decision":"2021-08-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the updated efficacy results from study YO40245 (IMbrave150) with a data cut-off of 31 August 2020 as recommended by the CHMP in the context of variation EMEA/H/C/004143/II/0039; IMbrave 150 is a Phase III, open-label, multicenter, randomized, two-arm pivotal study designed to evaluate the efficacy and safety of atezolizumab + bevacizumab versus sorafenib in patients with locally advanced or metastatic hepatocellular carcinoma who had not received prior systemic treatment."}, {"id":"II/0033","type":"II","opinion":"2021-03-25","decision":"2021-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours express PD-L1 for Tecentriq based on the results of the pivotal study GO29431 (IMpower110), comparing atezolizumab monotherapy to platinum-based chemotherapy. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated accordingly. The RMP version 12.0 has also been submitted."}, {"id":"II/0030","type":"II","opinion":"2021-03-18","decision":"2021-04-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to reflect the outcome of anti-drug antibody (ADA) analyses conducted across studies POPLAR, OAK, IMpower 150, IMpower 130, IMPower 131, IMpower 132, IMvigor 211, IMmotion 151, IMpower 133 and IMpassion 130, further to the CHMP recommendation."}, {"id":"II/0054","type":"II","opinion":"2021-02-25","decision":"2021-03-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add severe cutaneous adverse reactions (SCARs) to the list of adverse drug reactions (ADRs) with frequency uncommon, based on the review of safety data presented in a drug safety report (DSR 1105724); the Package Leaflet is updated accordingly. A direct health care professional communication (DHPC) is also proposed to communicate on this risk. In addition, the MAH took the opportunity to add the term pemphigoid to the description of rash in Section 4.8 of the SmPC. The MAH also took the opportunity to update minor typographical errors in the SmPC and PL."}, {"id":"IB/0056","type":"IB","opinion":"2021-02-23","decision":"2021-03-31","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010644/202005","type":"PSUSA","opinion":"2021-01-28","decision":"2021-03-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"II/0051","type":"II","opinion":"2021-01-14","decision":"2021-03-26","affects":["Annex II"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product"}, {"id":"II/0050","type":"II","opinion":"2020-12-10","decision":"2021-03-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect efficacy results based on the final OS analysis from study WO29522 (IMpassion130) comparing atezolizumab in combination with nab-paclitaxel with placebo with nab-paclitaxel for patients with previously untreated metastatic triple-negative breast cancer."}, {"id":"II/0048","type":"II","opinion":"2021-01-14","decision":"2021-03-26","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Submission of the results of study WO41486 evaluating the effectiveness of the HCP brochure designed to mitigate important immune-related risks in patients receiving atezolizumab in the European Union. As a consequence, the MAH is updating section 4.4 of the SmPC, Annex II.D and the RMP. In addition, the MAH is proposing a delay in the due date for the submission of the CSR for IMvigor210 to 31 August 2021."}, {"id":"II/0047","type":"II","opinion":"2020-09-03","decision":"2020-10-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add headache, dry skin and blood creatinine increased to the list of adverse drug reactions (ADRs) for atezolizumab given as monotherapy identified in study WO29636. The MAH has taken this opportunity to update the frequencies of existing ADRs in section 4.8 subsections 'Summary of the safety profile' and 'Description of selected adverse reactions' to reflect the updated pool of patients for atezolizumab monotherapy. Other minor corrections and editorial changes are being proposed. The package leaflet is updated accordingly."}, {"id":"II/0039","type":"II","opinion":"2020-09-17","decision":"2020-10-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include, in combination with with bevacizumab, the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy, based on the results of the pivotal study YO40245 (IMbrave150) as well as data from Arms A and F of the supportive Phase Ib study GO30140. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the Tecentriq 1200mg concentrate for solution for infusion SmPC are updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1"}, {"id":"II/0036","type":"II","opinion":"2020-07-23","decision":"2020-10-27","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Submission of the final report from study GO28915 (OAK) listed as a category 3 study in the RMP. This is a Phase III, open-label multicentre, randomized study to investigate the efficacy and safety of atezolizumab (anti−PD-L1 antibody) compared with docetaxel in patients with NSCLC after failure with platinum-containing chemotherapy. In addition, section 4.8 of the SmPC is updated to reflect available information regarding the potential relationship of ADA and safety based on an integrated analyses of studies IMvigor210, IMvigor211, OAK, POPLAR, IMpower150, IMpower130, IMpower131, IMpower132, IMpower133 and IMpassion130."}, {"id":"PSUSA/00010644/201911","type":"PSUSA","opinion":"2020-06-25","decision":"2020-08-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"II/0040","type":"II","opinion":"2020-04-17","decision":"2020-08-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to include the adverse drug reactions (ADRs) hyperthyroidism with a “common” frequency and hypertension with a “very common” frequency for atezolizumab used in combination with chemotherapy, as identified in study IMvigor130. The MAH took the opportunity of this variation to add preferred terms (PTs) to the footnotes to the ADR table in section 4.8 of the SmPC. The package leaflet is proposed to be updated accordingly."}, {"id":"II/0035","type":"II","opinion":"2020-02-13","decision":"2020-08-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to reflect the results of study GO29664 (iMATRIX) evaluating the safety and pharmacokinetics of Tecentriq in paediatric (<18, n=69) and young adult patients (18-30 years, n=18) with relapsed or progressive solid tumours as well as with Hodgkin's and non-Hodgkin's lymphoma. This study was agreed under the Paediatric Investigational Plan EMEA-001638-PIP01-14-M02 (EMA decision: P/0207/2019). The Package Leaflet is updated accordingly."}, {"id":"II/0034","type":"II","opinion":"2020-02-13","decision":"2020-08-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include updated overall survival data from study IMvigor 211 (GO29294), a phase III study to investigate the efficacy and safety of atezolizumab compared with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer after failure of platinum-containing chemotherapy."}, {"id":"II/0032","type":"II","opinion":"2020-01-16","decision":"2020-08-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SmPC in order to include blood alkaline phosphatase increased and blood creatinine increased as common and alopecia as very common adverse drug reactions for atezolizumab given in combination with other medicinal products based on the review of safety data from a pooled population. In addition, the instruction for treatment interruption due to neutropenia and peripheral neuropathies, when atezolizumab is used in combination with nab-paclitaxel in metastatic triple negative breast cancer, is being revised to only recommend interruption of nab-paclitaxel in section 4.4 of the SmPC."}, {"id":"IB/0031","type":"IB","opinion":"2020-02-10","decision":"2020-08-19","affects":["SmPC","PL"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"IAIN/0046","type":"IAIN","opinion":"2020-06-19","decision":"2020-08-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0028","type":"II","opinion":"2019-07-11","decision":"2019-09-03","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC with new ADRs identified in IMpower132 study. This change is supported by safety data as presented in a drug safety report referring to the IMpower132 safety report (report 1089805) previously submitted to the Agency. The package leaflet is updated accordingly."}, {"id":"II/0019","type":"II","opinion":"2019-07-25","decision":"2019-09-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of Indication to include Tecentriq, in combination with nab-paclitaxel and carboplatin, indicated for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR mutant or ALK-positive NSCLC; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. RMP version 9.1 has been accepted."}, {"id":"II/0018","type":"II","opinion":"2019-07-25","decision":"2019-09-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include, in combination with carboplatin and etoposide, first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) for tecentriq; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP version 9.1 has been agreed."}, {"id":"X/0017","type":"X","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new"}, {"id":"PSUSA/00010644/201811","type":"PSUSA","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"II/0022","type":"II","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.1","4.2","5.1","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to add 2 dosing regimens, 840 mg every 2 weeks and 1680 mg every 4 weeks administered as an IV infusion for the approved indications, based on results of population pharmacokinetics modelling and simulation analyses (report No. 1085557) and supported by exposure-response analyses (report No. 1087176). Consequential changes are made to sections 4.1, 4.2 and 5.1 of the 840 mg strength SmPC in line with the existing urothelial cancer and lung cancer indications. The package leaflet is updated accordingly."}, {"id":"II/0024","type":"II","opinion":"2019-05-29","decision":"2019-07-08","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4, and 4.8 of the SmPC regarding the risk of immune-related myositis identified during a comprehensive analysis of patients treated with Tecentriq. The additional risk minimisations in Annex 2D, the Package Leaflet and the RMP (final version v11.1) are updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2019-05-02","decision":"2019-07-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include new ADRs identified in IMmotion150 and IMmotion151 studies. The revision of the list of ADRs is supported by a drug safety report reflecting the ADRs in the updated pool of patients for monotherapy (n=3178) and combination therapy (n=1345). The Package Leaflet is updated accordingly."}, {"id":"IB/0026","type":"IB","opinion":"2019-05-25","decision":"2019-07-08","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"II/0007/G","type":"II","opinion":"2019-01-31","decision":"2019-03-05","affects":["SmPC","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.2","6.6"],"scope":"Extension of indication to include in combination with bevacizumab, paclitaxel and carboplatin the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC), based on the interim results of study GO29436 (IMpower 150). As a consequence sections 4.1, 4.2, 4.4, 4.8, 5.1, 6.2 and 6.6 of the SmPC are updated. In addition update of section 4.8 of the SmPC in order to update the monotherapy safety data and reflect the largest pooled monotherapy population available (now including also data from IMvigor211 and PCD4989g studies). The Package Leaflet and the RMP (version 4.2) are updated in accordance."}, {"id":"PSUSA/00010644/201805","type":"PSUSA","opinion":"2018-12-13","decision":"2019-02-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - atezolizumab"}, {"id":"N/0015","type":"N","opinion":"2018-08-09","decision":"2019-02-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0004","type":"II","opinion":"2018-06-14","decision":"2019-02-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC in order to update the safety information based on the primary results from study IMvigor211 in order to fulfil ANX 002. This is a phase III, open-label, multicentre, randomized study to investigate the efficacy and safety of atezolizumab (anti- PD-L1 antibody) compared with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer after failure with platinum-containing chemotherapy. The annex II.D, the Package Leaflet and the RMP (version 3.2, according to GVP module V revision 2) are updated accordingly. Some editorial changes throughout the Product Information are also made."}, {"id":"II/0010","type":"II","opinion":"2018-05-31","decision":"2018-07-02","affects":["SmPC"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","5.1"],"scope":"Update of sections 4.1, 4.2 and 5.1 of the SmPC in order to restrict the ‘treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are considered cipsplatin ineligible’ indication by including ‘and whose tumours have a PDL-1 expression ≥ 5%’, based on the review of interim analysis data by the independent data monitoring committee (IDMC) from study IMvigor 130 (WO30070) listed as a PAES in the Annex II; this is a Phase III, multicentre, randomized, placebo-controlled study of atezolizumab administered as monotherapy or in combination with platinum-based chemotherapy compared with platinum-based chemotherapy in patients with untreated locally advanced or…"}, {"id":"II/0002/G","type":"II","opinion":"2018-02-22","decision":"2018-04-04","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add myocarditis as a new adverse reaction, based on the results of a cumulative review of cases of suspected myocarditis provided in the drug safety report number 1080476. Consequently, the information regarding posology and special warnings have been updated. The Annex II and the Package Leaflet have been updated accordingly. The RMP version 2.1 has also been updated."}, {"id":"T/0006","type":"T","opinion":"2018-02-20","decision":"2018-03-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0003/G","type":"IB","opinion":"2017-11-10","decision":"2018-03-07","affects":["SmPC","Labelling","PL"],"codes":["B.I.d.1.a.4","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "avapritinib__ayvakyt": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ayvakyt-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ayvakyt-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000348944","type":"II","opinion":"2026-09-17","decision":"2026-10-16","affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC in order to update information on paediatrics based on final results from study BLU-285-3101 (ROVER); this is a Phase 1/2, open label, single arm study evaluating the safety, pharmacokinetics, and anti tumour activity of avapritinib in paediatric patients with advanced solid tumours dependent on KIT or PDGFRA signalling."}, {"id":"EMA/VR/0000275571","type":"II","opinion":"2025-11-27","decision":"2026-07-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to add drug-drug interaction information with CYP3A substrates based on the final results from study BLU-285-1107 listed as a category 3 study in the RMP. This is a drug-drug interaction study to investigate the effect of 300 mg once daily avapritinib on the pharmacokinetics (PK) of midazolam in patients with unresectable or metastatic Gastrointestinal Stromal Tumors (GIST) and other Advanced Solid Tumors. The MAH also updated PBPK model to extend the clinical findings of Study BLU-285-1107 and simulate the effects of lower doses of avapritinib on the pharmacokinetics of midazolam and its metabolite."}, {"id":"IB/0033","type":"IB","opinion":"2024-04-17","decision":"2024-07-26","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0023","type":"II","opinion":"2023-11-09","decision":"2023-12-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","4.9","5.1","5.2","5.3"],"scope":"Extension of indication to include for avapritinib treatment of adult patients with indolent systemic mastocytosis (ISM) with moderate to severe symptoms inadequately controlled on symptomatic treatment based on results from the pivotal part of study BLU-285-2203 (PIONEER), this is a 3-part, randomized, double-blind, placebo-controlled, Phase 2 study to evaluate safety and efficacy of avapritinib (BLU-285) in indolent and smoldering systemic mastocytosis with symptoms inadequately controlled with standard therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 4.9, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0022","type":"II","opinion":"2023-04-26","decision":"2023-05-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to change posology recommendations and to update pharmacokinetic information for use in patients with severe hepatic impairment based on the final results from study BLU-285-0107 listed as a category 3 study in the RMP; this is a phase 1, open-label, single-dose study to investigate the influence of severe hepatic impairment on the pharmacokinetics of avapritinib. The package leaflet is updated accordingly. The RMP version 3.1 has also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3."}, {"id":"IB/0024","type":"IB","opinion":"2023-03-13","decision":"2023-05-26","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":["6.3"],"scope":"Product information section 6.3 is updated to reflect the shelf-life extension of the finished product AYVAKYT 100 mg, 200 mg and 300 mg film-coated tablets (EU/1/20/1473/001-003) as packaged for sale from 3 years to 4 years."}, {"id":"IB/0020/G","type":"IB","opinion":"2022-10-04","decision":"2023-05-26","affects":["SmPC"],"codes":["B.II.f.1.z","B.II.b.3.z","B.II.f.1.b.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation; Change in the manufacturing process of the finished or intermediate product - Other variation; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Administrative change - Deletion of manufacturing sites"}, {"id":"II/0014","type":"II","opinion":"2022-05-12","decision":"2022-07-15","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"C.I.11.b - Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required Submission of the final report from study BLU-285-1101 listed as a Specific Obligation in the Annex II of the Product Information. This is an interventional Phase 1 study, designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of avapritinib administered orally in patients with unresectable GIST or other relapsed or refractory solid tumours."}, {"id":"X/0004/G","type":"X","opinion":"2022-01-27","decision":"2022-03-24","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"R/0007","type":"R","opinion":"2021-05-20","decision":"2021-07-23","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0003/G","type":"II","opinion":"2021-03-25","decision":"2021-07-23","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.d.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in the specification parameters and/or limits of the finished product - Change outside the approved specifications limits range"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2020-10-15","decision":"2021-07-23","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "avelumab__bavencio": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/bavencio-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/bavencio-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000314741","type":"II","opinion":"2026-04-10","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"A grouped application comprised of 2 Type II Variations, as follows: Update of section 4.4 of the SmPC in order to update the warning on ‘immune mediated adverse reactions’, particularly regarding myositis, myocarditis, and myasthenia gravis (Triple-M syndrome), based on a safety review. The Package Leaflet is updated accordingly. avelumab in combination with axitinib with frequency ‘not known’, based on a safety review. The Package Leaflet is updated accordingly. The RMP version 9.3 has been submitted. In addition, the MAH took the opportunity to introduce alignment changes to the PI."}, {"id":"EMA/VR/0000279701","type":"II","opinion":"2025-11-27","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘cytokine release syndrome’ to the list of adverse drug reactions (ADRs) with frequency uncommon, based on a safety assessment report. In addition, the MAH took the opportunity to introduce updates to the PI that include warning on polysorbate as well as statements on the use of the Patient Card in addition to administrative and editorial changes to the PI."}, {"id":"EMA/VR/0000261861","type":"II","opinion":"2025-11-27","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add “Gastritis” to the list of adverse drug reactions (ADRs) with frequency “Not known” based on postmarketing data and literature. The Package Leaflet is updated accordingly. The RMP version 9.1 has also been submitted."}, {"id":"II/0051","type":"II","opinion":"2025-03-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add “neutropenia” to the list of adverse drug reactions (ADRs) with frequency “not known” based on post marketing data and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the PI in accordance with the latest EMA excipients guideline."}, {"id":"R/0050","type":"R","opinion":"2025-01-30","decision":"2025-03-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0044/G","type":"II","opinion":"2024-07-11","decision":"2025-03-12","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.b","A.6","C.I.z","C.I.12"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Grouped application comprising four variations as follows: Type II (C.I.11.b): To update Annex II and the RMP version 7.1 for Bavencio to change the classification of “safety in patients with autoimmune disease” to the important identified risk “other immune mediated adverse reactions” along with removal of the patient information brochure from the educational material, following the PRAC assessment report PSUSA/00010635/202303."}, {"id":"IAIN/0045/G","type":"IAIN","opinion":"2024-06-10","decision":"2025-03-12","affects":["SmPC","PL"],"codes":["C.I.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a Union referral procedure - The product is not covered by the defined scope of the procedure"}, {"id":"II/0046/G","type":"II","opinion":"2025-02-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8"],"scope":"A grouped application consisting of: C.I.4: Update of sections 4.2, 4.4, 4.6 and 4.8 of the SmPC in order to add the immune-mediated adverse reactions sclerosing cholangitis, arthritis, polymyalgia rheumatica, and Sjogren’s syndrome based on post-marketing data and literature. The Package Leaflet is updated accordingly. The RMP version 7.3 has also been submitted. C.I.4: Update of section 4.8 of the SmPC in order to update the immunogenicity information based on results from studies EMR100070-003, B9991003 and 100/B9991001. Study EMR100070-003 is a Phase 2, single-arm, open label, multicenter study to investigate the clinical activity and safety of avelumab in patients with mMCC."}, {"id":"PSUSA/00010635/202303","type":"PSUSA","opinion":"2023-11-09","decision":"2024-01-05","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - avelumab"}, {"id":"II/0035","type":"II","opinion":"2022-09-15","decision":"2023-03-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC based on final results from study MS100070-0306 following a P46 procedure (EMEA/H/C/004338/P46/009). This is a Phase I, multi-centre, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in paediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumours (including central nervous system tumours) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy."}, {"id":"IB/0038","type":"IB","opinion":"2022-12-15","decision":"2023-03-21","affects":["SmPC"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IA/0034","type":"IA","opinion":"2022-04-21","decision":"2023-03-21","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00010635/202103","type":"PSUSA","opinion":"2021-11-11","decision":"2022-01-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - avelumab"}, {"id":"II/0028","type":"II","opinion":"2021-10-14","decision":"2022-01-06","affects":["SmPC"],"codes":["B.II.d.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"The SmPC section 3 has been updated as follows: The osmolality is between 285 and 350 mOsm/kg."}, {"id":"IB/0022","type":"IB","opinion":"2020-12-21","decision":"2022-01-06","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IAIN/0030","type":"IAIN","opinion":"2021-10-12","decision":"2022-01-06","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0018","type":"II","opinion":"2020-12-10","decision":"2021-01-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include a new indication for Bavencio in the treatment as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum based chemotherapy; as a consequence, sections 4.1 , 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 5.0 of the RMP has also been submitted. The MAH took also the occasion to include some editorial changes in the PI."}, {"id":"II/0015","type":"II","opinion":"2020-07-23","decision":"2020-09-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to change posology recommendations, amend an existing warning and add new ADRs with frequency uncommon regarding myasthenia gravis and myasthenic syndrome. The update results from an update of the Company Core Data Sheet (CCDS) based on the review of cases of myasthenia gravis/myasthenic syndrome. The Package Leaflet is updated accordingly. The RMP version 2.2 has also been submitted to reclassify \"Other immune-related events (myasthenic syndrome)” from an important potential risk to an important identified risk of “Other immune-related events (myasthenia gravis/myasthenic syndrome)\"."}, {"id":"II/0013","type":"II","opinion":"2020-05-28","decision":"2020-08-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information following results from study EMR100070-003 Part B listed as a specific obligation in the Annex II; this is a Phase II, open-label, multicenter trial to investigate the clinical activity and safety of avelumab (MSB0010718C) in subjects with Merkel cell carcinoma. With this submission the company is also taking the opportunity to update annex-II proposing deletion of the specific obligation and proposing the switch from conditional to full marketing authorisation. The package leaflet and the RMP (version 2.1) are updated accordingly."}, {"id":"II/0009/G","type":"II","opinion":"2019-09-19","decision":"2019-10-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include first-line combination treatment with avelumab and axitinib in adult patients with advanced renal cell carcinoma (aRCC) for Bavencio; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, section 4.2 of the SmPC is updated in order to introduce a switch of the avelumab dosing regimen from 10 mg/kg every two weeks (weight-based) to a flat dose of 800 mg every two weeks, both for the newly proposed indication aRCC and the already existing indication of Merkel cell carcinoma (MCC)."}, {"id":"R/0008","type":"R","opinion":"2019-04-26","decision":"2019-06-20","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010635/201809","type":"PSUSA","opinion":"2019-04-26","decision":"2019-06-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - avelumab"}, {"id":"R/0003","type":"R","opinion":"2018-06-28","decision":"2018-08-31","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"T/0004","type":"T","opinion":"2018-06-14","decision":"2018-07-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IA/0001","type":"IA","opinion":"2017-12-13","decision":"2018-07-02","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "axicabtagene-ciloleucel__yescarta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/yescarta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/yescarta-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000350867","type":"IAIN","opinion":"2026-06-08","decision":null,"affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.) - Implementation of the agreed wording"}, {"id":"EMA/VR/0000308229","type":"II","opinion":"2026-04-23","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.7","6.4"],"scope":"Update of sections 4.2, 4.4, 4.5. 4.7 and 6.4 of the SmPC in order to modify the pre- and post-infusion monitoring recommendations and requirements related to the risk of CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome) based on data from clinical trials, post-marketing experience and literature. The Package Leaflet is updated accordingly. The RMP version 8.0 for Tecartus and RMP version 13.0 for Yescarta have also been submitted. In addition, Annex II has been updated accordingly."}, {"id":"EMA/VR/0000309793","type":"II","opinion":"2026-02-26","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.c"],"outcome":"accepted","kind":"other","sections":["6.4"],"scope":"The SmPC section 6.4 has been updated as follows: Yescarta/Tecartus must be stored at ≤ -120 ̊C and must remain frozen until the patient is ready for treatment to ensure viable live autologous cells are available for patient administration. The Labelling and PL have been updated accordingly."}, {"id":"EMA/VR/0000285857","type":"II","opinion":"2025-11-13","decision":null,"affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a reference statement to current institutional / national guidelines for the monitoring and management of CRS, neurologic events and ICANS. In addition, the MAH took the opportunity to introduce clarification and administrative updates across the PI, including Annex II."}, {"id":"EMA/VR/0000255932","type":"II","opinion":"2025-07-24","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Updated accordingly."}, {"id":"PSUSA/00010703/202410","type":"PSUSA","opinion":"2025-05-22","decision":"2025-07-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - axicabtagene ciloleucel"}, {"id":"WS/2632","type":"WS","opinion":"2024-04-25","decision":"2024-11-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to update the safety monitoring timelines based on data from clinical studies, postmarketing studies, and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to other sections of the SmPC to align the language across both products."}, {"id":"II/0065","type":"II","opinion":"2023-12-14","decision":"2024-11-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add Infusion Related Reactions to the list of adverse drug reactions (ADRs) with frequency Common, based on a cumulative review of the MAH safety database, clinical trials and postmarketing data. The Package Leaflet is updated accordingly."}, {"id":"II/0063","type":"II","opinion":"2023-11-09","decision":"2024-11-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include new clinical data based on Overall Survival (OS) Primary Analysis from study KTE-C19-107 (ZUMA-7); this is a phase 3, randomized, open-label study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in subjects with relapsed/refractory diffuse large B cell lymphoma (DLBCL) in the 2nd line setting. In addition, the MAH took the opportunity to include the date of the latest renewal in section 9 and to submit a consolidated Environmental Risk Assessment (ERA) document."}, {"id":"IG/1781","type":"IG","opinion":"2024-08-14","decision":"2024-11-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0071","type":"IAIN","opinion":"2024-02-22","decision":"2024-11-14","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0056","type":"R","opinion":"2023-05-25","decision":"2023-07-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0058","type":"N","opinion":"2023-01-17","decision":"2023-07-24","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0046","type":"II","opinion":"2022-09-15","decision":"2022-10-14","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) for Yescarta; as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 8.0 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the product information with minor editorial changes."}, {"id":"PSUSA/00010703/202110","type":"PSUSA","opinion":"2022-06-23","decision":"2022-08-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - axicabtagene ciloleucel"}, {"id":"II/0042","type":"II","opinion":"2022-04-22","decision":"2022-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy. Consequently, sections 4.1, 4.8, 5.1 and 5.2 of the SmPC and Package Leaflet are proposed to be updated. As a consequence, the RMP (version 7.0) has been updated to align with the indication extension. In addition, the applicant has taken the opportunity to make minor editorial corrections throughout the SmPC and package leaflet."}, {"id":"II/0028","type":"II","opinion":"2021-04-22","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC on cytokine release syndrome (CRS) and neurologic adverse reaction grading and management and update of section 5.1 of the SmPC to include data from 36-month and 48-month analyses from ZUMA-1 study Cohorts 1 and 2. The Package leaflet is updated accordingly. In addition, other minor updates are included in the product information. The RMP (version 3.5) has been updated accordingly."}, {"id":"II/0021","type":"II","opinion":"2020-05-28","decision":"2020-11-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the SmPC, Annex II, package leaflet and RMP to change the dose of tocilizumab to one dose instead of four doses in order to manage the Cytokine Release Syndrome. In addition, treatment centres should have access to an additional dose within 8 hours of each previous dose. Additional changes to the SmPC have been made with regards to the wording on GMO requirements."}, {"id":"IB/0020","type":"IB","opinion":"2020-06-11","decision":"2020-11-25","affects":["Annex II"],"codes":["B.II.g.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IB/0013","type":"IB","opinion":"2019-12-10","decision":"2020-11-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.g.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IAIN/0023","type":"IAIN","opinion":"2020-06-22","decision":"2020-11-25","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"IA/0022","type":"IA","opinion":"2020-05-11","decision":"2020-11-25","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"PSUSA/00010703/201904","type":"PSUSA","opinion":"2019-11-14","decision":"2020-01-13","affects":["SmPC","Labelling"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - axicabtagene ciloleucel"}, {"id":"II/0003","type":"II","opinion":"2019-04-26","decision":"2019-10-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"In the 24-month follow-up analysis of study ZUMA-1 and based on the mITT population (results from an independent review committee), the Objective Response Rate and the Complete Response rate were 74% and 54%, respectively. The median time to response was 1.0 months (range: 0.8 to 12.2 months). The Duration of Response was longer in patients who achieved Complete Response compared to patients with a best response of Partial Response. Of the 55 patients who achieved CR, 7 patients had SD and 10 had PR at their initial tumour assessment and converted to CR as late as 12 months after YESCARTA infusion. Median duration of response and median overall survival have not been reached."}, {"id":"IB/0002","type":"IB","opinion":"2019-01-14","decision":"2019-10-21","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0001","type":"IAIN","opinion":"2018-10-19","decision":"2019-10-21","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "axitinib__inlyta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/inlyta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/inlyta-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000245212","type":"IAIN","opinion":"2025-01-21","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"IA/0032","type":"IA","opinion":"2021-08-20","decision":"2022-09-21","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IAIN/0028","type":"IAIN","opinion":"2019-10-31","decision":"2020-12-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0029","type":"IB","opinion":"2020-10-29","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010022/201901","type":"PSUSA","opinion":"2019-09-19","decision":"2019-11-11","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - axitinib"}, {"id":"PSUSA/00010022/201801","type":"PSUSA","opinion":"2018-09-20","decision":"2018-11-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - axitinib"}, {"id":"T/0024","type":"T","opinion":"2018-07-11","decision":"2018-08-03","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"R/0021","type":"R","opinion":"2017-03-23","decision":"2017-05-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0004","type":"N","opinion":"2013-07-04","decision":"2017-05-22","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH applied to include the contact details for Croatia to the list of local representatives. Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0020","type":"IAIN","opinion":"2016-06-09","decision":"2017-05-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0014","type":"N","opinion":"2015-06-24","decision":"2016-05-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0013","type":"II","opinion":"2015-05-21","decision":"2016-05-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC and relevant section of the Package Leaflet following a safety update of the Core Data Sheet."}, {"id":"II/0008","type":"II","opinion":"2014-05-22","decision":"2014-11-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to delete the information on CYP1A2 induction by smoking further results of a population pharmacokinetic modelling analysis of the evaluation of the effect of smoking on axitinib pharmacokinetics."}, {"id":"II/0007","type":"II","opinion":"2014-05-22","decision":"2014-11-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add \"cardiac failure events\" as a new adverse drug reaction reported with a frequency “common” following a routine review of the MAH's safety database. The Package Leaflet is proposed to be updated accordingly. The MAH also took the opportunity to make minor editorial changes to the SmPC and Package leaflet."}, {"id":"II/0003/G","type":"II","opinion":"2013-10-24","decision":"2014-11-07","affects":["SmPC","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of section 4.8 of the SmPC in order to include glossodynia as an adverse reaction. In addition section 4.8 of the SmPC has been updated with the frequencies of the adverse drug reactions as it was requested by the CHMP further to the assessment of the PSUR 1. The MAH took also the opportunity to make minor changes in section 4.8 based on the post marketing experience. Finally the MAH made one minor change in section 4.2 of the SmPC. The Package Leaflet was updated accordingly."}, {"id":"X/0001","type":"X","opinion":"2013-06-27","decision":"2013-08-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"This line extension introduces two additional tablet strengths 3mg and 7 mg of axitinib in addition to the currently approved 1mg and 5 mg tablets. The proposed maximum clinical dose is 10 mg twice daily. The two additional strengths are intended to simplify dosing for patients who need dose modification up or down from the starting dose of 5 mg twice daily."} ] }, "belantamab-mafodotin__blenrep": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/blenrep-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf-0"], "procedures": [ {"id":"EMA/VR/0000362446","type":"IB","opinion":"2026-08-26","decision":null,"affects":["SmPC"],"codes":["C.z"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"To update section 4.2 of the SmPC to correct a discrepancy between the SmPC and the DREAMM-7/DREAMM-8 registration study protocols regarding the BCVA change criteria used to guide dose modifications. In addition, the MAH took the opportunity to include the date of first authorisation in Section 9 of the SmPC and introduced a change to Section 4.2 of the DE SmPC to improve readability, without altering the meaning of the sentence."}, {"id":"EMA/VR/0000314500","type":"II","opinion":"2026-02-05","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on Interim Analysis 3 (IA3) results for the DREAMM-8 study (Study Number 207499). This is a phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (B-Pd) versus pomalidomide plus bortezomib and dexamethasone (PVd) in participants with relapsed/refractory multiple myeloma (RRMM). In addition, the MAH took the opportunity to introduce clarifying changes to the PI."}, {"id":"EMA/VR/0000314494","type":"II","opinion":"2026-02-05","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to update pharmacokinetic information based on final results from study 209626 (DREAMM-12). This is a phase I study to evaluate the pharmacokinetics and safety of belantamab mafodotin monotherapy in participants with relapsed and/or refractory multiple myeloma (RRMM) who have normal and varying degrees of impaired renal function."}, {"id":"EMA/N/0000291577","type":"N","opinion":"2025-09-01","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Package Leaflet to enhance clarity and urgency of safety information, ensure terminology is consistent with the SmPC and patient-friendly, streamline reconstitution instructions by removing redundancies and aligning with SmPC guidance and revise details of local representatives."} ] }, "belzutifan__welireg": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/welireg-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000347680","type":"II","opinion":"2026-10-01","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update preclinical safety information based on final results from rat carcinogenicity study MK-6482. In addition, the MAH took the opportunity to implement editorial changes to the PI."}, {"id":"EMA/VR/0000349497","type":"II","opinion":"2026-09-03","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.9","5.2"],"scope":"Update of sections 4.5, 4.9 and 5.2 of the SmPC in order to update information when administering WELIREG to patients who are dual UGT2B17 and CYP2C19 poor metabolizers and to update information regarding overdose, based on results from study P018V01MK6482 (LITESPARK-018). This is a Phase 1, dose-escalation study to evaluate safety and tolerability of belzutifan in participants with advanced clear cell renal cell carcinoma (ccRCC). In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI."}, {"id":"EMA/R/0000290222","type":"R","opinion":"2025-11-13","decision":"2026-01-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation"} ] }, "bevacizumab__avastin": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/avastin-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/avastin-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000316070","type":"IB","opinion":"2026-01-12","decision":null,"affects":["Annex II"],"codes":["A.7","B.I.a.4.b","B.I.b.1.b","B.II.d.1.a","B.II.d.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change to in-process tests or limits applied during the manufacture of the active substance - Addition of a new in-process test and limits; Change in the specification parameters and/or limits of an active substance, starting material / intermediate / reagent used in the manufacturing process of the active substance - Tightening of specification limits."}, {"id":"EMA/VR/0000263392","type":"IB","opinion":"2025-04-25","decision":"2025-12-18","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update SmPC section 2, 4,4 and 6,1 to include information on excipient content (Polysorbate 20), according to the Excipients guidance. The package leaflet is updated accordingly. In addition, the MAH has taken the opportunity to make minor editorial corrections throughout the annexes. In addition, the MAH took the opportunity to update the details of the local representatives in BE, LU, MT."}, {"id":"EMA/VR/0000245353","type":"IB","opinion":"2025-02-21","decision":"2025-12-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.I.a.2.a","A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the active substance - Minor change in the manufacturing process of the active substance; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)."}, {"id":"EMA/PSUR/0000274402","type":"PSUSA","opinion":"2025-10-16","decision":"2025-12-18","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"In view of available data on hyaline occlusive glomerular microangiopathy reported in the literature, including in some cases a positive de-challenge and in view of a plausible mechanism of action, the PRAC considers a causal relationship between bevacizumab and hyaline occlusive glomerular microangiopathy is at least a reasonable possibility. The PRAC concluded that the product information of products containing bevacizumab should be amended accordingly."}, {"id":"N/0130","type":"N","opinion":"2023-03-14","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00000403/202202","type":"PSUSA","opinion":"2022-10-13","decision":"2022-12-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bevacizumab"}, {"id":"IB/0129/G","type":"IB","opinion":"2022-07-01","decision":"2022-12-16","affects":["SmPC","PL"],"codes":["B.I.d.1.a.4","B.II.d.1.a","B.I.d.1.c","B.I.b.2.e","B.II.d.2.d","B.II.f.1.b.1","A.7","B.II.f.1.e","B.I.a.4.b","B.I.b.1.b","B.I.a.4.c","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Change in the specification parameters and/or limits of the finished product - Tightening of specification limits; Stability of AS - Change in the re-test period/storage period or storage conditions - Change to an approved stability protocol; Change in test procedure for AS or starting material/reagent/intermediate - Other changes to a test procedure (including replacement or addition) for the AS or a starting material/intermediate."}, {"id":"N/0123","type":"N","opinion":"2021-08-10","decision":"2022-01-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0125","type":"IB","opinion":"2021-09-14","decision":"2022-01-31","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0118","type":"IB","opinion":"2021-01-08","decision":"2022-01-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0105","type":"N","opinion":"2018-08-09","decision":"2020-04-03","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0110","type":"II","opinion":"2020-01-16","decision":"2020-04-03","affects":["Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study NEJ026 listed as an obligation in the Annex II of the Product Information. This is an open-label, randomized, Phase III study conducted in Japan to compare erlotinib + bevacizumab combination therapy versus erlotinib monotherapy as first-line therapies for patients with NSCLC with EGFR gene mutations (exon 19 deletion or exon 21 L858R substitution). The RMP version 31.0 has also been agreed. In addition, the Package leaflet is updated to reflect information on sodium content in compliance with the revised Annex to the European Commission guideline on \"Excipients in the labelling and package leaflet of medicinal products for human use\"."}, {"id":"II/0106/G","type":"II","opinion":"2019-04-26","decision":"2020-04-03","affects":["SmPC","Annex II"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0112","type":"IB","opinion":"2020-02-25","decision":"2020-04-03","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IAIN/0111","type":"IAIN","opinion":"2019-10-30","decision":"2020-04-03","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"T/0100","type":"T","opinion":"2018-02-20","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0093","type":"II","opinion":"2017-01-26","decision":"2017-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"4.2 Posology and method of administration Paediatric population The safety and efficacy of bevacizumab in children less than 18 years old have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made. There is no relevant use of bevacizumab in the paediatric population in the indications for treatment of cancers of the colon, rectum, breast, lung, ovarian, fallopian tube, peritoneum, cervix and kidney. 4.8 Undesirable effects Paediatric population The safety and efficacy of Avastin in children less than 18 years old have not been established."}, {"id":"II/0092","type":"II","opinion":"2017-04-21","decision":"2017-06-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of Indication to include the use of Avastin in combination with paclitaxel and carboplatin for the for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated with efficacy and safety information from study GOG-0213. The Package Leaflet and RMP (v. 27.1) are updated in accordance."}, {"id":"II/0091","type":"II","opinion":"2016-09-15","decision":"2017-06-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 of the SmPC in order to update the safety and efficacy, pharmacokinetic information based on the results of paediatric study (BO20924) conducted in children and adolescents presenting with rhabdomyosarcoma (RMS) or non RMS soft tissue sarcoma (NR-STS). As a consequence, section 5.2 has been updated to include pharmacokinetic information resulting from 4 paediatric studies using a population pharmacokinetic model as per the study’s objective."}, {"id":"II/0089","type":"II","opinion":"2016-04-28","decision":"2016-06-02","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include safety information derived from the phase III study GO25632. In addition, Annex II of the product information is updated as the condition on the investigation of suitable biomarkers to allow identification and selection of a more targeted population (ANX 068) is removed from the list of post authorisation measures. Consequently, the RMP v.26 is updated."}, {"id":"II/0087","type":"II","opinion":"2015-10-22","decision":"2016-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to amend the existing warning and safety information on increased serum creatinine levels, with or without proteinuria, associated with Avastin use. The Package Leaflet is updated accordingly."}, {"id":"II/0086","type":"II","opinion":"2016-04-28","decision":"2016-06-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1"],"scope":"Extension of indication to include the combination of bevacizumab with erlotinib for the first line treatment of patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) activating mutations. As a consequence, sections 4.1, 4.2, 4.5, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet and RMP (v.26.0) are updated in accordance."}, {"id":"II/0082","type":"II","opinion":"2015-07-23","decision":"2016-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2 and 4.8 of the SmPC to include information regarding non-mandibular osteonecrosis in children. In addition, the MAH took the opportunity to update section 4.4 of the SmPC with the inclusion of an instruction to record the batch number to improve drug traceability. The Package Leaflet is updated accordingly."}, {"id":"II/0080","type":"II","opinion":"2015-02-26","decision":"2015-03-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","4.8","5.3"],"scope":"Update of sections 4.6, 4.8 and 5.3 of the SmPC in order to update the safety information regarding the risk of foetal abnormalities based on post-marketing data. In addition, information related to adverse reactions reported in the post-marketing setting in section 4.8 of the SmPC is re-arranged in line with the SmPC guideline. The RMP is updated in order to re-classify embryo-foetal developmental disturbance as an identified risk."}, {"id":"II/0072","type":"II","opinion":"2015-02-26","decision":"2015-03-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix for Bevacizumab in combination with paclitaxel and cisplatin or paclitaxel and topotecan. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC have been updated. The Package Leaflet is updated in accordance."}, {"id":"R/0068","type":"R","opinion":"2014-09-25","decision":"2014-11-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0074","type":"II","opinion":"2014-09-25","decision":"2014-11-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0063","type":"II","opinion":"2014-06-26","decision":"2014-07-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include Avastin in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents. As a consequence of this new indication, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC have been updated. The Package Leaflet is updated accordingly."}, {"id":"II/0066","type":"II","opinion":"2014-02-20","decision":"2014-06-30","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with the results from the final analysis from study AVF4095g. Annex II has been updated accordingly in order to remove the condition on the final analysis for Overall Survival from study AVF4095g. The requested variation proposed amendments to the Summary of Product Characteristics and Annex II."}, {"id":"II/0065","type":"II","opinion":"2014-04-25","decision":"2014-06-30","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with the final results from study BO17707. Annex II has been updated accordingly in order to remove the condition on the final analysis for Overall survival from study BO17707."}, {"id":"II/0064","type":"II","opinion":"2014-05-22","decision":"2014-06-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0061","type":"II","opinion":"2013-09-19","decision":"2014-06-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC on diabetes as a risk factor for developing arterial thromboembolic events following review of the MAH's safety database. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet with the addition of the Croatian representative. Furthermore, the PI is being brought in line with the latest QRD template (version 9.0) and minor editorial changes were made. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"IB/0060","type":"IB","opinion":"2013-07-02","decision":"2014-06-30","affects":["SmPC"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Revision of a warning in SmPC section 4.4 regarding the potential risk of systemic adverse events following intravireal injection of anti-VEGF treatments."}, {"id":"II/0058/G","type":"II","opinion":"2013-04-25","decision":"2013-05-27","affects":["SmPC","PL"],"codes":["C.I.4","C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with the addition of information on necrotising fasciitis. The Package Leaflet has been updated accordingly. In addition section 4.8 of the SmPC has been updated to add the incidence of gastrointestinal perforations in metastatic renal cell cancer patients."}, {"id":"II/0057","type":"II","opinion":"2013-02-21","decision":"2013-05-27","affects":["SmPC","Annex II"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of Annex II of the PI in order to remove the condition on the biomarkers for VEGF-A from studies BO177007 and GOG-218. In addition the MAH took the opportunity to make some editorial changes to the SmPC."}, {"id":"II/0056/G","type":"II","opinion":"2013-02-21","decision":"2013-05-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b","C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SmPC with regards to wound healing complications further to the request of the CHMP in the assessment of the 9th PSUR. In addition, a warning in section 4.4 of the SmPC has been included in relation to traceability of the medicinal product. The MAH has taken the opportunity to correct an error in the package leaflet in the description of pulmonary embolisms and to introduce minor editorial corrections in the SmPC and PL. Furthermore, the PI is being brought in line with the latest QRD template version 8.3."}, {"id":"II/0053","type":"II","opinion":"2012-11-15","decision":"2013-05-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to add efficacy and safety data further to the completion of study ML18147 (a phase III study of Avastin plus crossover fluoropyrimidine-based chemotherapy in patients with mCRC). This variation application addresses post-authorisation measure 041. In addition the MAH took the opportunity to make some editorial changes to the SmPC and PL."}, {"id":"II/0046","type":"II","opinion":"2012-09-20","decision":"2012-10-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"II/0044","type":"II","opinion":"2012-07-19","decision":"2012-08-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to revise the wording on the adverse reactions that have been reported from unauthorised intravitreal use of Avastin based on recently published clinical trials."}, {"id":"II/0051","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with the final overall survival data from study GOG-0218 (Post authorisation measure). The Annex II is updated in accordance."}, {"id":"II/0047/G","type":"II","opinion":"2012-02-16","decision":"2012-03-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of section 5.1 of the SmPC with the results from two studies in children aged > 3 years old with relapsed or progressive high-grade glioma. In addition, section 4.2 of the SmPC has been updated to include a statement that Avastin should not be used in children aged 3 years to less than 18 years with recurrent or progressive high-grade glioma."}, {"id":"II/0048","type":"II","opinion":"2011-12-15","decision":"2012-02-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8"],"scope":"Update of section 4.5 of the SmPC to include safety information on the interaction between bevacizumab and anti-EGFR treatments in the mCRC indication and section 4.8 of the SmPC to clarify that part of the cases of Microangiopathic Haemolytic Anaemia (MAHA)/Thrombotic Microangiopathy (TMA) occur in patients who are not treated with sunitinib further to the assessment of the PSURs 7 and 8. The requested variation proposed amendments to the SmPC."}, {"id":"II/0042","type":"II","opinion":"2011-11-17","decision":"2011-12-19","affects":["Annex II"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Additional site for the manufacture of the active substance"}, {"id":"II/0041","type":"II","opinion":"2011-11-17","decision":"2011-12-19","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include the use of Avastin, in combination with carboplatin and paclitaxel for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Consequently, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC have been updated to reflect the change in the indication. The Risk Management Plan and the Package Leaflet have been updated accordingly. In addition, a minor change was made to the Labelling."}, {"id":"II/0045","type":"II","opinion":"2011-10-20","decision":"2011-11-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to include gall bladder perforation as requested by the CHMP further to the assessment of FUM 066. The PL has been updated accordingly. Finally the MAH took the opportunity to make minor changes in section 4.4 of the SmPC to clarify the wording on thromboembolic events and in section 4.8 of the SmPC to update the wording on Central Nervous System (CNS) haemorrhage."}, {"id":"II/0043/G","type":"II","opinion":"2011-06-23","decision":"2011-07-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8"],"scope":"Update of sections 4.4, 4.6 and 4.8 of the Summary of Product Characteristics (SmPC) to include ovarian failure observed in NSABP C-08 study. The PL has been updated accordingly. In addition to this, the wording on congestive heart failure (CHF) in section 4.8 of the SmPC has been revised to include an increased incidence of CHF with a cumulative doxorubicin dose greater than 300 mg/m2 observed in BO20603 study. Finally, the MAH made a minor change in section 4.8 of the SmPC in order to reflect better the System Organ Class (SOC) of osteonecrosis of the jaw."}, {"id":"II/0033","type":"II","opinion":"2011-05-19","decision":"2011-06-29","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"To extend the indication to the use of Avastin in combination with capecitabine for first-line treatment of patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline-containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Avastin in combination with capecitabine. For further information about HER2 status, refer to section 5.1. Consequently, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC have been updated to reflect the change in the indication accordingly."}, {"id":"II/0040","type":"II","opinion":"2011-01-20","decision":"2011-03-24","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to revise the wording on proteinuria and arterial thromboembolic events further to the assessment of the 7th PSUR."}, {"id":"A20/0038","type":"A20","opinion":"2010-12-15","decision":"2011-02-28","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Review of all available data on the combination of Avastin with either paclitaxel or docetaxel for the treatment of first-line metastatic breast cancer, particularly the results of the AVF3694g study and its impact on the benefit-risk balance."}, {"id":"II/0039","type":"II","opinion":"2010-11-18","decision":"2010-12-20","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to include information on cases of osteonecrosis of jaw (ONJ) associated with co-administration with bevacizumab and bisphosphonates further to the assessment of the FUM 65. The PL has been updated accordingly."}, {"id":"II/0037","type":"II","opinion":"2010-10-21","decision":"2010-11-26","affects":["SmPC","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the Summary of Product Characteristics to include wording on increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia (including some fatalities) which have been observed mainly in patients treated with platinum- or taxane-based therapies in the treatment of NSCLC and mBC as requested by the CHMP further to the assessment of FUM 63. In addition, the Labelling has been updated to replace ''batch'' by ''lot''. Finally the MAH took the opportunity to correct some typographical errors in the SmPC."}, {"id":"II/0036","type":"II","opinion":"2010-07-22","decision":"2010-08-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to include a warning on adverse reactions reported following unapproved intravitreal use with Avastin. This proposed update results from a safety review conducted by the Marketing Authorisation Holder (MAH). The Package Leaflet has been updated accordingly. Based on a safety review of ocular events after off-label intravitreal/intraocular Avastin use, performed by the MAH it has been concluded by the CHMP that information on eye disorders from unapproved intravitreal use should be included as a safety warning in section 4.4 of the SmPC."}, {"id":"II/0035/G","type":"II","opinion":"2010-05-20","decision":"2010-07-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8","5.1","5.2"],"scope":"Update of section 4.4 of the Summary of Product Characteristics (SmPC) to amend the wording regarding neutropenia and infections as requested by the CHMP further to the assessment of the renewal procedure. In addition, section 4.8 of the SmPC has been updated to include wording on gastrointensinal ulcer based on a safety review conducted by the MAH. The Package Leaflet has been updated accordingly. Furthermore, sections 4.2 and 4.6 of the SmPC have been updated in accordance with the latest QRD template (version 7.3.1, March 2010) and sections 4.2, 4.8, 5.1 and 5.2 of the SmPC have been updated in accordance with the SmPC guideline (revision 2, September 2009)."}, {"id":"II/0034","type":"II","opinion":"2010-04-22","decision":"2010-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to include information on risks of hypersensitivity reactions and infusions reactions related to the administration of bevacizumab. This update results from a safety review on the issue conducted by the MAH. The PL has been updated accordingly."}, {"id":"R/0031","type":"R","opinion":"2009-10-22","decision":"2009-12-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IA/0032","type":"IA","opinion":"2009-07-31","decision":null,"affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing site"}, {"id":"II/0030","type":"II","opinion":"2009-06-25","decision":"2009-07-23","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5","5.1","5.2"],"scope":"Update of SPC section 4.5 to include information on Avastin in combination with interferon alpha 2a or in combination with chemotherapies, update of section 5.1 to remove text no longer relevant concerning study BO17704 and to include the results of the final overall survival analysis from study BO17705 and update of section 5.2 with information of distribution and elimination based on availability of completed studies."}, {"id":"II/0024","type":"II","opinion":"2009-06-25","decision":"2009-07-23","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the indication for the treatment of metastatic breast cancer in combination with paclitaxel or docetaxel."}, {"id":"II/0026","type":"II","opinion":"2009-04-23","decision":"2009-05-29","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Additional site for the manufacture of the drug substance. Tightening of drug substance and drug product specifications."}, {"id":"N/0029","type":"N","opinion":"2009-04-08","decision":null,"affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0025","type":"II","opinion":"2009-02-19","decision":"2009-03-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.3","4.4","4.8","5.1"],"scope":"Update to section 4.3 \"Contraindications\", and section 4.4 \"Special Warnings and Precautions for Use\", section 4.8 \"Undesirable Effects\" to remove the contraindication in patients with untreated CNS metastases and section 5.1 \"Pharmacodynamic Properties\" to include the results of the final overall survival analysis from BO17704 study and the results of the retrospective independent radiological review of tumour assessments from BO17705 study in order to fulfil relevant post-approval commitments. The Package Leaflet has been updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2008-07-24","decision":"2008-08-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5","4.8"],"scope":"Update of section 4.5 \"Interactions with other medicinal products and other forms of interaction\" to include information on Microangiopathic hemolytic anaemia cases with unapproved combination of Avastin with sunitinib and section 4.8 \"Undesirable effects\" of the SPC to include the terms \"dysphonia\" and \"renal thrombotic microangiopathy\". Editorial changes and corrections have been implemented. The Package Leaflet has been updated accordingly."}, {"id":"II/0020","type":"II","opinion":"2008-01-24","decision":"2008-02-26","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"The MAH applied to update the summary of product characteristics following the fulfilment of follow-up measures: Section 4.2. and Section 5.2 were revised following the results of a PK study in a limited number of paediatric patients; Section 5.1 was revised with the updated results from study E2100 in metastatic breast cancer. The text under 5.1 referring to the mechanism of action of bevacizumab is revised to provide more detailed information. Furthermore, in Section 4.8 \"pulmonary hypertension\" was added and the incidence of venous thromboembolic events was revised."}, {"id":"II/0014","type":"II","opinion":"2007-12-13","decision":"2008-01-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to use Avastin in combination with fluoropyrimidine-based chemotherapy for treatment of patients with metastatic carcinoma of the colon or rectum. The MAH took the opportunity to implement editorial changes to the Package Leaflet as a result of the user testing procedure."}, {"id":"II/0015","type":"II","opinion":"2007-11-15","decision":"2007-12-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include Avastin in combination with interferon alfa-2a for first line treatment of patients with advanced and/or metastatic renal cell cancer."}, {"id":"II/0019","type":"II","opinion":"2007-09-20","decision":"2007-10-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","6.6"],"scope":"Update of the SPC Sections 4.4 and 4.8 to include information relating to fistulae cases and section 6.6 to clarify instructions on the dilution of bevacizumab solution for infusion. The Package Insert is also updated accordingly."}, {"id":"II/0016","type":"II","opinion":"2007-09-20","decision":"2007-10-24","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) to the manufacturing process for the active substance"}, {"id":"II/0009","type":"II","opinion":"2007-07-19","decision":"2007-08-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"\"Avastin, in addition to platinum-based chemotherapy, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.\""}, {"id":"II/0013","type":"II","opinion":"2007-03-22","decision":"2007-04-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of SPC sections 4.4 and 4.8 with information on neutropenia, congestive heart failure, pulmonary haemorhage/ haemoptysis; section 4.8 to include a statement on venous thromboembolic events and to consolidate safety information. The Package Leaflet was revised accordingly. Minor editorial changes were also introduced in the SPC and Package Leaflet."}, {"id":"II/0008","type":"II","opinion":"2007-02-22","decision":"2007-03-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"\"Avastin in combination with paclitaxel for first-line treatment of patients with metastatic breast cancer\". The MAH has also updated the Package Leaflet to include the Romanian and Bulgarian contact details in the list of local representatives."}, {"id":"IA/0011","type":"IA","opinion":"2007-01-12","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0007","type":"II","opinion":"2006-06-01","decision":"2006-07-04","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with addition of information on Reversible Posterior Leukoencephalopathy Syndrome (RPLS) and hypertensive encephalopathy, update of information on gastrointestinal perforations. In addition, Section 4.8 has been revised to clarify the wording regarding tumour-associated haemorrhage, to address a request from the CHMP, following the review of the 1st PSUR and to include information on rare cases of nasal septum perforation. The Package Leaflet is also revised accordingly, where relevant. In addition, contact details of the local representatives in the Patient Leaflet have been updated."}, {"id":"II/0003","type":"II","opinion":"2005-11-17","decision":"2005-12-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the SPC in section 4.8 and section 4 of the PL to include adverse events reported in study AVF2192g regarding congestive heart failure and elderly patients and for the implementation of the latest QRD template."}, {"id":"IA/0004","type":"IA","opinion":"2005-11-08","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"} ] }, "bexarotene__targretin": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/targretin-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/targretin-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IG/1263","type":"IG","opinion":"2020-06-24","decision":"2021-06-21","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IG/1260/G","type":"IG","opinion":"2020-06-24","decision":"2021-06-21","affects":["SmPC","Labelling","PL"],"codes":["A.1","A.5.a","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"IA/0060","type":"IA","opinion":"2021-05-12","decision":"2021-06-21","affects":["SmPC","Annex II","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IA/0059/G","type":"IA","opinion":"2021-03-02","decision":"2021-06-21","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"IG/1008","type":"IG","opinion":"2018-11-30","decision":"2019-11-07","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0050","type":"T","opinion":"2018-08-30","decision":"2018-09-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0048","type":"N","opinion":"2017-11-15","decision":"2018-06-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0042","type":"N","opinion":"2015-08-31","decision":"2018-06-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"A31/0043","type":"A31","opinion":"2018-03-22","decision":"2018-06-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Pursuant to Article 31 of Directive 2001/83/EC, the United Kingdom triggered on 7 July 2016 a referral resulting from pharmacovigilance data, and requested the PRAC to review the routine risk minimisation in place for the oral and topical retinoids to ensure the available data and the risks associated with the adverse teratogenic effects and neuropsychiatric disorders are accurately and consistently addressed within the product information where appropriate and justified by data."}, {"id":"PSUSA/00000404/201409","type":"PSUSA","opinion":"2015-03-26","decision":"2015-05-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bexarotene"}, {"id":"N/0040","type":"N","opinion":"2014-10-09","decision":"2015-04-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0039","type":"N","opinion":"2014-06-03","decision":"2015-04-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0031","type":"N","opinion":"2012-04-25","decision":"2015-04-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH revised the list of local representatives contact details. Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0033","type":"II","opinion":"2013-02-21","decision":"2015-04-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to add information on pharmacokinetics in special populations. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI is being brought in line with the latest QRD template version 8.3."}, {"id":"IA/0028","type":"IA","opinion":"2009-04-06","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"IA/0027","type":"IA","opinion":"2009-02-05","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in BR/QC testing - repl./add. manuf. responsible for BR - not incl. BC/testing"}, {"id":"N/0026","type":"N","opinion":"2008-10-14","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0025","type":"II","opinion":"2008-07-24","decision":"2008-08-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of or change(s) to the pharmaceutical documentation"}, {"id":"II/0023","type":"II","opinion":"2007-11-15","decision":"2007-12-11","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"This type II variation was submitted by the MAH upon request by the CHMP following the assessment of FU2 006.2, and concerns an update of section 4.5 of the SPC with information regarding combination with CYP3A4 substrates with a narrow therapeutic margin. In the absence of detailed information, caution must be advised in case of combination with CYP3A4 substrates having a narrow therapeutic margin i.e. immunosuppressive agents (ciclosporine, tacrolimus, sirolimus) as well as CYP3A4-metabolised cytotoxics, i.e. cyclophosphamide, etoposide, finasteride, ifosfamide, tamoxifen, vinca-alcaloïds."}, {"id":"T/0022","type":"T","opinion":"2007-03-16","decision":"2007-04-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IA/0021","type":"IA","opinion":"2006-12-20","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"IB/0016","type":"IB","opinion":"2006-07-04","decision":null,"affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"R/0015","type":"R","opinion":"2006-02-23","decision":"2006-04-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0014","type":"N","opinion":"2005-10-28","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0013","type":"N","opinion":"2005-02-11","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0012","type":"N","opinion":"2004-11-26","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0011","type":"N","opinion":"2004-09-29","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0007","type":"N","opinion":"2004-06-14","decision":null,"affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0006","type":"IA","opinion":"2004-03-23","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"N/0005","type":"N","opinion":"2003-05-15","decision":"2003-06-04","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0002","type":"II","opinion":"2002-06-27","decision":"2002-10-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"I/0003","type":"I","opinion":"2002-06-11","decision":"2002-07-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"} ] }, "binimetinib__mektovi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/mektovi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/mektovi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000241083","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.2"],"scope":"Update of section 4.2 and 5.2 of the SmPC in order to update paediatric information following PIP compliance check (EMEA-C-001588-PIP01-13- M03 and EMEA-C-001454-PIP03-15-M03). In addition, the MAH took the opportunity to implement a minor correction in section 4.8 of the SmPC."}, {"id":"WS/2658","type":"WS","opinion":"2024-11-14","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of sections 5.1 of the SmPC in order to update efficacy and safety information following the outcome of procedures 004579/0000 and R/0024 based on final results from study C4221004 (CMEK162B2301). This was a 2-part, multi-center, randomized, open label, Phase III study comparing the efficacy and safety of encorafenib plus binimetinib to vemurafenib and encorafenib monotherapy in participants with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"WS/2538","type":"WS","opinion":"2024-07-25","decision":"2024-08-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include binimetinib in combination with encorafenib for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600E mutation for MEKTOVI and BRAFTOVI based on results from study PHAROS (Study ARRAY-818-202) at the primary completion date; this is a Phase II, open-label, multicentre, non-comparative study (interventional). As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the Braftovi SmPC and sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the Mektovi SmPC are updated. The Package Leaflet is updated in accordance. Version 3.0 of Braftovi and Mektovi RMPs have also been approved."}, {"id":"X/0029","type":"X","opinion":"2024-04-25","decision":"2024-06-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to add a new strength of 45 mg (film-coated tablets)."}, {"id":"PSUSA/00010717/202306","type":"PSUSA","opinion":"2024-01-25","decision":"2024-03-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - binimetinib"}, {"id":"R/0024","type":"R","opinion":"2023-04-26","decision":"2023-06-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0020","type":"IAIN","opinion":"2022-01-24","decision":"2022-06-21","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"IA/0016","type":"IA","opinion":"2021-08-09","decision":"2022-06-21","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IA/0013","type":"IA","opinion":"2021-06-08","decision":"2022-06-21","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"WS/1695","type":"WS","opinion":"2020-04-30","decision":"2020-04-30","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include encorafenib in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, who have received prior systemic therapy, as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP version 2.0 is acceptable. Furthermore, the PI is brought in line with the latest QRD template version 10.1. Note: The MAH in the course of the assessment withdrew Mektovi (binimetinib) from the applied indication. Therefore, the extension of indication only concerns the product Braftovi (encorafenib)."}, {"id":"IB/0001","type":"IB","opinion":"2018-10-30","decision":"2019-10-24","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IAIN/0005/G","type":"IAIN","opinion":"2019-08-08","decision":"2019-10-24","affects":["SmPC","Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.c.1","B.II.e.7.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in supplier of packaging components or devices (when mentioned in the dossier) - Replacement or addition of a supplier"} ] }, "blinatumomab__blincyto": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/blincyto-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/blincyto-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/PASS/0000262863","type":"PASS","opinion":"2026-07-23","decision":"2026-09-18","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Post-Authorisation Safety Study"}, {"id":"EMA/VR/0000286935","type":"II","opinion":"2025-11-27","decision":"2026-03-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4, 4.8 of the SmPC in order to add a new warning on Haemophagocytic lymphohistiocytosis (HLH)/Immune effector-cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) following the evolving understanding of cytokine release syndrome and HLH/IEC-HS; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce editorial changes to the PI in line also with the latest QRD revision of the PI."}, {"id":"EMA/VR/0000263899","type":"II","opinion":"2025-06-19","decision":"2026-03-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to include information on a possible higher risk of seizures in patients with Down Syndrome who are receiving blinatumomab based on post marketing data and literature. The Package Leaflet is updated accordingly. The MAH also took the occasion to include some editorial changes in the PI."}, {"id":"II/0054","type":"II","opinion":"2025-03-13","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"To update sections 4.2, 4.4, 4.8 of the SmPC to include Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS); and to update section D of Annex II to remove educational materials for physicians, pharmacists, and to include ICANS within neurologic events in educational material for nurses and patient/caregivers and patient alert card following the outcome of PSUR procedure EMEA/H/C/PSUSA/00010460/202212. The Package Leaflet is updated accordingly. The RMP version 17.2 has also been submitted."}, {"id":"II/0056","type":"II","opinion":"2024-12-12","decision":"2025-01-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"II/0053/G","type":"II","opinion":"2024-02-22","decision":"2024-05-29","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"other","sections":["6.6"],"scope":"A grouped application consisting of: Type II (C.I.4): Update of sections 6.6 of the SmPC in order to add a statement that the administration of Blincyto for BSA of less than 0.4 m2 has not been established. In addition, the MAH took the opportunity to update the name of ATC pharmacological subgroup according to WHO ATC Index and to delete “intravenous catheter” from the important note statement regarding flushing and to introduce minor editorial changes to the PI. The Package Leaflet is updated accordingly."}, {"id":"II/0051","type":"II","opinion":"2023-10-26","decision":"2024-05-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update immunogenicity information to remove reference to antibody testing based on an analysis of all completed clinical studies and post-marketing data."}, {"id":"IB/0055","type":"IB","opinion":"2024-02-20","decision":"2024-05-29","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"R/0048","type":"R","opinion":"2023-01-26","decision":"2023-03-09","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0047/G","type":"II","opinion":"2022-09-01","decision":"2023-03-09","affects":["SmPC","Annex II"],"codes":["A.6","B.I.a.1.j","B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"The SmpC section 5.1 has been modified (Change in ATC Code from L01XC19 to L01FX07) The section A in Annex II (Manufacturers of the biological active substance and manufacturers responsible for batch release) has been updated as follows: Addition of the manufacturer “Amgen Inc One Amgen Center Drive Thousand Oaks, CA 91320 USA”"}, {"id":"II/0038","type":"II","opinion":"2021-05-20","decision":"2021-06-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include the use of blinatumomab as monotherapy for the treatment of paediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor ALL as part of the consolidation therapy; as a consequence, sections 4.1, 4.2, 4.8, 5.1, 5.2 of the SmPC are updated. In addition, section 6.6 of the SmPC is updated to improve readability of the instructions for preparation. The Package Leaflet is updated in accordance. Version 15 of the RMP has also been submitted."}, {"id":"IB/0041","type":"IB","opinion":"2021-03-31","decision":"2021-06-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00010460/202006","type":"PSUSA","opinion":"2021-01-28","decision":"2021-03-26","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - blinatumomab"}, {"id":"II/0030","type":"II","opinion":"2020-10-15","decision":"2020-12-22","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"To modify the approved therapeutic indication to include the treatment of Philadelphia chromosome positive CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL) in adult patients with relapsed or refractory ALL who have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC and the PL are updated accordingly. The updated RMP version 10.0 has also been submitted."}, {"id":"IB/0032","type":"IB","opinion":"2019-09-18","decision":"2019-10-21","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0011","type":"II","opinion":"2018-11-15","decision":"2019-01-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of adults with Philadelphia chromosome-negative CD19 positive B precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% for BLINCYTO monotherapy; as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and the RMP (version 9.1) are updated in accordance. In addition, the Marketing authorisation holder took the opportunity to update the contact details of the Portuguese and Irish local representatives in the Package Leaflet."}, {"id":"II/0018","type":"II","opinion":"2018-07-26","decision":"2018-08-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"IG/0946","type":"IG","opinion":"2018-06-04","decision":"2018-08-23","affects":["PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0009","type":"II","opinion":"2018-01-25","decision":"2018-06-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1","5.2","6.6"],"scope":"Update of sections 4.4, 4.8, 5.1 and 5.2 of the SmPC, Annex II and Package Leaflet based on the clinical study 103311 (TOWER): a Study of BITE antibody blinatumomab versus standard of care chemotherapy in adult subjects with relapsed/refractory b-precursor acute lymphoblastic leukaemia (ALL). The RMP (version 7.0) has been updated accordingly. In addition, the Marketing Authorisation Holder (MAH) took this opportunity to make editorials changes in section 6.6 of the SmPC. Finally, the CHMP recommends the granting of a marketing authorisation no longer subject to specific obligations."}, {"id":"PSUSA/00010460/201706","type":"PSUSA","opinion":"2018-01-25","decision":"2018-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - blinatumomab PSUSA/10460/201706."}, {"id":"IG/0853","type":"IG","opinion":"2017-11-10","decision":"2018-03-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IB/0016","type":"IB","opinion":"2017-07-28","decision":"2018-03-23","affects":["SmPC","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"PSUSA/00010460/201612","type":"PSUSA","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - blinatumomab"}, {"id":"II/0003","type":"II","opinion":"2016-09-15","decision":"2016-10-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a warning with regards to pancreatitis, and to section 4.4 to emphasise the mitigation of the risk of Cytokine Release Syndrome. In addition the MAH took the opportunity to make administrative changes section 4.2 and 5.1. The Package Leaflet is updated accordingly."}, {"id":"IB/0005","type":"IB","opinion":"2016-08-05","decision":"2016-10-21","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0002","type":"IB","opinion":"2016-04-28","decision":"2016-09-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"} ] }, "bortezomib__velcade": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/velcade-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"N/0103","type":"N","opinion":"2024-10-16","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0102","type":"II","opinion":"2024-05-16","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC in order to update information on pregnancy and preclinical clinical information following EMA/CHMP/SWP/74077/2020 rev. 1* dated on 30 March 2023. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and to update the list of local representatives in the Package Leaflet."}, {"id":"IA/0096","type":"IA","opinion":"2021-05-13","decision":"2022-06-07","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00000424/202004","type":"PSUSA","opinion":"2020-12-10","decision":"2021-02-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bortezomib"}, {"id":"II/0093","type":"II","opinion":"2020-02-13","decision":"2021-02-18","affects":["Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the RMP (finally agreed version 30.2) in line with the latest RMP template revision 2; as a consequence, Annex II of the PI is updated to reflect the removal of the additional risk minimisation activities (educational materials). In addition, the MAH took the opportunity to update the list of local representatives in the PL. Furthermore, the PI is being brought in line with the latest QRD template (version 10.1)."}, {"id":"PSUSA/00000424/201804","type":"PSUSA","opinion":"2018-12-13","decision":"2019-02-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bortezomib"}, {"id":"II/0090","type":"II","opinion":"2018-09-20","decision":"2019-02-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0083","type":"IB","opinion":"2017-02-21","decision":"2018-02-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0079","type":"II","opinion":"2015-12-17","decision":"2016-01-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to include information from paediatric study AALL07P1. The MAH also took the opportunity to correct some minor editorial mistakes in the SmPC."}, {"id":"PSUSA/00000424/201504","type":"PSUSA","opinion":"2015-11-19","decision":"2016-01-14","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bortezomib"}, {"id":"II/0075","type":"II","opinion":"2015-04-23","decision":"2016-01-14","affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 Pharmacodynamic properties of the SmPC following the submission of long term follow-up and survival analysis from Study Doxil-MMY-3001 - evaluation of efficacy and safety for Doxil/Caelyx in combination with VELCADE compared to the VELCADE monotherapy for treatment of subjects with multiple myeloma whose disease had progressed after an initial response to at least 1 line of prior therapy or was refractory to initial treatment. The MAH had committed to provide this information during VELCADE variation procedure EMEA/H/C/539/II/63 and CAELYX variation procedure EMEA/H/C/089/II/45."}, {"id":"N/0071","type":"N","opinion":"2014-03-18","decision":"2015-01-30","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0072","type":"II","opinion":"2014-12-18","decision":"2015-01-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for the use of VELCADE in combination with rituximab, cyclophosphamide, doxorubicin and prednisone for the treatment of adult patients with previously untreated mantle cell lymphoma. Consequently, the MAH proposed updates of sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC and the Package Leaflet."}, {"id":"R/0066","type":"R","opinion":"2013-11-21","decision":"2014-01-10","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0063/G","type":"II","opinion":"2013-11-21","decision":"2013-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extensions of indication for Velcade in combination with pegylated liposomal doxorubicin or in combination with dexamethasone in patients with relapsed and /or progressive multiple myeloma who have received at least 1 prior therapy. Consequently, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC have been updated. The package leaflet has been updated accordingly. Editorial changes were also made to the product information. Annex II has also been corrected to add the key elements with regards to the induction transplant regimens to minimise the risk of medication errors. The list of local representatives in the package leaflet has also been updated."}, {"id":"II/0062","type":"II","opinion":"2013-06-27","decision":"2013-07-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to add the results of a study on Velcade retreatment in patients with relapsed multiple myeloma. The package leaflet was updated accordingly. In addition, the MAH took the opportunity to make editorial changes and to update the list of local representatives in the Package Leaflet, including the contact details of the local representatives in Croatia. Furthermore, the product information was updated in line with the latest QRD template version 9."}, {"id":"II/0061","type":"II","opinion":"2013-03-21","decision":"2013-07-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to add a warning on Progressive Multifocal Leukoencephalopathy. The Package Leaflet is updated accordingly. The MAH also took the opportunity to make minor editorial changes and update the list of local representatives in the package leaflet. Furthermore, Annex II has been updated in line with the latest QRD template version 8.3."}, {"id":"II/0059","type":"II","opinion":"2013-06-27","decision":"2013-07-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.6","4.8","5.1"],"scope":"Extension of the indication of Velcade in combination with dexamethasone, or with dexamethasone and thalidomide, for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high dose chemotherapy with haematopoietic stem cell transplantation. Consequently, sections 4.1, 4.2, 4.3, 4.4, 4.6, 4.8 and 5.1 of the Summary of Product Characteristics and the package leaflet have been updated. The MAH also took the opportunity to make editorial changes to the product information."}, {"id":"X/0047","type":"X","opinion":"2012-06-21","decision":"2012-09-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application for a new route of administration for subcutaneous use of Velcade 3.5 mg powder for solution for injection."}, {"id":"II/0054","type":"II","opinion":"2012-01-19","decision":"2012-03-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to the adverse reactions “optic neuropathy” and “different degrees of visual impairment (up to blindness)” with a rare frequency. The Package Leaflet has been updated accordingly. In addition, editorial changes have also been made to the SmPC and Package Leaflet."}, {"id":"S/0052","type":"S","opinion":"2011-12-15","decision":"2012-03-19","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"“7th Annual Re-assessment”"}, {"id":"II/0053","type":"II","opinion":"2011-12-15","decision":"2012-03-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with final survival data from Study MMY-3002. The MAH also took the opportunity to make minor editorial changes to the SmPC."}, {"id":"II/0050","type":"II","opinion":"2011-07-21","decision":"2011-08-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the Summary of Product Characteristics (SmPC) with regard to the interaction of Velcade with CYP3A4 inducers further to the results of a drug-drug interaction study of Velcade and rifampicin and dexamethasone. The Package leaflet has been updated accordingly. The MAH also took the opportunity to update the list of local representatives in the package leaflet."}, {"id":"II/0046","type":"II","opinion":"2011-05-19","decision":"2011-06-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.3","4.4","5.2"],"scope":"Update of sections 4.2, 4.3, 4.4 and 5.2 of the SmPC and the Package Leaflet (PL), in particular to remove the contraindication of Velcade in patients with severe hepatic impairment, further to the results of a study of Velcade in subjects with advanced malignancies and varying degrees of hepatic dysfunction that was conducted in order to fulfil a specific obligation (SO2 011.1). The MAH also took the opportunity to make editorial changes to the product information and update the list of local representatives in the PL."}, {"id":"S/0045","type":"S","opinion":"2010-09-23","decision":"2010-12-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0041","type":"II","opinion":"2010-05-20","decision":"2010-07-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Further to the results of a phase 1/2 study conducted as a specific obligation (SOB 015) to determine the safety and efficacy of VELCADE in patients with previously treated light-chain amyloidosis, the marketing authorisation holder of VELCADE applied to update section 4.4 of the Summary of Product Characteristics (SmPC) to remove the warning on amyloidosis and to include the results of this study in section 5.1 of the SmPC. The package leaflet is updated accordingly."}, {"id":"II/0040","type":"II","opinion":"2010-04-22","decision":"2010-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Summary of Product Characteristics with updated survival data from Study MMY-3002. The MAH also took the opportunity to include a correction and update the list of local representatives in the Package Leaflet."}, {"id":"IB/0042","type":"IB","opinion":"2010-05-19","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of sections 2, 4.2, 4.6, 5.1, 6.5 and 10 of the Summary of Product Characteristics, Annex II and the Package Leaflet, to align with the new QRD template version 7.3."}, {"id":"II/0039","type":"II","opinion":"2010-03-18","decision":"2010-04-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Further to the conduct of cumulative reviews requested by the CHMP in the assessment of the 10th PSUR and 5th annual re-assessment, the MAH proposed to update section 4.4 of the Summary of Product Characteristics (SmPC) to add a warning on Reversible Posterior Leukoencephalopathy Syndrome (RPLS) and to add the adverse reactions in section 4.8 RPLS, acute febrile neutrophilic dermatosis and leukocytoclastic vasculitis. The Package Leaflet has been updated accordingly."}, {"id":"S/0035","type":"S","opinion":"2009-09-24","decision":"2009-11-30","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0036","type":"II","opinion":"2009-09-24","decision":"2009-10-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"There is a body of preclinical studies and clinical observations on the effect of Velcade on bone. As a consequence, the following paragraph was added to section 5.1 of the Summary of Product Characteristics (SPC): \"Data from in vitro, ex-vivo, and animal models with Bortezomib suggest that it increases osteoblast differentiation and activity and inhibits osteoclast function. These effects have been observed in patients with multiple myeloma affected by an advanced osteolytic disease and treated with Bortezomib.\""}, {"id":"II/0034","type":"II","opinion":"2009-04-23","decision":"2009-05-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SPC to include a recommendation regarding the use of antiviral prophylaxis therapy for herpes zoster virus reactivation in patients treated with Velcade and to add Steven Johnson Syndrome and Toxic Epidermal Necrolysis as adverse reactions from post-marketing reports with a frequency \"not known\", further to safety related revisions to the Company Core Data Sheet (CCDS). The Package Leaflet is updated accordingly. The MAH also took the opportunity to make some editorial changes to the SPC and to update the contact details of Bulgaria and Germany in the list of local representatives in the Package Leaflet."}, {"id":"R/0032","type":"R","opinion":"2009-01-22","decision":"2009-03-31","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0031","type":"N","opinion":"2008-11-14","decision":null,"affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"S/0030","type":"S","opinion":"2008-09-25","decision":"2008-11-04","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0028","type":"II","opinion":"2008-07-24","decision":"2008-08-29","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of the indication for Velcade in combination with melphalan and prednisone for the treatment of patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with bone marrow transplant. Subsequently, changes to sections 4.2, 4.4, 4.5, 4.8 and 5.1 of the SPC have been made. The Package Leaflet has been updated accordingly. Annex II has been updated to include the agreed version of the EU RMP (version 2.0)."}, {"id":"II/0029","type":"II","opinion":"2008-06-26","decision":"2008-07-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.2"],"scope":"Update of SPC sections 4.2, 4.4 & 5.2 based on available data from a renal impairment study, a specific obligation to the original marketing authorisation. Further, as requested with the CHMP assessment of PSUR 7, SPC section 4.8 was updated with the ADR\"septic shock\" under the SOC Infections and infestations in the Post Marketing Experience paragraph. In addition, the MAH took the opportunity to update the list of local representatives in the package leaflet."}, {"id":"II/0027","type":"II","opinion":"2008-03-19","decision":"2008-04-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Addition of a contraindication in Acute diffuse infiltrative pulmonary and pericardial disease."}, {"id":"II/0026","type":"II","opinion":"2008-03-19","decision":"2008-04-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"New presentation New presentation(s)"}, {"id":"S/0022","type":"S","opinion":"2007-11-15","decision":"2008-01-10","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0025","type":"II","opinion":"2007-11-15","decision":"2007-12-14","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"This variation concerns an update of section 4.5 of the SPC with the results of two drug interaction studies with a CYP3A4 inhibitor and a CYP2C19 inhibitor, respectively, and was submitted by the MAH upon request by the CHMP following the assessment of Specific obligations 012 and 013. The SPC has been updated with the following information: A drug-drug interaction study based on data from 12 patients, assessing the effect of ketoconazole, a potent CYP3A-inhibitor, showed a bortezomib AUC mean increase of 35% (CI90% [1.032 to 1.772]). Therefore patients should be closely monitored when given bortezomib in combination with potent CYP3A4-inhibitors (e.g. ketoconazole, ritonavir)."}, {"id":"II/0019","type":"II","opinion":"2007-05-24","decision":"2007-07-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"The MAH applied for a type II variation to update sections 4.2 and 4.4 of the SPC with more information regarding 'motor neuropathy'. The CHMP considered that in order to try to identify patients at risk of neuropathy, a diagnostic approach that would include a neurological assessment seems to be necessary, especially in those patients experiencing new or worsening peripheral neuropathy. Further, section 4.4 of the SPC has been updated with information regarding a potential interaction with cytarabine."}, {"id":"IB/0020","type":"IB","opinion":"2007-03-28","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"S/0016","type":"S","opinion":"2006-10-18","decision":"2007-01-03","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0015","type":"II","opinion":"2006-06-28","decision":"2006-07-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH applied for a type II variation, upon request by CHMP, to include further pulmonary safety information in section 4.4 of the Summary of Product Characteristics (SPC) and to update section 4.8 of the SPC with the following ADRs: \"pneumonitis\", \"interstitial pneumonia\", \"Acute Respiratory Distress Syndrome (ARDS)\", \"encephalopathy\", \"cardiac tamponade\", \"ischemic colitis\" and \"liver failure\". In addition, the MAH took the opportunity to update the addresses of the local representatives in the Package Leaflet."}, {"id":"S/0011","type":"S","opinion":"2005-10-13","decision":"2006-01-19","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0014","type":"II","opinion":"2005-09-15","decision":"2005-10-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH applied for an update of sections 4.4 and 4.8 of the SPC to include additional information regarding hepatic and cardiac adverse events resulting from ongoing safety monitoring. A warning on \"Hepatic Reactions\" was added: \"Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic reactions include asymptomatic increases in liver enzymes, hyperbilirubinaemia, and hepatitis."}, {"id":"II/0008","type":"II","opinion":"2005-06-23","decision":"2005-07-27","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.9","5.3"],"scope":"The MAH applied for an update of SPC section 4.9 \"Overdosage\" to include additional information following the assessment of the first PSUR and further to new non-clinical data on an investigational model (in vitro and in vivo), which are relevant to the clinical overdose situation. In line with the current Guideline on SPCs, references to the animal models have been included in SPC section 5.3. Two cardiovascular safety pharmacology studies in monkeys and dogs show that IV doses approximately two to three times the recommended clinical dose on a mg/m2 basis are associated with increases in heart rate, decreases in contractility, hypotension and death."}, {"id":"II/0007","type":"II","opinion":"2005-06-23","decision":"2005-07-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"The MAH applied for an update of SPC section 4.8 \"Undesirable effects\" to include additional information regarding adverse reactions (cardiac tamponade, ischemic colitis, encephalopathy) further to the assessment of the first PSUR. In addition, acute pancreatitis and a wording on ECG investigations were included in section 4.8. The MAH also took this opportunity to re-organise the information in section 4.8 in accordance with the SPC guideline. In addition, the list of local representatives in the Patient Leaflet was updated."}, {"id":"II/0005","type":"II","opinion":"2005-03-16","decision":"2005-04-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of the indication to allow patients who have received at least one prior therapy (instead of at least two) to be treated. As a result, sections 4.1, 4.2, 4.4, 4.8 and 5.1 in the SPC have been amended and corresponding changes in the PL have been made."}, {"id":"IB/0006","type":"IB","opinion":"2004-11-08","decision":null,"affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - after dilution/reconstitution"}, {"id":"T/0004","type":"T","opinion":"2004-07-30","decision":"2004-09-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IA/0001","type":"IA","opinion":"2004-05-10","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in BR/QC testing - repl./add. manuf. responsible for BR - incl. BC/testing"} ] }, "bosutinib__bosulif": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/bosulif-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/bosulif-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000319527","type":"IAIN","opinion":"2026-01-11","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Cutaneous vasculitis following the outcome of EPITT 20184."}, {"id":"EMA/VR/0000302255","type":"IAIN","opinion":"2025-09-30","decision":null,"affects":["PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"X/0058/G","type":"X","opinion":"2025-03-27","decision":"2025-06-02","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0060","type":"II","opinion":"2024-11-21","decision":"2025-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on cardiovascular toxicity and to add cardiac failure and cardiac ischaemic events to the list of adverse drug reactions (ADRs) with frequency common, based on an updated safety review. The Package Leaflet is updated accordingly."}, {"id":"IAIN/0056","type":"IAIN","opinion":"2023-05-16","decision":"2024-05-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0050/G","type":"II","opinion":"2022-01-27","decision":"2022-04-07","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"(Type II) C.I.4 - Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC in order to reflect results from studies B1871039 (specific obligation) and B1871040 (post-authorisation safety study); The Package Leaflet is updated accordingly. An updated RMP (version 6.0) has also been submitted. Update of Annex II to remove the specific obligation and conversion of the conditional marketing authorisation into a marketing authorisation not subject to specific obligations. Section 5.1 of the SmPC and Section 6 of the PL are updated accordingly to remove the reference to the conditional marketing authorisation."}, {"id":"II/0048","type":"II","opinion":"2021-07-22","decision":"2022-03-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC in order to update safety and efficacy information based on final results from study B18711053 (a recommendation of EMEA/H/C002373/II/25/G). This is an interventional safety and efficacy study covering submission of the long-term experience results secondary endpoints (duration of MMR and CCyR, EFS and OS). The Safety Data pool is also updated with results of interventional studies, B18711048 (final CSR submitted in variation II/41) and ongoing studies B18711039 and B18711040 (listed as category 3 studies in the RMP); the Package Leaflet is updated accordingly."}, {"id":"N/0046","type":"N","opinion":"2020-11-27","decision":"2021-02-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00010073/202003","type":"PSUSA","opinion":"2020-10-15","decision":"2020-12-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bosutinib"}, {"id":"II/0043","type":"II","opinion":"2020-09-03","decision":"2020-12-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.3"],"scope":"Update of section 5.3, of the SmPC in order to update non-clinical information following the final results from the six-month transgenic rasH2 mouse carcinogenicity study, listed as a category 3 in the current approved RMP version 4.5. ; The RMP version 5.0 has also been submitted. The MAH took the opportunity to implement changes resulting from the revision of the SmPC guideline on excipients, applied in the SmPC section 4.4 and in the Package Leaflet section 2."}, {"id":"II/0041","type":"II","opinion":"2020-07-23","decision":"2020-12-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.2"],"scope":"Update of sections 4.4 and 5.2 of the SmPC with additional safety and PK data from the recently completed Phase 2 study (B1871048) following a commitment within variation EMEA/H/C/002373/II/0036 and a pooled safety data analysis performed to assess the clinical impact of reduced clearance in Asian population. The MAH takes also the opportunity to make editorial changes on the Package Leaflet"}, {"id":"N/0040","type":"N","opinion":"2019-11-13","decision":"2020-02-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0037","type":"II","opinion":"2019-05-16","decision":"2020-02-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC based on final results from An Oral (Gavage) Study of the Effects of PF-05208763 on Pre- and Postnatal Development, Including Maternal Function in Rats listed as a category 3 study in the RMP. The Package leaflet is updated accordingly. The updated RMP version 4.5 has also been submitted."}, {"id":"R/0035","type":"R","opinion":"2018-12-13","decision":"2019-02-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0030","type":"II","opinion":"2018-10-18","decision":"2019-02-18","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of an updated RMP (finally agreed version 4.4) in line with changes requested by the CHMP following variation II/25/G in fulfilment of REC 014; in addition, the MAH took the opportunity to extend the due date of the Specific Obligation (SOB) study of the conditional marketing authorisation. Annex II has been updated accordingly."}, {"id":"T/0032","type":"T","opinion":"2018-07-11","decision":"2018-08-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"X/0026","type":"X","opinion":"2018-03-22","decision":"2018-05-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to add a new strength of 400 mg film-coated tablets"}, {"id":"II/0028","type":"II","opinion":"2018-03-15","decision":"2018-05-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC following further analyses of the pharmacokinetic (PK) data from Study B1871044 that has been already submitted to the EMA previously."}, {"id":"II/0025/G","type":"II","opinion":"2018-02-22","decision":"2018-04-23","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of Indication to include treatment of adult patients with newly diagnosed Philadelphia Chromosome positive (Ph+) Chronic Phase (CP) Chronic Myelogenous Leukaemia (CML) for Bosulif based on study AV001. In addition, the MAH updated the SmPC with safety and efficacy information from studies B1871006 and B1871008. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated accordingly. Moreover, the updated RMP version 4.1 was agreed during the procedure. Furthermore, the Annex IIIA is brought in line with the latest QRD template version 10."}, {"id":"R/0027","type":"R","opinion":"2017-12-14","decision":"2018-02-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"R/0023","type":"R","opinion":"2017-01-26","decision":"2017-03-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010073/201603","type":"PSUSA","opinion":"2016-10-13","decision":"2016-12-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bosutinib"}, {"id":"IAIN/0021","type":"IAIN","opinion":"2016-05-11","decision":"2016-12-08","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0018","type":"II","opinion":"2015-10-22","decision":"2016-01-07","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to update the Pharmacokinetic properties information after analysis of final study report for study B1871044 (open label, randomised, 2-period crossover study to evaluate absolute bioavailability of bosutinib in healthy subjects) in fulfilment of MEA 005.2; in addition, the Marketing authorisation holder (MAH) took the opportunity to correct minor errors in the Package Leaflet, to combine the SmPC of the 100 mg and 500 mg presentations and to bring the PI in line with the latest QRD template version 9.1."}, {"id":"PSUSA/00010073/201503","type":"PSUSA","opinion":"2015-09-24","decision":"2015-11-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - bosutinib"}, {"id":"N/0015","type":"N","opinion":"2015-06-24","decision":"2015-11-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0014/G","type":"II","opinion":"2015-07-23","decision":"2015-11-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to include further information related to concomitant use of Bosulif with CYP3A inhibitors based on the results of Study B1871041, and in order to reflect the results of Study B1871043 submitted to fulfil MEA 003.2 and undertaken to investigate the drug interaction potential with regard to bosutinib being a P-gp inhibitor. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC and Package Leaflet. A revised RMP version 3.1 was agreed during the procedure."}, {"id":"IB/0013","type":"IB","opinion":"2014-12-23","decision":"2015-11-23","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0008","type":"II","opinion":"2014-10-23","decision":"2015-02-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0001","type":"II","opinion":"2014-05-22","decision":"2014-06-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC further to the results of study B1871020 in patients with renal impairment conducted as a post-authorisation measure (MEA 006) and population pharmacokinetic modelling. The Package Leaflet is updated accordingly."}, {"id":"IB/0006","type":"IB","opinion":"2014-05-22","decision":"2014-06-23","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"R/0002","type":"R","opinion":"2013-11-21","decision":"2014-02-20","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."} ] }, "brentuximab-vedotin__adcetris": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/adcetris-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/adcetris-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000323310","type":"IB","opinion":"2026-02-18","decision":null,"affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"To update SmPC section 4.2 to include \"4\" to correctly reflect \"other CTCAE Grade 4 toxicities” (rather than the current texts of “other CTCAE grade toxicities) in line with the data available."}, {"id":"II/0113","type":"II","opinion":"2025-01-16","decision":"2025-06-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update clinical information based on final results from ECHELON-1 final OS analysis data (C25003 CSR addendum 3). This is a randomized, open-label, phase 3 trial of A+AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. In addition, the MAH took the opportunity to update the PI according to the Excipients Guideline and to introduce minor formatting changes to the PI."}, {"id":"II/0111","type":"II","opinion":"2025-04-25","decision":"2025-06-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication for ADCETRIS to include treatment for adult patients with previously untreated CD30+ Stage IIB with risk factors, Stage III or Stage IV HL in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD), based on final results from phase 3 study HD21 (NCT02661503). This study is titled Treatment Optimization Trial in the First-Line Treatment of Advanced-Stage Hodgkin Lymphoma; Comparison of 4-6 Cycles of Escalated BEACOPP With 4-6 Cycles of BrECADD. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 20.0 of the RMP has also been submitted."}, {"id":"II/0107","type":"II","opinion":"2023-09-14","decision":"2023-10-12","affects":["SmPC"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1"],"scope":"Extension of indication to include treatment of adult patients with previously untreated CD30+ Stage III Hodgkin lymphoma (HL), in combination with doxorubicin, vinblastine and dacarbazine (AVD), for ADCETRIS, based on the second interim analysis of OS data from ECHELON-1 study (C25003); this is a randomized, open-label, phase 3 trial of A+AVD versus ABVD as frontline therapy in patients with advanced classical HL. As a consequence, sections 4.1 and 5 of the SmPC are updated. Version 18.0 of the RMP has also been submitted. The variation leads to amendments to the Summary of Product Characteristics."}, {"id":"II/0103","type":"II","opinion":"2022-11-17","decision":"2023-10-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to reflect new safety and efficacy information based on long-term data from the second interim analysis of OS (103 events) from study ECHELON-1, undertaken in previously untreated CD30+ Stage IV HL. In addition, following the completion of all specific obligations and considering the recent switch from a conditional to a full MA (variation II-99), the MAH takes the opportunity to propose the removal of the black triangle (regarding additional monitoring) from the SmPC and the Package Leaflet."}, {"id":"II/0099","type":"II","opinion":"2022-03-24","decision":"2022-05-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC, based on final results from study C25006, a multi-centre open-label, phase 4 study of 50 patients with r/r sALCL undertaken to further evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult patients who had previously received at least 1 multiagent chemotherapy regimen. This study was listed as an interventional category 2 PASS in the RMP (SOB 010)."}, {"id":"IA/0101/G","type":"IA","opinion":"2022-03-29","decision":"2022-04-13","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0093","type":"II","opinion":"2021-11-11","decision":"2021-12-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2","6.6"],"scope":"Update of sections 4.2, 4.8, 5.1, 5.2, and 6.6 of the SmPC based on the final results from study C25004, an open-label study in order to assess the safety and tolerability, of brentuximab vedotin when combined with multiagent chemotherapy regimen for first-line treatment of advanced-stage Hodgkin lymphoma in paediatric patients, in order to complete the PIP (P/0013/2021) and in order to fulfil Article 46 of Regulation EC No 1901/2006. The RMP version 16 has also been submitted."}, {"id":"PSUSA/00010039/202102","type":"PSUSA","opinion":"2021-10-14","decision":"2021-12-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brentuximab vedotin"}, {"id":"N/0092","type":"N","opinion":"2021-09-07","decision":"2021-12-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0089","type":"II","opinion":"2021-09-16","decision":"2021-12-09","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Submission of long-term follow-up data for clinical trial Echelon-2 (SGN035-014): A randomized, double-blind, placebo-controlled, phase 3 study of brentuximab vedotin and CHP (A+CHP) versus CHOP in the frontline treatment of patients with CD30-positive mature T-cell lymphoma. The study is submitted to fulfil the post-approval-measure MEA 015.1. Section 5.1 of the SmPC has been updated to reflect this follow-up."}, {"id":"IAIN/0094","type":"IAIN","opinion":"2021-07-27","decision":"2021-12-09","affects":["Annex II"],"codes":["B.I.e.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - Requires no further supportive data"}, {"id":"II/0086","type":"II","opinion":"2021-04-22","decision":"2021-09-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the SmPC section 5.1 following the submission of the CSR addendum which includes long-term follow up or final OS results for the AETHERA study “A phase 3, randomised, double-blind, placebo-controlled, multicentre, clinical trial in patients with Hodgkin Lymphoma (HL) at risk of relapse or progression following ASCT”"}, {"id":"II/0085","type":"II","opinion":"2021-04-22","decision":"2021-09-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the SmPC section 5.1 following the 5 -year long-term follow up for the C25007 study in HL. Editorial updates have been also implemented in the PI. In addition, the MAH took the opportunity to update the list of local representatives for The Netherlands and United Kingdom (Northern Ireland) in the package leaflet."}, {"id":"PSUSA/00010039/202002","type":"PSUSA","opinion":"2020-10-15","decision":"2020-12-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brentuximab vedotin"}, {"id":"IB/0081","type":"IB","opinion":"2020-09-25","decision":"2020-12-14","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0083","type":"IAIN","opinion":"2020-09-02","decision":"2020-12-14","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"SW/0074","type":"SW","opinion":"2020-05-28","decision":"2020-07-23","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Post Authorisation Safety Study results - EMEA/H/C/PSR/S/0022"}, {"id":"II/0070","type":"II","opinion":"2020-03-26","decision":"2020-05-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of indication to include in combination with cyclophosphamide, doxorubicin, and prednisone treatment of adults with previously untreated CD30+ sALCL for Adcetris; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC are being updated to reflect the indication. The Package Leaflet (PL) is updated in accordance. Version 15.2 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI is brought in line with the latest QRD template version 10.1."}, {"id":"II/0055","type":"II","opinion":"2018-12-13","decision":"2019-02-06","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","6.6"],"scope":"Extension of the existing Hodgkin lymphoma (HL) indication to include the frontline treatment of adult patients with CD30+ Stage IV HL in combination with doxorubicin, vinblastine and dacarbazine (AVD), based on data from ECHELON-1 (C25003), a phase 3 multi-centre, randomised, open-label study comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin, doxorubicin, vinblastine and dacarbazine versus the mPFS obtained with doxorubicin, bleomycin, vinblastine and dacarbazine. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"N/0060","type":"N","opinion":"2018-07-25","decision":"2018-09-10","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0049","type":"II","opinion":"2018-01-11","decision":"2018-09-10","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC with data from study C25002; a phase 1/2 study of brentuximab vedotin (SGN-35) in paediatric patients with relapsed or refractory systemic anaplastic large cell lymphoma or Hodgkin’s lymphoma (listed in the agreed PIP covering the conditions of Hodgkin lymphoma and anaplastic large cell lymphoma for ADCETRIS (EMEA-000980-PIP01-10-M04)). An updated RMP version 12.3 was provided as part of the application."}, {"id":"II/0048","type":"II","opinion":"2017-11-09","decision":"2017-12-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the new indication “ADCETRIS is indicated for the treatment of adult patients with CD30+ cutaneous T-cell lymphoma (CTCL) who require systemic therapy”, based on data from study C25001 (the ‘ALCANZA’ study): “A Phase 3 Trial of brentuximab vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma”. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. An updated RMP (version 10.1) has also been submitted."}, {"id":"R/0051","type":"R","opinion":"2017-09-14","decision":"2017-11-10","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0045","type":"II","opinion":"2017-06-22","decision":"2017-11-10","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to add 5-year follow-up overall survival (OS) data from patients included in study SG035-0004, a phase 2 open-label study of brentuximab vedotin in the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL), in accordance with the specific obligation SOB 028. Annex II of the product information and the RMP (version 9.0) are updated accordingly."}, {"id":"II/0043","type":"II","opinion":"2017-07-20","decision":"2017-11-10","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to reflect the final study results from study C25007: a single-arm study of brentuximab vedotin in patients with relapsed or refractory hodgkin lymphoma who are not suitable for stem cell transplantation or multiagent chemotherapy. The submission of the clinical study report fulfils SOB 011 of the conditional marketing authorisation for Adcetris Annex II is updated accordingly."}, {"id":"IB/0044","type":"IB","opinion":"2017-01-14","decision":"2017-11-10","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0052","type":"IAIN","opinion":"2017-07-19","decision":"2017-11-10","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0040","type":"IAIN","opinion":"2016-11-14","decision":"2017-11-10","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"IB/0038","type":"IB","opinion":"2016-06-28","decision":"2016-10-21","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0033","type":"II","opinion":"2016-04-28","decision":"2016-06-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to reflect clinical pharmacology data from study C25005. The provision of the final CSR for study C25005 addresses the post-authorisation measure MEA 013."}, {"id":"II/0032","type":"II","opinion":"2016-04-01","decision":"2016-06-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of SmPC section 5.1 to include 5-year observed survival data from the SGN035-0003 study in patients with relapsed or refractory Hodgkin lymphoma. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet."}, {"id":"II/0030/G","type":"II","opinion":"2016-04-28","decision":"2016-06-24","affects":["SmPC","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC in order to add a warning on hepatotoxicity, further to the outcome of the PSUR assessment (PSUSA 010039-201502). The Package Leaflet and RMP (version 6.2) are updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet. Update of section 4.4 of the SmPC in order to add a warning on gastrointestinal complications. The Package Leaflet and RMP are updated accordingly. Update of section 4.4 of the SmPC in order to update a warning on pulmonary toxicity, providing examples of pulmonary toxicity diagnoses. The Package Leaflet and RMP are updated accordingly."}, {"id":"II/0025","type":"II","opinion":"2016-05-26","decision":"2016-06-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include the treatment of adult patients with Hodgkin Lymphona (HL) at increased risk of relapse or progression following autologous stem cell transplantation (ASCT). As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet and the RMP (v.6.3) are updated in accordance. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"IB/0034/G","type":"IB","opinion":"2016-03-15","decision":"2016-06-24","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0029/G","type":"IAIN","opinion":"2015-12-21","decision":"2016-06-24","affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0028","type":"II","opinion":"2015-10-22","decision":"2015-11-19","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the 50 mg powder for concentrate for solution SmPC based on the results of study SGN35-006 Part A, to allow retreatment of adult patients who have responded to previous treatment with brentuximab vedotin under the existing indications. In addition, the MAH took the opportunity to bring the SmPC and Annex II in line with the latest QRD template version 9.1. A revised RMP version 5.3 was agreed during the procedure. The requested variation proposed amendments to the Summary of Product Characteristics (SmPC), Annex II and to the Risk Management Plan (RMP)."}, {"id":"II/0020","type":"II","opinion":"2014-11-20","decision":"2015-07-03","affects":["Annex II"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"To add manufacturer of the Active Substance (AS)"}, {"id":"II/0018","type":"II","opinion":"2014-07-24","decision":"2015-07-03","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0024","type":"IAIN","opinion":"2015-03-02","decision":"2015-07-03","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0012","type":"II","opinion":"2014-06-26","decision":"2014-08-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to present updated advice to physicians on treatment with Adcetris of patients with hepatic or renal impairment based on data from study SGN-35-008b. The Package Leaflet is updated accordingly."}, {"id":"II/0011","type":"II","opinion":"2014-01-23","decision":"2014-08-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect the updated overall survival (OS) and Progression Free survival (PFS) analyses from both pivotal studies SG035-0003 and SG035-0004 in Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) patients respectively. Annex II has been updated accordingly to remove part of the SOB-001. In addition, the MAH took the opportunity to add the list of local representatives in the Package Leaflet."}, {"id":"II/0010","type":"II","opinion":"2014-03-20","decision":"2014-08-22","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to include the common adverse drug reaction ‘Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased’ under Hepatobiliary disorders following a PRAC recommendation and ‘sepsis/septic shock’ to ensure alignment with the RMP, where ‘infections including bacteraemia, sepsis and septic shock’ is already an important identified risk. The Package Leaflet is updated accordingly."}, {"id":"II/0009","type":"II","opinion":"2014-01-23","decision":"2014-08-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC to extend the recommendation of contraception for women of childbearing potential during treatment with brentuximab vedotin from 30 days to 6 months after treatment, further to a review of the protocols of studies with brentuximab vedotin and of existing recommendations for other antineoplastic chemotherapies with a similar mechanism of action. The Package Leaflet is updated accordingly."}, {"id":"II/0008","type":"II","opinion":"2013-11-21","decision":"2014-08-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a warning regarding the risk of pulmonary toxicity further to a PRAC recommendation following the review of a signal identified in Eudravigilance. The Package Leaflet is updated accordingly. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"II/0007","type":"II","opinion":"2013-11-21","decision":"2014-08-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information related to the new important potential risk of acute pancreatitis. The Package Leaflet is updated accordingly. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"R/0005","type":"R","opinion":"2013-06-27","decision":"2013-08-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0002","type":"II","opinion":"2013-02-21","decision":"2013-08-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to clarify the sources of the safety data (adverse drug reactions) presented, and to add the adverse reactions of progressive multifocal leukoencephalopathy (PML), anaphylactic reactions and febrile neutropenia that occurred outside of the phase 2 pivotal studies in the tabulated list of adverse reactions. The Package Leaflet has been updated accordingly. Furthermore, the MAH has taken this opportunity to bring the PI in line with the latest QRD template version 8.3 and to implement minor editorial changes."}, {"id":"IAIN/0004","type":"IAIN","opinion":"2013-05-08","decision":"2013-08-26","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer responsible for batch release"} ] }, "brexucabtagene-autoleucel__tecartus": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tecartus-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tecartus-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00010903/202507","type":"PSUSA","opinion":"2026-02-26","decision":"2026-05-04","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brexucabtagene autoleucel"}, {"id":"EMA/VR/0000309793","type":"II","opinion":"2026-02-26","decision":"2026-05-04","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.c"],"outcome":"accepted","kind":"other","sections":["6.4"],"scope":"The SmPC section 6.4 has been updated as follows: Yescarta/Tecartus must be stored at ≤ -120 ̊C and must remain frozen until the patient is ready for treatment to ensure viable live autologous cells are available for patient administration. The Labelling and PL have been updated accordingly."}, {"id":"EMA/VR/0000285857","type":"II","opinion":"2025-11-13","decision":"2026-05-04","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a reference statement to current institutional / national guidelines for the monitoring and management of CRS, neurologic events and ICANS. In addition, the MAH took the opportunity to introduce clarification and administrative updates across the PI, including Annex II."}, {"id":"EMA/VR/0000308229","type":"II","opinion":"2026-04-23","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.7","6.4"],"scope":"Update of sections 4.2, 4.4, 4.5. 4.7 and 6.4 of the SmPC in order to modify the pre- and post-infusion monitoring recommendations and requirements related to the risk of CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome) based on data from clinical trials, post-marketing experience and literature. The Package Leaflet is updated accordingly. The RMP version 8.0 for Tecartus and RMP version 13.0 for Yescarta have also been submitted. In addition, Annex II has been updated accordingly."}, {"id":"PSUSA/00010903/202501","type":"PSUSA","opinion":"2025-09-18","decision":"2025-11-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brexucabtagene autoleucel"}, {"id":"EMA/VR/0000257524","type":"II","opinion":"2025-05-22","decision":"2025-11-17","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the 57-month follow-up results from study ZUMA-3 (KTE-C19-103) listed as a Specific Obligation in the Annex II of the Product Information. This is a phase 1/2 open-label study evaluating the safety and efficacy of brexucabtagene autoleucel in adult participants with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL). The Annex II is updated accordingly."}, {"id":"EMA/VR/0000255932","type":"II","opinion":"2025-07-24","decision":"2025-11-17","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.c"],"outcome":"accepted","kind":"other","sections":["6.4"],"scope":"The SmPC section 6.4 has been updated as follows: Yescarta/Tecartus may be stored a single time at - 80 °C (± 10 °C), for up to 90 days. After storage at -80 °C (± 10 °C), the product must be used within the 90-day period or the labelled expiration date, whichever comes first. After these dates, the product must not be used and must be discarded. The Labelling and Package Leaflet have been updated accordingly."}, {"id":"WS/2632","type":"WS","opinion":"2024-04-25","decision":"2025-02-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to update the safety monitoring timelines based on data from clinical studies, postmarketing studies, and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to other sections of the SmPC to align the language across both products."}, {"id":"R/0047","type":"R","opinion":"2024-12-12","decision":"2025-02-26","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IG/1781","type":"IG","opinion":"2024-08-14","decision":"2025-02-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0044","type":"IB","opinion":"2024-05-14","decision":"2025-02-26","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00010903/202307","type":"PSUSA","opinion":"2024-02-22","decision":"2024-04-19","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brexucabtagene autoleucel"}, {"id":"R/0034","type":"R","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010903/202301","type":"PSUSA","opinion":"2023-09-14","decision":"2023-11-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - brexucabtagene autoleucel"}, {"id":"N/0030","type":"N","opinion":"2023-01-17","decision":"2023-10-09","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0026","type":"IB","opinion":"2022-09-21","decision":"2023-10-09","affects":["Annex II"],"codes":["B.II.g.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"II/0019","type":"II","opinion":"2022-06-23","decision":"2022-09-02","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the safety and efficacy information based on 24-month follow-up data from all treated patients in cohort 1 of the pivotal clinical study, KTE-C19-102 (ZUMA-2); a Phase 2, multicenter, open-label study evaluating the safety and efficacy of KTE-X19 in subjects with relapsed or refractory (r/r) mantle cell lymphoma (MCL). This submission is in fulfilment of the specific obligation (SOB 004) to confirm the long-term efficacy and safety of Tecartus in adult patients with relapsed/refractory (r/r) MCL. As a consequence Annex II E has been updated with deletion of the fulfilled SOB."}, {"id":"II/0008/G","type":"II","opinion":"2022-07-21","decision":"2022-09-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.d.1.z","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Group of variations including and extension of indication to include treatment of adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) for Tecartus and a type IB variation to change the Drug Product Dose specification for the new indication. As a consequence, sections 2.2, 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. Annex II is updated to reflect the new Specific Obligations for the new indication. The Package Leaflet and Labelling are updated in accordance. Version 1.1 of the RMP has also been submitted. Furthermore, the PI is brought in line with the latest QRD template."}, {"id":"IAIN/0023","type":"IAIN","opinion":"2022-04-21","decision":"2022-09-02","affects":["SmPC","Labelling","PL"],"codes":["A.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in name of the AS or of an excipient"}, {"id":"WS/2206","type":"WS","opinion":"2021-12-16","decision":"2022-01-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC and Annex IID in order to add statements for the use of Tecartus and Yescarta exceptionally during shortage of tocilizumab following the \"CAT recommendation for the use of CAR-T cell-based therapies in EU during shortages of tocilizumab\". The RMPs for both products are updated accordingly (version 1.2 for Tecartus and version 5.2 for Yescarta). The update of the RMPs for both products (version 1.2 for Tecartus and version 5.2 for Yescarta)"}, {"id":"N/0011","type":"N","opinion":"2021-09-17","decision":"2022-01-24","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "brigatinib__alunbrig": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/alunbrig-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"II/0056","type":"II","opinion":"2025-03-13","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from Brigatinib-5007 study listed as a category 3 study in the RMP. This is a non-interventional cohort study to provide real-world evidence of the occurrence of early-onset pulmonary events in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer treated with brigatinib:"}, {"id":"R/0049","type":"R","opinion":"2023-05-25","decision":"2023-07-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0037","type":"II","opinion":"2022-02-17","decision":"2022-10-14","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study AP26113-13-301 listed as a PAES in the Annex II; this is a randomised, open-label, multicentre phase III study comparing brigatinib versus crizotinib in patients with advanced ALK-positive NSCLC who have not previously received ALK-directed therapy; The RMP version 6.0 has also been submitted."}, {"id":"II/0034","type":"II","opinion":"2022-01-13","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on photosensitivity based on a report of cumulative evidence for an association between exposure to brigatinib and subsequent development of photosensitivity reaction; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make a minor editorial change in section 4.8 of the SmPC."}, {"id":"II/0033/G","type":"II","opinion":"2022-01-27","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.1"],"scope":"Update of section 4.5 of the SmPC in order to add drug-drug interaction information about the effect of brigatinib on the pharmacokinetics of a sensitive cytochrome P450 3A substrate (midazolam) in patients with ALK-positive or ROS1-positive solid tumours based on a clinical study report (Study 1001). Update of section 4.4 and 4.5 of the SmPC in order to update drug-drug interaction information regarding concomitant treatment with moderate CYP3A inducers based on results of previously submitted studies (physiologically-based pharmacokinetic (PBPK) report and PBPK report addendum). Update section 5.1 of the SmPC in order to amend the ATC code."}, {"id":"IA/0039","type":"IA","opinion":"2021-09-15","decision":"2022-10-14","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"IB/0018","type":"IB","opinion":"2020-07-06","decision":"2021-07-05","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0026/G","type":"IAIN","opinion":"2020-12-11","decision":"2021-07-05","affects":["Annex II","PL"],"codes":["B.II.b.1.b","B.II.b.1.a","B.II.b.2.c.2","B.II.e.4.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Change in shape or dimensions of the container or closure (immediate packaging) - Non-sterile medicinal products"}, {"id":"IAIN/0023","type":"IAIN","opinion":"2020-09-15","decision":"2021-07-05","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0003","type":"II","opinion":"2020-02-27","decision":"2020-04-01","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor for Alunbrig. The addition of a new indication is supported by data from Study 301 (AP26113-13-301; ALTA 1L), a phase 3, randomized, open label, comparative, multicenter, international phase 3 study. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. In addition, the due date for the submission of the Annex II condition has been updated. The Package leaflet and labelling are updated in accordance. The RMP version 5.3 has been approved."}, {"id":"IB/0001/G","type":"IB","opinion":"2018-12-18","decision":"2019-11-19","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "cabozantinib__cabometyx": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/cabometyx-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/cabometyx-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000372830","type":"IB","opinion":"2026-10-14","decision":null,"affects":["SmPC"],"codes":["C.3.z"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To update section 5.1 of the SmPC to replace the current paediatric deferment statement with wording reflecting the completion of the paediatric studies agreed under PIP EMEA-001143-PIP01-11 and the current status of the paediatric development programme. In addition to this SmPC update, the MAH requests the incorporation of the outcome of the positive full Paediatric Investigation Plan (PIP) compliance opinion into the Marketing Authorisation and the issuance of a PIP compliance statement for CABOMETYX within the same procedure."}, {"id":"EMA/VR/0000271719","type":"II","opinion":"2026-01-15","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on cardiac failure following the recent update of the CCSI to version 10."}, {"id":"EMA/VR/0000286913","type":"IB","opinion":"2025-08-22","decision":"2025-10-24","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"To update Section 4.2 of the Cabometyx SmPC to reflect the approval of the subcutaneous formulation of Nivolumab for use in combination treatment of advanced renal cell carcinoma, following procedure EMEA/H/C/003985/X/0144 In addition, the MAH took the opportunity to implement editorial changes, to align the wording of ‘cabozantinib + nivolumab’ throughout the SmPC, and removed the local representative for UK (NI) in the PL in alignment with the QRD template."}, {"id":"EMA/VR/0000263255","type":"IAIN","opinion":"2025-04-15","decision":"2025-10-24","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"II/0040","type":"II","opinion":"2025-06-19","decision":"2025-07-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"IB/0037","type":"IB","opinion":"2023-10-06","decision":"2024-09-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0032","type":"II","opinion":"2023-06-08","decision":"2023-10-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Vanishing Bile Duct Syndrome (VBDS), to add embolism arterial to the list of adverse drug reactions (ADRs) with frequency Uncommon and to add vanishing bile duct syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the cumulative review of the global safety database and literature search. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0029","type":"II","opinion":"2022-09-15","decision":"2023-10-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"SmPC sections 4.4 and 4.8 have been updated as follows: In differentiated thyroid carcinoma, dose reductions and dose interruptions occurred in 67% and 71% respectively of cabozantinib treated patients in the clinical trial (COSMIC-311). Two dose reductions were required in 33% of patients. The median time to first dose reduction was 57 days and to first dose interruption was 38.5 days. The most common serious adverse drug reactions in the DTC population (≥1% incidence) are diarrhoea, pleural effusion, pneumonia, pulmonary embolism, hypertension, anaemia, deep vein thrombosis, hypocalcemia, osteonecrosis of jaw, pain, palmar-plantar erythrodysaesthesia syndrome, vomiting and renal impairment."}, {"id":"IB/0035","type":"IB","opinion":"2023-06-19","decision":"2023-10-04","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"PSUSA/00010180/202111","type":"PSUSA","opinion":"2022-07-21","decision":"2022-09-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"II/0023","type":"II","opinion":"2022-03-24","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include monotherapy treatment of adults and adolescent patients aged 12 years and older, with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine (RAI) who have progressed during or after prior systemic therapy for CABOMETYX; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. The MAH also took the opportunity to update the local representative for Spain. Version 6.1 of the RMP has also been submitted."}, {"id":"IB/0025","type":"IB","opinion":"2021-11-09","decision":"2022-04-29","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"IB/0021","type":"IB","opinion":"2021-06-25","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IA/0026","type":"IA","opinion":"2021-10-19","decision":"2022-04-29","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0018","type":"R","opinion":"2021-02-25","decision":"2021-04-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0017","type":"II","opinion":"2021-02-25","decision":"2021-03-26","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include in combination with nivolumab first line treatment of advanced renal cell carcinoma for CABOMETYX; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 5.1 of the RMP has also been submitted."}, {"id":"IB/0015/G","type":"IB","opinion":"2020-10-22","decision":"2021-03-26","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.1.e","B.II.b.2.a","B.II.b.2.c.2","B.II.b.3.a","B.II.d.2.a","B.II.f.1.e","B.II.b.4.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing."}, {"id":"N/0010","type":"N","opinion":"2019-12-20","decision":"2020-07-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0012","type":"II","opinion":"2020-04-30","decision":"2020-07-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of section 4.4 of the SmPC to include the risk of Osteonecrosis as a warning. Update of Section 4.8 of the SmPC based on the Company Core Safety Information: - to add Dysphagia and Hyperkeratosis to the existing ADR, - to replace Peripheral sensory neuropathy by Peripheral neuropathy in order to reflect the broader medical concept and to add DVT (Deep vein thrombosis) to the existing ADR venous thrombosis in order to alert prescribers to the most frequently reported type of venous thrombosis. Changes to the frequency categorisation of some ADRs are also proposed based on new pooled data."}, {"id":"IAIN/0011","type":"IAIN","opinion":"2019-10-30","decision":"2020-07-31","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0009/G","type":"IAIN","opinion":"2019-08-19","decision":"2020-07-31","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0014","type":"IA","opinion":"2020-06-05","decision":"2020-07-31","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Change in type/addition of a new container - Deletion of an immediate packaging container without a complete deletion of a strength or pharmaceutical form"}, {"id":"PSUSA/00010180/201811","type":"PSUSA","opinion":"2019-06-27","decision":"2019-06-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"II/0005","type":"II","opinion":"2018-09-20","decision":"2018-11-12","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to add Cabometyx as monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated with safety and efficacy information. The package leaflet and the risk management plan (version 4.2) are updated accordingly."}, {"id":"PSUSA/00010180/201711","type":"PSUSA","opinion":"2018-06-28","decision":"2018-08-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"II/0003","type":"II","opinion":"2018-03-22","decision":"2018-05-08","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of indication to include for the treatment of advanced renal cell carcinoma the ‘treatment-naïve adults with intermediate or poor risk’ for CABOMETYX; as a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The package Leaflet and risk management plan (version 3.2) are also updated accordingly. In addition, the marketing authorisation holder took the opportunity to make some editorial changes in the product information."}, {"id":"II/0002/G","type":"II","opinion":"2017-11-09","decision":"2018-05-08","affects":["SmPC","Annex II"],"codes":["C.I.4","C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1","5.3"],"scope":"1) C.I.4 (type II) Update of section 5.1 of the SmPC to reflect the final study results from clinical study XL184-308: A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects with Metastatic Renal Cell Carcinoma that has Progressed after Prior VEGFR Tyrosine Kinase Inhibitor Therapy, to fulfil the condition to the marketing authorisation listed as a PAES in the Annex II. The RMP version 2.0 has also been submitted. 2) C.I.4 (type II) Update of section 5.3 of the SmPC to reflect the final study results from non-clinical study XL184-NC-036: 104-Week Oral Gavage Carcinogenicity and Toxicokinetic Study with Cabozantinib (XL184) in Rats."} ] }, "cabozantinib__cometriq": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/cometriq-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/cometriq-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000372831","type":"IB","opinion":"2026-10-13","decision":null,"affects":["SmPC"],"codes":["C.3.z"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"To proposes the deletion from section 5.1 of the COMETRIQ SmPC of the following standard QRD statement: “The obligation to submit the results of studies with COMETRIQ in one or more subsets of the paediatric population in the treatment of malignant solid tumours has been deferred (see section 4.2 for information on paediatric use)”, following completion of the agreed Paediatric Investigation Plan for cabozantinib (EMEA-001143-PIP01-11) and the subsequent positive full PIP compliance check adopted by the PDCO, the above statement referring to a deferral is no longer applicable."}, {"id":"EMA/VR/0000370340","type":"IA","opinion":"2026-09-23","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.3.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Minor change in the manufacturing process; E. Administrative Changes - E.5 Deletion of manufacturing sites for an active substance, intermediate or finished product, storage of master and/or working cell bank, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier)"}, {"id":"EMA/VR/0000271719","type":"II","opinion":"2026-01-15","decision":"2026-05-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on cardiac failure following the recent update of the CCSI to version 10."}, {"id":"EMA/VR/0000263255","type":"IAIN","opinion":"2025-04-15","decision":"2026-05-26","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"EMA/R/0000316559","type":"R","opinion":"2026-03-26","decision":"2026-05-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation."}, {"id":"II/0053","type":"II","opinion":"2023-09-14","decision":"2024-09-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add embolism arterial to the list of adverse drug reactions (ADRs) with frequency Uncommon based on literature search. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"PSUSA/00010180/202111","type":"PSUSA","opinion":"2022-07-21","decision":"2022-09-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"II/0049","type":"II","opinion":"2022-03-31","decision":"2022-09-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to amend an existing warning on hypertension and add hypertensive crisis to the list of adverse drug reactions (ADRs) with frequency not known based on literature review and post-marketing and clinical data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0044","type":"II","opinion":"2021-07-22","decision":"2021-09-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.1","4.4","5.1"],"scope":"Update of section 5.1 of the SmPC based on the final results from study XL184-401 (EXAMINER) (SOB 001), a randomised, double-blind study to evaluate the efficacy and safety of cabozantinib (XL184) at 60 mg/day compared to a 140 mg/day in progressive, metastatic medullary thyroid cancer patients and as a consequence update of annex II in order to delete SOB 001. With the fulfilment of SOB 001 the MAH is requesting for the Cometriq MA to no longer be subject to specific obligations. The package leaflet is updated accordingly. The updated RMP version 5.5 has also been submitted."}, {"id":"IAIN/0045/G","type":"IAIN","opinion":"2021-05-17","decision":"2021-08-12","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","B.I.d.1.c","A.5.b","B.II.b.2.a","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Stability of AS - Change in the re-test period/storage period or storage conditions - Change to an approved stability protocol; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place."}, {"id":"IA/0043/G","type":"IA","opinion":"2021-03-04","decision":"2021-08-12","affects":["SmPC","Annex II","PL"],"codes":["A.7","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0042","type":"R","opinion":"2020-12-10","decision":"2021-02-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0033","type":"N","opinion":"2019-12-20","decision":"2021-02-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0035","type":"II","opinion":"2020-04-30","decision":"2021-02-11","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of section 4.2 to introduce a clarification in alignment with Cabometyx; update of section 4.4 of the SmPC to include the addition of the risk of diarrhoea and additional text to the existing risks of thromboembolic events, haemorrhage, wound complications and Posterior reversible encephalopathy syndrome (PRES). Update of Section 4.8 of the SmPC, based on the Company Core Safety Information, to add DVT (Deep vein thrombosis) to the existing ADR venous thrombosis in order to alert prescribers to the most frequently reported type of venous thrombosis. Changes to the frequency categorisation of some ADRs are also proposed based on new pooled data."}, {"id":"IB/0039","type":"IB","opinion":"2020-06-26","decision":"2021-02-11","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"R/0032","type":"R","opinion":"2019-12-12","decision":"2020-02-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0034","type":"IAIN","opinion":"2019-10-30","decision":"2020-02-21","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010180/201811","type":"PSUSA","opinion":"2019-06-27","decision":"2019-08-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"IAIN/0031/G","type":"IAIN","opinion":"2019-06-25","decision":"2019-08-23","affects":["Annex II","PL"],"codes":["A.4","B.II.b.2.a","B.II.b.2.c.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing"}, {"id":"R/0029","type":"R","opinion":"2019-01-31","decision":"2019-03-28","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010180/201711","type":"PSUSA","opinion":"2018-06-28","decision":"2018-08-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"R/0027","type":"R","opinion":"2017-11-09","decision":"2018-01-08","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0024","type":"II","opinion":"2017-01-26","decision":"2018-01-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC to reflect the results of the final study report of the non-clinical study (XL184-NC-036) assessing the carcinogenicity potential in rat. In addition, the risk management plan (RMP) is being updated accordingly. The requested variation proposed amendments to the Summary of Product Characteristics and to the Risk Management Plan (RMP)."}, {"id":"PSUSA/00010180/201603","type":"PSUSA","opinion":"2016-10-13","decision":"2016-12-12","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cabozantinib"}, {"id":"T/0023","type":"T","opinion":"2016-09-05","decision":"2016-09-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing authorisation transfer from TMC Pharma Service Limited to Ipsen Pharma. Transfer of Marketing Authorisation"}, {"id":"II/0018","type":"II","opinion":"2015-12-17","decision":"2016-09-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC with the results from the carcinogenicity study in mice. Furthermore, the MAH took the opportunity to align the PI with the latest QRD template version 9.1."}, {"id":"R/0017","type":"R","opinion":"2015-11-19","decision":"2016-01-11","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0015","type":"II","opinion":"2015-06-25","decision":"2016-01-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC following the results of study XL184-301. The Risk Management Plan version 3 and the Package Leaflet and RMP are updated accordingly."}, {"id":"II/0013/G","type":"II","opinion":"2015-04-23","decision":"2015-05-27","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of non-clinical study reports from Enterohepatic recirculation evaluation in dogs (XL184-NC-045) and Enterohepatic recirculation evaluation in rats (XL184-NC-046). The requested group of variations proposed no amendments to the Product Information."}, {"id":"II/0011/G","type":"II","opinion":"2015-04-23","decision":"2015-05-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC further to the results of studies conducted to assess the pharmacokinetics of cabozantinib in subjects with impaired hepatic and renal function. The PL is proposed to be updated accordingly. The requested group of variations proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"II/0005/G","type":"II","opinion":"2014-12-18","decision":"2015-05-27","affects":["SmPC","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC with regards to concomitant use with MRP2 inhibitors further to the results of Study XL184-NC-039 evaluating Cabozantinib as a Substrate and Inhibitor of a Panel of Human Drug Transporters (MEA 006). The Package leaflet is updated accordingly; Submission of the results of Study XL184-NC-043 assessing cabozantinib as an inhibitor of human MATE1 and MATE2-K-mediated transport (MEA 007); Submission of the results of Study XL184-NC-048 assessing cabozantinib as an inhibitor of human OAT3, MATE1, and MATE2-K-mediated transport."}, {"id":"R/0009","type":"R","opinion":"2014-11-20","decision":"2015-01-19","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0006","type":"II","opinion":"2014-09-25","decision":"2015-01-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of section 4.4 of the SmPC to delete the warning on concomitant use with proton pump inhibitors further to the results of a drug-drug Interaction Study XL184-018 with medicinal products affecting gastric pH (esomeprazole and Famotidine) (MEA 004). The Package leaflet is updated accordingly. The MAH also took the opportunity to make a correction in section 4.5 and the PL."}, {"id":"II/0004/G","type":"II","opinion":"2014-09-25","decision":"2015-01-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0003","type":"IB","opinion":"2014-06-17","decision":"2015-01-19","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"To extend the shelf-life of the finished product"}, {"id":"IB/0002","type":"IB","opinion":"2014-05-28","decision":"2015-01-19","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IA/0001","type":"IA","opinion":"2014-04-28","decision":"2015-01-19","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "camizestrant__etcamah": { "source": [], "procedures": [] }, "capivasertib__truqap": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/truqap-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/truqap-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000320727","type":"II","opinion":"2026-03-12","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8, and 5.1 of the SmPC in order to change posology recommendations in Table 3, amend an existing warning for Hyperglycaemia, update the summary of safety profile & description of selected adverse reaction, update efficacy based on final results from study CAPItello-291 listed as a PAM Recommendation PAES;"}, {"id":"EMA/VR/0000284700","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update non-clinical information, based on results of the 2-Year Oral (Gavage) Carcinogenicity Study in the Rat (Study 8003384)."}, {"id":"EMA/VR/0000272181","type":"II","opinion":"2025-07-24","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to amend the current wording pertaining to the adverse drug reaction (ADR)"}, {"id":"II/0002","type":"II","opinion":"2025-01-23","decision":"2025-02-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the clinical efficacy information to reflect a new overall survival (OS) interim analysis pertaining to study D3615C00001 (CAPItello-291) in order to fulfil REC 004; this is a phase III double-blind randomised study assessing the efficacy and safety of capivasertib + fulvestrant versus placebo + fulvestrant as treatment for locally advanced (inoperable) or metastatic Hormone Receptor positive, Human Epidermal Growth Factor Receptor 2 negative (HR+/HER2−) breast cancer following recurrence or progression on or after treatment with an aromatase inhibitor."}, {"id":"II/0001","type":"II","opinion":"2025-01-30","decision":"2025-02-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to update the posology recommendation and the warning regarding Diabetic Ketoacidosis (DKA) and to add it to the list of adverse drug reactions (ADRs) with a frequency “uncommon”, based on a safety review. The Package Leaflet is updated accordingly. The RMP version 2 has also been submitted. In addition, the MAH also took the opportunity to remove post authorisation measures (PAMs) which were incorrectly added to Annex II.D at time of granting of the Marketing Authorisation, to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template version 10.4."} ] }, "capmatinib__tabrecta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tabrecta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tabrecta-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"II/0016","type":"II","opinion":"2025-03-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update information on based on the results of the clinical study CINC280A2201 'GEOMETRY mono-1' and add 'body temperature increased' to the list of adverse drug reactions (ADRs) with frequency 'very common'. CINC280A2201 is a global, multi-cohort, non-randomized, open-label Phase II study designed to evaluate the efficacy and safety of single-agent capmatinib in adult patients with a MET exon 14 (METex14) skipping mutation, advanced non-small cell lung cancer (NSCLC). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"IB/0017/G","type":"IB","opinion":"2025-02-07","decision":null,"affects":["SmPC"],"codes":["B.II.b.3.z","B.II.a.3.a.1","B.II.c.1.z","B.II.b.3.a","B.II.b.4.b","B.II.b.4.a","B.II.b.5.z","B.II.e.1.a.1","B.II.e.2.b","B.II.b.1.e","B.II.b.2.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Control/testing takes place Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0015","type":"IAIN","opinion":"2024-12-04","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0002","type":"II","opinion":"2022-12-01","decision":"2023-11-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add hypersensitivity to the list of adverse drug reactions (ADRs) with frequency uncommon, based on cumulative assessment of hypersensitivity cases in studies CINC280A2201, CINC280X1101, CINC280X2102, CINC280A2108, CINC280A2103 (post-DDI phase only), and CINC280A2105 (post-DDI phase only) and MAH global safety database. The Package Leaflet is updated accordingly"} ] }, "carfilzomib__kyprolis": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kyprolis-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kyprolis-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000322790","type":"II","opinion":"2026-06-25","decision":null,"affects":["SmPC","PL"],"codes":["C.I.13","C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"A grouped application consisting of: Update of sections 4.2 and 5.1 of the SmPC in order to update paediatric information based on final results from study 20140106. This is a Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and to update the list of local representatives in the Package Leaflet. Submission of the final report from study 20180065."}, {"id":"II/0058","type":"II","opinion":"2023-12-14","decision":null,"affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"II/0051/G","type":"II","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"The ATC code of the product is updated C.I.4, Update of section 4.2 of the SmPC in order to modify administration instructions of daratumumab when Kyprolis is dosed in combination with daratumumab and dexamethasone, based on results from efficacy and safety studies MMY2040 (ongoing phase 2), MMY1001 (completed phase 1b) and CANDOR (ongoing phase 3). are recommended for approval. Amendments to the marketing authorisation In view of the data submitted with the group of variations, amendments to Annex(es) I are recommended."}, {"id":"PSUSA/00010448/202007","type":"PSUSA","opinion":"2021-02-25","decision":"2021-04-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - carfilzomib"}, {"id":"II/0045","type":"II","opinion":"2020-11-12","decision":"2020-12-17","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of existing indication to include combination of Kyprolis with daratumumab and dexamethasone; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 12.0 of the RMP has also been submitted."}, {"id":"R/0044","type":"R","opinion":"2020-04-30","decision":"2020-06-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0043","type":"II","opinion":"2020-04-17","decision":"2020-06-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include cardiomyopathy as a new adverse drug reaction with uncommon frequency following a signal evaluation triggered by a request from the Therapeutic Goods Administration (TGA) Australian authority. The RMP version 11.0 has also been submitted. In addition, the MAH took the opportunity to make some minor editorial changes to the PI."}, {"id":"PSUSA/00010448/201901","type":"PSUSA","opinion":"2019-09-19","decision":"2019-11-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - carfilzomib"}, {"id":"N/0036","type":"N","opinion":"2019-05-22","decision":"2019-11-14","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0038","type":"II","opinion":"2019-09-19","decision":"2019-11-14","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":["6.6"],"scope":"Update of section 6.6 of the SmPC with information regarding the handling and preparation of Kyprolis. Labelling and PL are updated accordingly."}, {"id":"PSUSA/00010448/201807","type":"PSUSA","opinion":"2019-02-28","decision":"2019-04-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - carfilzomib"}, {"id":"II/0030","type":"II","opinion":"2018-09-20","decision":"2018-11-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to include a warning of the increased risk of cardiac failure in Asian patients treated with carfilzomib based on postmarketing experience and three phase 3 randomized-controlled studies (CLARION-Study 2011-003; ENDEAVOR-Study 20130398 and A.R.R.O.W.-Study 20140355). In addition, the Marketing authorisation holder (MAH) took the opportunity to propose few minor typographical changes to SmPC."}, {"id":"II/0025","type":"II","opinion":"2018-04-26","decision":"2018-11-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"A pre-planned overall survival (OS) analysis was performed after 246 deaths in the Kyprolis, lenalidomide and dexamethasone (KRd) arm and 267 deaths in the lenalidomide and dexamethasone (Rd) arm. The median follow-up was approximately 67 months. A statistically significant advantage in OS was observed in patients in the KRd arm compared to patients in the Rd arm. Patients in the KRd arm had a 21% reduction in the risk of death compared with those in the Rd arm (HR = 0.79; 95% CI: 0.67, 0.95; p value = 0.0045). The median OS improved by 7.9 months in patients in the KRd arm compared with those in the Rd arm (see sections 5.1 of the SmPC for further details)."}, {"id":"IG/0946","type":"IG","opinion":"2018-06-04","decision":"2018-11-22","affects":["PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010448/201707","type":"PSUSA","opinion":"2018-02-22","decision":"2018-04-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - carfilzomib PSUSA/10448/201707."}, {"id":"II/0017/G","type":"II","opinion":"2018-01-25","decision":"2018-04-19","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Results from the 2nd interim analysis of overall survival (OS) for the ENDEAVOR study confirm previous findings and provide a statistically significant and clinically relevant result. The study thus met the objective for OS, and therefore the ENDEAVOR Overall Survival 2nd interim analysis CSR (53.4% data maturity) is considered the final OS analysis. Section 5.1 of SmPC has been updated to reflect this analysis of OS (2nd IA). Results in terms of the secondary endpoint of peripheral neuropathy (incidence of grade 2 of higher peripheral neuropathy) continue showing a clinically relevant reduction of events. Regarding safety, updated data confirm previous findings."}, {"id":"IG/0853","type":"IG","opinion":"2017-11-10","decision":"2018-04-19","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010448/201701","type":"PSUSA","opinion":"2017-09-14","decision":"2017-11-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - carfilzomib"}, {"id":"IAIN/0011","type":"IAIN","opinion":"2017-03-10","decision":"2017-11-15","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0007/G","type":"II","opinion":"2016-11-10","decision":"2016-12-12","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Marketing Authorisation Holder has submitted information on a dedicated renal impairment study (Study CFZ001) conducted in subjects with relapsed multiple myeloma and on a dedicated hepatic impairment study data Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data (Study CFZ002) conducted in subjects with relapsed or progressive advanced malignancies (solid tumours or hematologic malignancies)."}, {"id":"II/0006/G","type":"II","opinion":"2016-08-04","decision":"2016-12-12","affects":["SmPC","Labelling","PL"],"codes":["B.II.b.3.a","B.II.b.3.b","B.II.b.4.d","B.II.e.4.c","B.II.e.5.c","B.II.e.6.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process; Change in the manufacturing process of the finished or intermediate product - Substantial changes to a manufacturing process that may have a significant impact on the quality, safety and efficacy of the medicinal product; Change in the batch size (including batch size ranges) of the finished product - The change relates to all other pharmaceutical forms manufactured by complex manufacturing processes; Change in shape or dimensions of the container or closure (immediate packaging) - Sterile medicinal products."}, {"id":"IB/0008","type":"IB","opinion":"2016-11-08","decision":"2016-12-12","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0004/G","type":"II","opinion":"2016-04-28","decision":"2016-06-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add information on haemorrhagic events and update of sections 4.4 and 4.6 of the SmPC in order to add information on venous thrombolic events; the Package Leaflet and RMP are updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the RMP with the request to better characterize infections in patients with relapsed / refractory multiple myeloma requested during MAA review."}, {"id":"II/0002/G","type":"II","opinion":"2016-02-25","decision":"2016-06-29","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update information on the potential for carfilzomib to inhibit UGT1A1 and UGT2B7 based on study 121863. In addition, the Marketing authorisation holder (MAH) submitted two other in-vitro drug-drug interaction (DDI) studies (121856 and 121939) on major metabolites M14, M15 and M16 to address their inhibitory and induction effects on CYP. Furthermore the MAH took the occasion to introduce an editorial change to section 4.5 of the SmPC."}, {"id":"II/0001/G","type":"II","opinion":"2016-05-26","decision":"2016-06-29","affects":["SmPC","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2","6.6"],"scope":"Extension of Indication to include new indication for Kyprolis to be used with either lenalidomide and dexamethasone or dexamethasone alone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and the RMP (version 6.0) is updated in accordance. In addition, the Marketing authorisation holder (MAH) updated section 6.6 of the SmPC to include the option to administer Kyprolis in a 100 mL intravenous bag containing 5% glucose solution for injection in line with the extension of indication part of this variation."} ] }, "catumaxomab__korjuny": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/korjuny-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000304947","type":"II","opinion":"2026-03-19","decision":null,"affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study concerning the validation of quantification of EpCAM-positive cells in malignant ascites samples for EpCAM CytoDetect Assay implementation using HO-3 primary anti-body to fulfil commitment given during the Marketing Authorisation Application (EMEA/H/C/005697)."}, {"id":"EMA/VR/0000297256","type":"IAIN","opinion":"2025-09-23","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000276206","type":"IB","opinion":"2025-06-23","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation"}, {"id":"EMA/VR/0000255947","type":"IAIN","opinion":"2025-03-26","decision":"2025-05-15","affects":["SmPC","PL"],"codes":["C.I.12"],"outcome":"accepted","kind":"other","sections":[],"scope":"To include in the Product Information the black symbol and explanatory statement for medicinal products that are subject to additional monitoring."}, {"id":"EMA/T/0000258313","type":"T","opinion":"2025-03-28","decision":"2025-05-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from Lindis Biotech GmbH to Atnahs Pharma Netherlands B.V."} ] }, "cemiplimab__libtayo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/libtayo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/libtayo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000264999","type":"II","opinion":"2025-10-16","decision":"2025-11-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","6.6"],"scope":"Extension of indication to include treatment of adjuvant treatment of adult patients with Cutaneous Squamous Cell Carcinoma (CSCC) at high risk of recurrence after surgery and radiation for LIBTAYO, based on interim results from study R2810-ONC-1788; this is a phase 3, randomized, placebo-controlled, double-blind study of adjuvant cemiplimab versus placebo after surgery and radiation therapy in patients with high risk CSCC; As a consequence, sections 4.1, 4.2, 4.8, 5.1, and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.2 of the RMP has also been submitted."}, {"id":"EMA/VR/0000293784","type":"II","opinion":"2025-11-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4, and 4.8 of the SmPC in order to add a new warning on pancreatitis and add pancreatitis to the list of adverse drug reactions (ADRs) with frequency not known following internal safety signal assessment; the Package Leaflet is updated accordingly. In addition, the MAH has removed the black triangle and additional monitoring status from the SmPC and PL provided with this variation."}, {"id":"PSUSA/00010780/202409","type":"PSUSA","opinion":"2025-05-22","decision":"2025-07-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cemiplimab"}, {"id":"N/0049","type":"N","opinion":"2024-11-01","decision":"2024-12-19","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0039","type":"N","opinion":"2024-01-10","decision":"2024-12-19","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0047","type":"II","opinion":"2024-09-05","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC to update paediatric population information from Study R2810-ONC-1690 (Study 1690) following the outcome of Article 46 procedure (EMA/H/C/004844/P46/011)."}, {"id":"II/0043","type":"II","opinion":"2024-06-20","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC in order to add ‘uveitis’ to the list of adverse drug reactions (ADRs) with frequency rare, based on a safety evaluation report. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor corrections to the efficacy data in section 5.1 of the SmPC based on an erratum for the interim report for study R2810-ONC-1620, as well as to introduce minor editorial and formatting changes to the PI and to update the list of local representatives in the Package Leaflet."}, {"id":"IB/0038/G","type":"IB","opinion":"2024-01-03","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["B.I.d.1.a.4","B.II.f.1.b.3","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IAIN/0045/G","type":"IAIN","opinion":"2024-06-21","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010780/202209","type":"PSUSA","opinion":"2023-04-26","decision":"2023-06-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cemiplimab"}, {"id":"II/0028","type":"II","opinion":"2023-02-23","decision":"2023-03-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include LIBTAYO in combination with platinum-based chemotherapy for the first-line treatment of adult patients with locally advanced NSCLC who are not candidates for definitive chemoradiation or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations; as a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.0 of the RMP has also been agreed."}, {"id":"II/0032","type":"II","opinion":"2022-10-06","decision":"2022-11-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the list of adverse drug reactions (ADRs) and efficacy results for the BCC indication based on the primary analysis data from study R2810-ONC-1620 listed in the Annex II; this is a phase 2 study of cemiplimab in patients with advanced basal cell carcinoma who experienced progression of disease on hedgehog pathway inhibitor therapy or were intolerant of prior hedgehog pathway inhibitor therapy. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0031","type":"II","opinion":"2022-10-06","decision":"2022-11-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the list of adverse drug reactions (ADRs) and efficacy information based on final results from study R2810-ONC-1540 in order to fulfil REC/005; this is a nonrandomized, multicenter, phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0026","type":"II","opinion":"2022-10-13","decision":"2022-11-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"R/0029","type":"R","opinion":"2022-04-22","decision":"2022-07-01","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0030","type":"N","opinion":"2022-02-04","decision":"2022-06-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00010780/202103","type":"PSUSA","opinion":"2021-11-11","decision":"2022-01-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cemiplimab"}, {"id":"IB/0024","type":"IB","opinion":"2021-10-12","decision":"2022-01-07","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0012","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include : LIBTAYO as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI).SmPC sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 have been revised. The PL has been updated accordingly. Version 2.0 of the RMP has been submitted. Annex IID has been revised."}, {"id":"II/0011","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication for LIBTAYO as monotherapy indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) expressing PD-L1 (in ≥ 50% tumour cells), with no EGFR, ALK or ROS1 aberrations based on the results of study R2810-ONC-1624 comparing cemiplimab monotherapy to platinum doublet chemotherapy. The PL is revised accordingly. RMP version 2.0 has been agreed."}, {"id":"N/0013","type":"N","opinion":"2020-11-25","decision":"2021-05-10","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0010/G","type":"II","opinion":"2020-09-10","decision":"2021-05-10","affects":["Annex II"],"codes":["A.4","B.I.a.1.e","B.I.a.1.f","B.I.a.4.z","B.II.b.3.c","B.II.d.1.d","B.II.d.1.e","B.I.b.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place."}, {"id":"IB/0019/G","type":"IB","opinion":"2021-03-08","decision":"2021-05-10","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.5","A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0007","type":"II","opinion":"2020-06-11","decision":"2020-07-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","4.9","5.1","5.2","6.3"],"scope":"Update of sections 4.2, 4.4, 4.8 of the SmPC to amend an existing warning and add new ADRs with frequency uncommon, regarding new safety information in the post marketing setting on the terms “Transplant rejection”, “Graft Versus Host Disease (GVHD)” and “Myositis” and amended relevant recommendations for treatment modification. The MAH took the opportunity to update Section 5.1, based on minor corrections to the efficacy data in the SmPC from study R2810-ONC-1540 (primary analysis for group 2 and 3 dated 09 Jul 2019), considering errors that were revealed in two patient’s data following the completion of the MA."}, {"id":"IAIN/0008","type":"IAIN","opinion":"2020-05-15","decision":"2020-07-31","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010780/201909","type":"PSUSA","opinion":"2020-04-30","decision":"2020-06-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cemiplimab"}, {"id":"IB/0001/G","type":"IB","opinion":"2019-09-06","decision":"2020-05-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1","A.4","A.5.a","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "ceritinib__zykadia": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zykadia-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/zykadia-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000323613","type":"IA","opinion":"2026-01-28","decision":null,"affects":["Annex II","PL"],"codes":["A.5.b","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000293040","type":"IAIN","opinion":"2025-08-26","decision":null,"affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"EMA/VR/0000247426","type":"IA","opinion":"2025-01-30","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000247247","type":"IAIN","opinion":"2025-01-29","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"II/0055","type":"II","opinion":"2024-12-12","decision":null,"affects":["SmPC"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the section 5.1 of the SmPC following the submission of the final report from PAES study LDK378A2303; this is a Phase III, multicenter, randomized, open-label study of oral LDK378 versus standard chemotherapy in adult patients with ALK rearranged (ALK-positive) advanced non-small cell lung cancer who have been treated previously with chemotherapy (platinum doublet) and crizotinib. The RMP (version 18.0) is updated accordingly."}, {"id":"IB/0053/G","type":"IB","opinion":"2024-06-07","decision":"2024-12-12","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.b.1.e","B.II.b.1.b","B.II.b.1.a","B.II.b.2.c.2","B.II.b.4.b","B.II.b.3.z","B.II.c.1.a","B.II.e.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing."}, {"id":"IAIN/0048/G","type":"IAIN","opinion":"2023-12-06","decision":"2024-12-12","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1","B.II.b.1.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Primary packaging site"}, {"id":"R/0042","type":"R","opinion":"2021-12-16","decision":"2022-02-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0041","type":"N","opinion":"2021-09-29","decision":"2022-02-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0034","type":"II","opinion":"2021-03-11","decision":"2022-02-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC in order to reflect the results of study CLDK378A2112 as recommended by the CHMP. The study assesses the steady-state PK of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive NSCLC. The Package Leaflet is updated accordingly. The RMP version 16 has also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1. Other editorial changes include the addition of the Sodium content in the SmPCs and PLs and the removal of the black triangle"}, {"id":"IB/0037/G","type":"IB","opinion":"2021-04-07","decision":"2022-02-16","affects":["Annex II","PL"],"codes":["B.II.e.2.z","B.II.b.1.b","B.II.b.2.c.1","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the immediate packaging of the finished product - Other variation; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Secondary packaging site"}, {"id":"IAIN/0038","type":"IAIN","opinion":"2021-05-28","decision":"2022-02-16","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"To replace a site responsible for batch release of the Zykadia 150 mg hard gelatin capsule (EU/1/15/999/001-003)."}, {"id":"IB/0031/G","type":"IB","opinion":"2020-01-13","decision":"2021-01-14","affects":["SmPC","Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.1.a","B.II.b.2.c.1","B.II.b.4.b","B.II.f.1.b.1","B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Deletion of manufacturing sites; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in the batch size (including batch size ranges) of the finished product - Downscaling down to 10-fold."}, {"id":"X/0025","type":"X","opinion":"2019-01-31","decision":"2019-04-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"II/0026","type":"II","opinion":"2019-01-17","decision":"2019-03-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0016","type":"II","opinion":"2018-05-31","decision":"2018-07-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"The SmPC has been modified to include a recommendation that a dose reduction by approximately one-third is recommended in patients with severe hepatic impairment. Additionally, those patients should be carefully monitored for hepatotoxicity."}, {"id":"T/0024","type":"T","opinion":"2018-05-09","decision":"2018-06-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0015","type":"II","opinion":"2018-03-22","decision":"2018-04-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"The recommended dose of Zykadia is 450 mg taken orally once daily with food at the same time each day. It is important that Zykadia is taken with food to reach the appropriate exposure. Food can range from a light to a full meal. The maximum recommended dose with food is 450 mg taken orally once daily. If vomiting occurs during the course of treatment, the patient should not take an additional dose, but should continue with the next scheduled dose. In case severe or intolerable nausea, vomiting or diarrhoea despite optimal anti emetic or anti diarrhoeal therapy occur, withhold Zykadia until improved, then reinitiate Zykadia with dose reduced by 150 mg."}, {"id":"IAIN/0020","type":"IAIN","opinion":"2017-11-10","decision":"2018-04-23","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"II/0010","type":"II","opinion":"2017-05-18","decision":"2017-07-26","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to"}, {"id":"II/0012","type":"II","opinion":"2017-05-18","decision":"2017-06-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include new indication/population for Zykadia as first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC); as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated to reflect the information based primarily on the supporting study, CLDK378A2301 (ASCEND-4). The Package Leaflet is updated in accordance. The Risk Management Plan version 10.0 was agreed."}, {"id":"II/0006/G","type":"II","opinion":"2017-02-23","decision":"2017-06-23","affects":["SmPC"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC based on the final results of the clinical pharmacology study LDK378A2113 and results of a sub-group evaluating the impact of gastric PH-elevating agents on the steady-state PK, efficacy, and safety of ceritinib in ALK-positive NSCLC patients. The provision of the final CSR for study CLDK378A2113 addresses the post-authorisation measure (PAM) MEA 003. In addition, an updated RMP version 8.0 was agreed during the procedure."}, {"id":"II/0008","type":"II","opinion":"2016-09-15","decision":"2017-03-22","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To update section 5.1 (Pharmacodynamic properties) of the Summary of Product Characteristics as a result of the completion of a study related to a specific obligation of the marketing authorisation."}, {"id":"II/0001","type":"II","opinion":"2015-07-23","decision":"2015-08-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to include posology recommendations and to update the safety information after the MAH’s assessment of the association between the use of ceritinib and acute pancreatitis. The Package Leaflet is updated accordingly. In addition, the updated RMP version 2.5 has been submitted."}, {"id":"IB/0002","type":"IB","opinion":"2015-06-11","decision":"2015-08-25","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "cetuximab__erbitux": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/erbitux-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/erbitux-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000327014","type":"II","opinion":"2026-05-21","decision":"2026-06-25","affects":["SmPC","PL"],"codes":["C.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include in combination with encorafenib and FOLFOX treatment of metastatic colorectal cancer with a BRAF V600E mutation for ERBITUX, based on interim results from study C4221015 (BREAKWATER); this is an open-label, multicenter, 3-arm, randomized phase 3 study of EC alone or in combination with mFOLFOX6 versus standard-of-care chemotherapy in first-line participants with BRAF V600E-mutant mCR. As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 21.1 of the RMP has also been submitted."}, {"id":"EMA/VR/0000326978","type":"II","opinion":"2026-05-21","decision":"2026-06-25","affects":["SmPC","PL"],"codes":["C.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with encorafenib treatment of metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, who have received prior systemic therapy for ERBITUX, based on final results from study ARRAY-818-302 (BEACON-CRC); this is a randomized, open label, 3-arm Phase 3 design that investigated the BRAF inhibitor, encorafenib in combination with cetuximab with or without the mitogen-activated protein kinase (MEK) inhibitor, binimetinib, in patients with BRAF V600E-mutated mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2 of the SmPC are updated."}, {"id":"EMA/VR/0000323569","type":"IA","opinion":"2026-01-28","decision":"2026-06-25","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000291784","type":"II","opinion":"2025-12-04","decision":"2026-06-25","affects":["Annex II","PL"],"codes":["B.II.b.1.z","B.II.b.2.c.3","B.II.e.1.a.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Other changes; Replacement or addition of a manufacturer responsible for importation and/or batch release - Including batch control/testing for a biological/immunological product and any of the test methods performed at that site is a biological / immunological / immunochemical method; Qualitative and quantitative composition - Sterile medicinal products and biological/ immunological medicinal products"}, {"id":"II/0099","type":"II","opinion":"2024-11-14","decision":"2024-12-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.9"],"scope":"Update of sections 4.2, 4.4 and 4.9 of the SmPC in order to introduce every two-weeks (Q2W) dosing regimen as an alternative to the already approved every week (Q1W) dosing regimen for the indications of metastatic colorectal cancer (CRC) and the recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) in combination with platinum-based chemotherapy, based on pharmacokinetic (PK)-TGI-OS modelling and simulations. The Package Leaflet is updated accordingly. The RMP version 19.1 has also been submitted. In addition, the MAH took the opportunity to introduce minor changes to the Product Information."}, {"id":"II/0098/G","type":"II","opinion":"2024-05-23","decision":"2024-12-19","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.a.1.j","B.I.c.1.c","B.I.a.3.a","B.I.a.2.a","B.I.a.4.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Replacement or addition of a site where batch control/testing takes place and any of the test method at the site is a biol/immunol method; Change in immediate packaging of the AS - Liquid ASs (non sterile); Change in batch size (including batch size ranges) of AS or intermediate - Up to 10-fold increase compared to the originally approved batch size."}, {"id":"IA/0101/G","type":"IA","opinion":"2024-08-08","decision":"2024-12-19","affects":["Annex II"],"codes":["A.7","B.II.b.3.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process"}, {"id":"II/0102","type":"II","opinion":"2024-12-12","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on results from study CALGB/SWOG 80405; this is a phase 3 trial of irinotecan/5-fu/leucovorin or oxaliplatin/5-fu/leucovorin with bevacizumab, or cetuximab (C225), or with the combination of bevacizumab and cetuximab for patients with KRAS wild-type untreated metastatic adenocarcinoma of the colon or rectum, with efficacy as primary objective."}, {"id":"IA/0093","type":"IA","opinion":"2022-05-25","decision":"2023-04-24","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0087","type":"N","opinion":"2020-01-06","decision":"2020-06-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0085/G","type":"IAIN","opinion":"2019-07-12","decision":"2020-06-25","affects":["Annex II","PL"],"codes":["A.4","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"T/0084","type":"T","opinion":"2019-05-03","decision":"2019-05-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0077","type":"N","opinion":"2017-06-02","decision":"2019-05-22","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0082","type":"II","opinion":"2018-10-18","decision":"2019-05-22","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC to amend existing warning and safety information on Interstitial lung disease (ILD). The RMP (version 19.0) is updated accordingly and also to include changes recommended as part of procedure EMEA/H/C/PSUSA/00000635/201709. The MAH also took the opportunity to make a minor correction to the Annex II of the Product Information"}, {"id":"N/0071","type":"N","opinion":"2014-11-20","decision":"2014-12-05","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0066","type":"II","opinion":"2014-06-26","decision":"2014-12-05","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with efficacy data by RAS (KRAS and NRAS) tumour status from the CRYSTAL (EMR 62 202-013) and FIRE3 studies"}, {"id":"II/0059","type":"II","opinion":"2013-12-19","decision":"2014-12-05","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to amend administration recommendations and expand on the existing warning related to infusion-related reactions in the course of Erbitux treatment. Section 4.8 of the SmPC is also amended with deletion of information related to infusion reactions, as this information is being reflected in section 4.4 instead and a cross-reference to section 4.4 is being introduced. In addition, a minor deletion is made in section 4.2 of the SmPC. The Package Leaflet is updated accordingly."}, {"id":"IB/0065/G","type":"IB","opinion":"2014-03-28","decision":"2014-12-05","affects":["SmPC"],"codes":["B.I.d.1.c","B.II.f.1.b.5","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period or storage conditions - Change to an approved stability protocol; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Stability of FP - Change to an approved stability protocol"}, {"id":"II/0062","type":"II","opinion":"2013-11-21","decision":"2013-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","5.1"],"scope":"Restriction of the indication for the treatment of colorectal cancer to patients with wild-type RAS tumours in follow-up to CHMP request As a consequence, sections 4.1 and 5.1 of the SmPC are updated. In addition, relevant safety information on the use of Erbitux in patients with mutant RAS tumours is updated in accordance in sections 4.2, 4.3 and 4.4 of the SmPC. Conditions are added in Annex II for submission of results of the CRYSTAL and FIRE III studies by RAS status and of an RMP update in consequence to the amended indication. The Package Leaflet is updated in accordance. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"II/0058","type":"II","opinion":"2013-02-21","decision":"2013-12-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to amend the existing warning on skin reactions and the description of these, respectively, with the addition of necrotising fasciitis as a form of skin reaction that has been reported during Erbitux treatment. This updated safety information was identified following a search for relevant cases in the MAH’s Global Safety Database."}, {"id":"II/0057","type":"II","opinion":"2012-12-13","decision":"2013-12-18","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to amend the severity of mucositis in the course of Erbitux treatment from 'mild to moderate' to 'in some cases severe' following an increased number of relevant cases in the Investigator Sponsored Trial PETACC-8. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make a minor editorial change to the SmPC, Labelling and PL."}, {"id":"II/0052/G","type":"II","opinion":"2012-07-19","decision":"2012-08-30","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.4.b","B.II.e.5.b","C.I.7.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To add an alternative stopper. - To delete the 50 mg/10 ml (EU/1/04/281/002) and 250 mg/50 ml (EU/1/04/281/004) presentations of the concentration 5 mg/ml solution for infusion. - To delete the concentration 2 mg/ml solution for infusion (EU/1/04/281/001)"}, {"id":"II/0048","type":"II","opinion":"2011-12-15","decision":"2012-02-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with 5-year overall survival data from study EMR 62 202-006 (Erbitux in combination with radiation therapy in locally advanced squamous cell cancer of the head and neck). Furthermore, the MAH took the opportunity to update the PL in line with the SmPC regarding the warnings and recommendations on cardiovascular and eye disorders in the course of Erbitux treatment. Finally, the PI was brought in line with the latest QRD template (version 8.1, October 2011)."}, {"id":"II/0047","type":"II","opinion":"2011-11-17","decision":"2012-01-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","5.1"],"scope":"Modification of the metastatic colorectal cancer indication in combination with FOLFOX4 to an extended combination with FOLFOX but restricted to first line treatment only based on data from the Nordic VII study and additional data on the potential negative dynamic interaction between oxaliplatin (FOLFOX4) and cetuximab in case of KRAS mutation positive tumours and on the potential biological foundation of the apparent relationship between percentage of EGFR positive tumour cells and negative outcome in patients with KRAS mutation positive tumours. Both sets of data are fulfilling an Annex II condition."}, {"id":"II/0044/G","type":"II","opinion":"2011-09-22","decision":"2011-10-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b","C.I.3.a"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC to amend the warning on interstitial lung disease (ILD) and section 4.8 of the SmPC to include ILD and Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TEN) as adverse drug reactions further to request of the CHMP with assessment of the 9th PSUR. The PL was updated accordingly. In addition, section 4.4 of the SmPC was updated to include a warning on eye disorders further to a CHMP request following PhVWP review of keratitis and ulcerative keratitis cases associated with the use of EGFR inhibitors. Finally, the Pharmacovigilance System version number was removed from Annex II."}, {"id":"II/0042","type":"II","opinion":"2011-05-19","decision":"2011-06-23","affects":["SmPC","Annex II"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.1","4.4","4.5","5.1"],"scope":"Update of sections 4.1 and 5.1 of the SmPC to restrict the indication in combination with chemotherapy for the treatment of metastatic colorectal cancer to the combination with irinotecan-based chemotherapy or FOLFOX4 only. The warning on cardiovascular disorders in section 4.4 and the information on KRAS testing in sections 4.4 and 5.1 of the SmPC were amended. Section 4.5 of the SmPC was also updated to include an interaction with XELOX. A condition to the marketing authorisation was included requesting the submission of upcoming results from study NORDIC VII in order to re-assess the benefit-risk balance of this restricted indication."}, {"id":"II/0041","type":"II","opinion":"2011-03-17","decision":"2011-04-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","5.1","5.2"],"scope":"Update of SmPC sections 4.2, 4.4, and 5.2 with information from paediatric PK study. The MAH took the opportunity to update sections 4.6 and 5.1 of the SmPC according to the SmPC guideline (September 2009) and to update the PI according to the latest version of the QRD template (7.3.1, March 2010)."}, {"id":"II/0039","type":"II","opinion":"2010-09-23","decision":"2010-11-05","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the Summary of Product Characteristics (SmPC) with the addition of aseptic meningitis (frequency unknown) following the assessment of PSUR 8 (PSU 028). The Package Leaflet (PL) was updated accordingly. An explanatory statement on the gravity of skin reactions in section 4.8 of the SmPC and subsequently the reference to it in section 4.4 of the SmPC were deleted. Minor editorial changes were also made to the SmPC."}, {"id":"II/0035","type":"II","opinion":"2010-06-24","decision":"2010-07-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","5.1"],"scope":"Update of section 5.1 of the Summary of Product Characteristics (SmPC) with final efficacy data from clinical study in metastatic colorectal cancer NCIC (CA225025) and updated efficacy data from pivotal studies CRYSTAL (EMR 62 202-013) and OPUS (EMR 62 202-047). Update of sections 4.2, 4.4, 4.5 and 4.8 of the SmPC based on the above and other studies of Erbitux combination with chemotherapy primarily with the aim to prevent use of Erbitux in patients with mutant KRAS and to include information regarding cardiovascular events. The PL was updated accordingly."}, {"id":"IB/0038","type":"IB","opinion":"2010-07-28","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"To delete \"do not freeze\" from the product information."}, {"id":"II/0033","type":"II","opinion":"2010-04-22","decision":"2010-06-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance system (DDPS) to version 9.0. Consequently, Annex II has been updated with the new version number of the agreed DDPS. The MAH also took the opportunity to update Annex II with version number 12.0 of the Risk Management Plan, which was agreed following the recent conclusion of the assessment of PSUR 8, and to introduce changes in the SmPC, Labelling and PL pending since the linguistic review following the recent renewal (EMEA/H/C/000558/R/30)."}, {"id":"II/0029","type":"II","opinion":"2009-11-19","decision":"2010-01-20","affects":[],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"R/0030","type":"R","opinion":"2009-04-23","decision":"2009-06-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0028","type":"II","opinion":"2008-10-23","decision":"2008-11-24","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition of an active substance manufacturer."}, {"id":"II/0026","type":"II","opinion":"2008-10-23","decision":"2008-11-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the indication to include treatment of recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN) in combination with platinum-based chemotherapy."}, {"id":"II/0020","type":"II","opinion":"2008-05-30","decision":"2008-07-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"To update the current indication for the use in patients with KRAS wild type metastatic colorectal cancer in combination with chemotherapy and to add a monotherapy indication in KRAS-wild type patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan. The Annex II has been amended to include the latest statement on Risk Management Plan. Editorial amendments have been implemented in the annexes. Furthermore, the package leaflet has been revised following the results of User Testing."}, {"id":"IB/0025","type":"IB","opinion":"2008-05-27","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0022","type":"II","opinion":"2008-01-24","decision":"2008-02-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition of infusion set materials, namely ethyl vinyl acetate bags and polypropylene perfusor syringes, to be used for administration of Erbitux 5 mg/ml."}, {"id":"N/0013","type":"N","opinion":"2007-08-02","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0010","type":"II","opinion":"2007-01-24","decision":"2007-02-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH has applied to update the information on hypomagnesaemia in the SPC sections 4.4 and 4.8, inclusion of \"myocardial infarction, cardiac arrest\" in association with infusion related reactions and replacement of the term \"stenocardia\" with the term \"angina pectoris\" under SPC section 4.8."}, {"id":"X/0009","type":"X","opinion":"2006-12-14","decision":"2007-02-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The Marketing Authorisation Holder applied for the addition of a new formulation at strength of 5 mg/ml cetuximab."}, {"id":"II/0005","type":"II","opinion":"2006-02-23","decision":"2006-03-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Treatment in combination with radiation therapy of patients with locally advanced squamous cell cancer of the head and neck."}, {"id":"II/0004","type":"II","opinion":"2005-07-27","decision":"2005-09-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The product information was updated to include that hypomagnesaemia (loss of a mineral called magnesium in the blood) has been reported with Erbitux."} ] }, "ciltacabtagene-autoleucel__carvykti": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/carvykti-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/carvykti-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000365288","type":"II","opinion":"2026-10-15","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to provide the treating physician the option to determine the setting of the post-infusion monitoring, while maintaining the requirement for monitoring during the period and the proximity to a qualified centre following infusion; the Package Leaflet is updated accordingly. The RMP version 8.3 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI."}, {"id":"PSUSA/00011000/202508","type":"PSUSA","opinion":"2026-03-26","decision":"2026-05-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ciltacabtagene autoleucel"}, {"id":"EMA/VR/0000323641","type":"IA","opinion":"2026-02-10","decision":"2026-05-28","affects":["Annex II"],"codes":["A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release"}, {"id":"EMA/VR/0000294863","type":"IAIN","opinion":"2025-09-04","decision":"2026-05-28","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"To update section 4.4 of the SmPC to implement the signal recommendations on 'Ciltacabtagene autoleucel; idecabtagene vicleucel; tisagenlecleucel – Progressive multifocal leukoencephalopathy (EPITT no 20153)' adopted at the 10 July 2025 PRAC."}, {"id":"EMA/VR/0000285927","type":"IAIN","opinion":"2025-07-11","decision":"2026-05-28","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"EMA/VR/0000272240","type":"II","opinion":"2025-09-18","decision":"2026-05-28","affects":["Annex II","Labelling","PL"],"codes":["A.7","B.II.b.2.b","B.II.b.2.a","B.II.b.2.c.3","B.II.b.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated as follows: To add the manufacturer of the active substance and batch release site. The package leaflet has been updated accordingly."}, {"id":"EMA/VR/0000264446","type":"II","opinion":"2025-07-24","decision":"2026-05-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to amend an existing warning on Secondary malignancies including of T-cell origin to limit the testing only to secondary malignancy of T-cell origin based on the data from clinical studies and literature and to give instruction on monitoring and testing of secondary malignancy of any type in treated patients with HIV."}, {"id":"II/0036","type":"II","opinion":"2025-03-27","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.8, and 5.1 of the SmPC in order to update the list of adverse drug reactions (ADRs), and update clinical efficacy and safety information based on second interim analysis from study 68284528MMY3002 (CARTITUDE-4); this is a phase 3 randomized study comparing ciltacabtagene autoleucel, a chimeric antigen receptor T cell (CAR-T) therapy directed against BCMA, versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in subjects with relapsed and lenalidomide-refractory multiple myeloma; furthermore, the procedure updates section 4.4 and 4.8 of the SmPC to implement safety information regarding secondary malignancy of…"}, {"id":"EMA/N/0000244636","type":"N","opinion":"2025-02-07","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with the addition of the country of destination in section '7. Expiry date and other batch specific information' in the 'Particulars To Appear On The Lot Information Sheet Included With Each Shipment For One Patient'."}, {"id":"II/0027/G","type":"II","opinion":"2024-09-19","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.b","B.II.b.2.a","B.II.b.2.c.3","B.II.b.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II and IIIB have been updated with the following site:"}, {"id":"IAIN/0030","type":"IAIN","opinion":"2024-07-26","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0021","type":"II","opinion":"2024-02-22","decision":"2024-04-19","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least 1 prior therapy, including an IMiD and a PI, have demonstrated disease progression on the last therapy and are refractory to lenalidomide for CARVYKTI, based on interim results from study MMY3002 listed as a specific obligation (SOB/006) in the Annex II. This is an ongoing, Phase 3, randomized, open-label, multicentre study to determine whether treatment with cilta-cel provides an efficacy benefit compared to standard therapy in participants with relapsed and lenalidomide-refractory multiple myeloma."}, {"id":"PSUSA/00011000/202302","type":"PSUSA","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ciltacabtagene autoleucel"}, {"id":"N/0013","type":"N","opinion":"2023-03-09","decision":"2023-12-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0022","type":"IA","opinion":"2023-07-25","decision":"2023-12-07","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0008","type":"R","opinion":"2023-01-26","decision":"2023-03-24","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0004/G","type":"II","opinion":"2022-12-15","decision":"2023-03-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Grouped application comprising two type II variations as follows: - Update of section 4.4 of the SmPC in order to add a new warning on increased risk of severe/fatal COVID-19 infections following Covid-19 signal evaluation from the ongoing study 68284528MMY3002 (CARTITUDE-4) based on a cumulative review of all clinical trials, registries and literature. - Update of section 4.4 of the SmPC in order to add a new warning Risk of severe bleeding in the context of hemophagocytic lymphohistiocytosis syndrome (HLH) following a signal evaluation from the ongoing study 68284528MMY3002 (CARTITUDE-4) based on cumulative review of all clinical trials, registries and literature."}, {"id":"II/0003","type":"II","opinion":"2022-12-15","decision":"2023-03-24","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the existing warnings on cytokine release syndrome (CRS), neurologic toxicities and grading of related events and to update the list of adverse drug reactions (ADRs) based on previously reviewed data from studies MMY2001 and MMY2003, and an additional internal characterisation of neurotoxicity risk; the Package Leaflet is updated accordingly. The RMP version 2.1 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."} ] }, "cobimetinib__cotellic": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/cotellic-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/cotellic-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IG/1730","type":"IG","opinion":"2024-03-26","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0028","type":"II","opinion":"2022-11-24","decision":"2023-04-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0027","type":"II","opinion":"2023-01-12","decision":"2023-04-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to update information based on final results from study ML39302 listed as a category 3 study in the RMP in order to fulfil MEA/003.5; this is a non-interventional PASS study to investigate the effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with and without brain metastasis with BRAF V600 mutant melanoma under real world conditions. The RMP version 5.1 has also been submitted."}, {"id":"II/0025","type":"II","opinion":"2022-05-19","decision":"2023-04-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC based on final results from study GO29665 (iMATRIX_cobimetinib) which corresponds to Study 4 of PIP P/0119/2021. This is a phase I/II, multicentre, open-label, dose-escalation study of the safety, efficacy and pharmacokinetics of cobimetinib in paediatric and young adult patients with previously treated solid tumours. The section 2 of the Package Leaflet is updated accordingly."}, {"id":"N/0024","type":"N","opinion":"2021-11-04","decision":"2022-02-10","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0023","type":"N","opinion":"2021-08-10","decision":"2022-02-10","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0021","type":"IA","opinion":"2021-02-12","decision":"2022-02-10","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0019","type":"R","opinion":"2020-04-30","decision":"2020-06-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0013","type":"N","opinion":"2018-08-09","decision":"2020-06-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0017","type":"IB","opinion":"2019-08-09","decision":"2020-06-25","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"T/0011","type":"T","opinion":"2018-02-20","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00010450/201608","type":"PSUSA","opinion":"2017-03-23","decision":"2017-05-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - cobimetinib"}, {"id":"II/0004/G","type":"II","opinion":"2016-06-23","decision":"2017-05-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.3"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the safety and efficacy results of studies GO28141 and NO25395. The RMP has been updated accordingly (version 2.1). In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor amendments in sections 5.1 and 5.3 of the SmPC."}, {"id":"II/0003","type":"II","opinion":"2016-05-12","decision":"2017-05-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0006/G","type":"IB","opinion":"2016-07-19","decision":"2017-05-24","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.e","B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Change to an approved stability protocol; Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0001/G","type":"II","opinion":"2016-04-28","decision":"2016-06-01","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.2"],"scope":"Update of sections 4.2, 4.8 and 5.2 of the SmPC to reflect the results GP29342 with recommendations for patients with hepatic impairment. Furthermore, the MAH submitted results of the in vitro CYP time-dependent inhibition study (15-1983). In addition, the MAH took the opportunity to use the term CYP3A throughout the SmPC to cover both CYP3A4 and CYP3A5, in line with previous recommendations, and to bring the product in line with the latest QRD template. The Package Leaflet was updated accordingly. The Risk Management Plan was updated to reflect the completion of the studies."}, {"id":"IA/0002","type":"IA","opinion":"2016-01-04","decision":"2016-06-01","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "crizotinib__xalkori": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/xalkori-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/xalkori-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IB/0085/G","type":"IB","opinion":"2024-11-05","decision":"2025-12-18","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IAIN/0086/G","type":"IAIN","opinion":"2024-11-22","decision":"2025-12-18","affects":["Annex II","Labelling"],"codes":["B.II.b.3.a","B.III.1.b.3","B.III.1.b.2","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process; Submission of a new/updated or deletion of Ph. Eur. TSE Certificate of Suitability - Updated certificate from an already approved manufacturer; Submission of a new/updated or deletion of Ph. Eur. TSE Certificate of Suitability - New certificate for a starting material/reagent/intermediate/or excipient from a new or an already approved manufacturer; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"EMA/VR/0000278463","type":"IAIN","opinion":"2025-09-11","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/N/0000246187","type":"N","opinion":"2025-02-25","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representative and deletion of 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4."}, {"id":"X/0080/G","type":"X","opinion":"2024-06-27","decision":"2024-08-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0072","type":"II","opinion":"2022-09-15","decision":"2022-10-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of paediatric patients (age ≥ 6 to < 18 years) with relapsed or refractory systemic anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) and with recurrent, or refractory ALK-positive unresectable inflammatory myofibroblastic tumour (IMT) for Xalkori based on the results from Studies ADVL0912 and A8081013; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. The Annex II was updated to include key elements of the educational material as additional risk minimisation measures. Version 8.2 of the RMP has also been submitted."}, {"id":"PSUSA/00010042/202108","type":"PSUSA","opinion":"2022-04-22","decision":"2022-06-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - crizotinib"}, {"id":"IA/0076","type":"IA","opinion":"2022-02-18","decision":"2022-06-21","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0071","type":"R","opinion":"2021-05-20","decision":"2021-07-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0069","type":"IB","opinion":"2020-10-01","decision":"2021-07-16","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0066","type":"N","opinion":"2019-11-13","decision":"2020-03-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0064","type":"II","opinion":"2019-10-31","decision":"2020-03-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect updated efficacy data from Study A8081001 in patients with ROS1-positive NSCLC. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 10.1."}, {"id":"IB/0061","type":"IB","opinion":"2019-02-28","decision":"2020-03-09","affects":["SmPC","PL"],"codes":["C.I.12"],"outcome":"accepted","kind":"other","sections":[],"scope":"Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring"}, {"id":"II/0055","type":"II","opinion":"2018-09-20","decision":"2018-10-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to provide greater clarity in the crizotinib dose adjustments for patients who receive a reduced dose of crizotinib, either because of pre-existing moderate or severe hepatic impairment or severe renal impairment or because of a previous dose reduction while on treatment with crizotinib. The Package Leaflet has been updated accordingly."}, {"id":"IB/0060/G","type":"IB","opinion":"2018-09-18","decision":"2018-10-23","affects":["SmPC"],"codes":["B.II.d.1.z","B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Other variation; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change to an approved stability protocol"}, {"id":"T/0059","type":"T","opinion":"2018-07-30","decision":"2018-08-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0054","type":"II","opinion":"2018-06-21","decision":"2018-08-31","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to reflect the final analysis of overall survival (OS), a secondary endpoint, in Study A8081014, a randomized phase 3 trial comparing oral crizotinib to first line chemotherapy in patients with ALK-positive advanced non-squamous non-small cell lung cancer (NSCLC)."}, {"id":"II/0051","type":"II","opinion":"2018-01-25","decision":"2018-08-31","affects":["SmPC","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Coadministration of crizotinib with strong CYP3A inhibitors is expected to increase crizotinib plasma concentrations. Coadministration of a single 150 mg oral dose of crizotinib in the presence of ketoconazole (200 mg twice daily), a strong CYP3A inhibitor, resulted in increases in crizotinib systemic exposure, with crizotinib area-under-the-plasma-concentration versus time curve from time zero to infinity (AUCinf) and maximum observed plasma concentration (Cmax) values that were approximately 3.2 fold and 1.4 fold, respectively, those seen when crizotinib was administered alone."}, {"id":"II/0050","type":"II","opinion":"2017-12-14","decision":"2018-01-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.3","4.4","4.8","5.2"],"scope":"Update of sections 4.2, 4.3, 4.4, 4.8 and 5.2 of the SmPC in order to update the information about hepatic impairment based on the results of study A8081012 which evaluated the effect of hepatic impairment on the pharmacokinetics and safety of crizotinib in advanced cancer patients. The package leaflet is updated accordingly. In addition, RMP version 7.4 is being updated."}, {"id":"II/0049/G","type":"II","opinion":"2017-07-06","decision":"2018-01-18","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["4.1"],"scope":"Update of Annex II of the marketing authorisation to remove Therapeutic Management Guide from the Xalkori educational materials based on the submission of the final results of the Non-Interventional Post-Authorisation Safety Study (PASS) A8081049 “A cross-sectional study to evaluate the effectiveness of Xalkori Therapeutic Management Guide among physicians prescribing Xalkori in Europe”. The final results of PASS A8081050 “A cross-sectional study to evaluate the effectiveness of Xalkori Patient Information Brochure among non-small cell lung cancer (NSCLC) patients receiving Xalkori treatment in Europe” was also submitted."}, {"id":"II/0044","type":"II","opinion":"2016-09-15","decision":"2016-11-11","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to provide the results of the final Progression Free Survival (PFS), Objective Response Rate (ORR), Duration of Response (DR) and Overall Survival (OS) analysis in Study A8081007 (SOB001). The data submitted fulfils the specific obligation SOB 001 and the Conditional Marketing Authorisation is switched to a Marketing Authorisation not subject to specific obligations. The Risk Management Plan (v.7.2) is updated accordingly."}, {"id":"II/0039","type":"II","opinion":"2016-07-21","decision":"2016-08-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include treatment of adults with ROS1-positive advanced non-small cell lung cancer (NSCLC) based on the results of Study A8081001 (a multinational, multicenter, open-label, single-arm study of the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of crizotinib in patients with advanced cancer). Consequential changes are proposed to SmPC sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 and the Package Leaflet is proposed to be updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Annex II. An updated RMP version 7.1 was agreed during the procedure."}, {"id":"II/0034","type":"II","opinion":"2016-06-23","decision":"2016-08-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC with information on the effect of crizotinib on renal function, based on the data reviewed in studies A8081001, A8081005, A8081007 and A8081014. The Package Leaflet has been updated accordingly. Furthermore, minor editorial changes have been introduced in the PI."}, {"id":"R/0041","type":"R","opinion":"2016-05-26","decision":"2016-07-29","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0038","type":"II","opinion":"2016-05-26","decision":"2016-07-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC based on the rifampicin DDI substudy report, a study undertaken in order to evaluate the effect of rifampicin (a strong inducer of CYP3A) on multiple-dose PK of crizotinib in advanced cancer patients. The provision of the study report addresses a part of the post-authorisation measure MEA 009. In addition, the MAH took the opportunity to update the contact details of the local representatives in the Czech Republic, Norway and Sweden in the Package Leaflet."}, {"id":"PSUSA/00010042/201508","type":"PSUSA","opinion":"2016-04-01","decision":"2016-05-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - crizotinib"}, {"id":"II/0033","type":"II","opinion":"2015-11-19","decision":"2016-05-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update the SmPC section 5.1 with revised efficacy data based on results from study A8081007."}, {"id":"IB/0036","type":"IB","opinion":"2015-11-10","decision":"2016-05-26","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0024","type":"II","opinion":"2015-10-22","decision":"2015-11-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to add first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) based on the results of the pivotal Study A8081014; a multinational, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of crizotinib to first-line chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) in patients with previously untreated ALK-positive advanced non-squamous NSCLC, as well as updated safety results from Studies A8081001, A8081005 and A8081007. As a result sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC have been updated and the Package Leaflet has been updated accordingly."}, {"id":"PSUSA/00010042/201502","type":"PSUSA","opinion":"2015-09-24","decision":"2015-11-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - crizotinib"}, {"id":"N/0027","type":"N","opinion":"2015-04-08","decision":"2015-07-17","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0022","type":"II","opinion":"2015-01-22","decision":"2015-07-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.2"],"scope":"Update of sections 4.8 and 5.2 of the SmPC to reflect results of an ECG substudy report from Study A8081007 and Study A8081005."}, {"id":"II/0021","type":"II","opinion":"2015-04-23","decision":"2015-07-17","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to include the results of an ophthalmological substudy (A8081001-ophtalmological report) with crizotinib."}, {"id":"II/0016","type":"II","opinion":"2014-07-24","decision":"2015-07-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"R/0015","type":"R","opinion":"2014-06-26","decision":"2014-08-22","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUV/0012","type":"PSUV","opinion":"2014-03-20","decision":"2014-05-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0013","type":"II","opinion":"2014-02-20","decision":"2014-03-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to correct safety margins for systemic toxicities."}, {"id":"II/0004","type":"II","opinion":"2014-02-20","decision":"2014-03-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC in order to reflect updated efficacy and safety data from studies A8081001 and A8081005 and data from the comparative phase III study A8081007 in order to fulfil the obligation to conduct post – authorisation measures and to partially address the conditions imposed to the marketing authorisation. The Annex II and Package Leaflet are updated accordingly."}, {"id":"N/0008","type":"N","opinion":"2013-07-19","decision":"2014-01-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0007","type":"II","opinion":"2013-12-18","decision":"2014-01-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 to propose an adjustment of the dose of crizotinib in patients with severe renal impairment further to the results of study A8081020. The Package Leaflet is updated accordingly."}, {"id":"II/0005/G","type":"II","opinion":"2013-10-24","decision":"2014-01-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC to reflect the results of population modelling analysis plan of the main studies 1001, 1005 and 1007 on special patient groups. Update of sections 4.5 and 5.2 to reflect the outcome of in vitro studies investigating the effect of crizotinib on UGT and as inhibitor of BSEP and renal uptake transporters. Update of sections 4.5 and 5.2 to reflect the outcome of a drug-drug interaction study with proton-pump inhibitors and H2 antagonists. The Package leaflet is updated accordingly. In addition, the MAH took the opportunity of this group of variations to include minor editorial changes."}, {"id":"II/0002","type":"II","opinion":"2013-04-25","decision":"2013-08-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to include the outcome of in vitro studies indicating that crizotinib is an inhibitor of CYP2B6 and may be an inducer of CYP3A4. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. The MAH took also the opportunity of this variation to introduce editorial changes in the SmPC and to correct discrepancies between section 4 of the PL and section 4.8 of the SmPC regarding frequency of rash, and leukopenia. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"IB/0003","type":"IB","opinion":"2013-01-28","decision":"2013-08-26","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"} ] }, "dabrafenib__finlee": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/finlee-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/finlee-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000323418","type":"IA","opinion":"2026-01-21","decision":"2026-03-25","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000308071","type":"IAIN","opinion":"2025-11-03","decision":"2026-03-25","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update Section 4.8 of the SmPC and Section 4 of the PL to implement the signal recommendations on 'Tattoo associated skin reaction (EPITT no 20160)' adopted at the 4 September 2025 PRAC."}, {"id":"EMA/PSUR/0000296502","type":"PSUSA","opinion":"2026-01-29","decision":"2026-03-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment"}, {"id":"PSUSA/00010084/202405","type":"PSUSA","opinion":"2025-01-30","decision":"2025-04-04","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dabrafenib"}, {"id":"IAIN/0011","type":"IAIN","opinion":"2024-12-03","decision":"2025-04-04","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/2762","type":"WS","opinion":"2025-03-20","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC for Spexotras and update of section 5.2 pf the SmPC for Finlee in order to modify administration instructions and pharmacokinetic properties on food effect based on final results from study CDRB436G2102. This is a randomized, open-label, two independent part, 2 x 2 cross-over study to investigate the relative bioavailability of trametinib and dabrafenib liquid formulations under fasted vs. low-fat low-calorie meal conditions in adult healthy participants. In addition, the MAH took the opportunity to implement editorial changes to the PI."}, {"id":"WS/2693","type":"WS","opinion":"2024-07-18","decision":"2025-02-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to add photosensitivity to the list of adverse drug reactions (ADRs) with frequency Common respectively and to update efficacy and safety information on paediatric population based on final results from study CDRB436G2201; this is a phase II open-label global study to evaluate the effect of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive Low Grade Glioma (LGG) or relapsed or refractory High Grade Glioma (HGG). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes."}, {"id":"WS/2671","type":"WS","opinion":"2024-05-16","decision":"2025-02-21","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Atrioventricular (AV) block’ with an uncommon frequency for Finlee and Spexotras and common frequency for Tafinlar to the list of adverse drug reactions (ADRs), following the PRAC recommendation in the PSUR for Mekinist (PSUSA/00010262/202305). The Package Leaflet is updated accordingly."}, {"id":"WS/2670","type":"WS","opinion":"2024-04-11","decision":"2025-02-21","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2612","type":"WS","opinion":"2024-04-25","decision":"2025-02-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Tumour lysis syndrome and add Tumour lysis syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the review of MAH global database, clinical trials database and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and to introduce editorial changes."}, {"id":"IG/1769","type":"IG","opinion":"2024-08-07","decision":"2025-02-21","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2023-12-22","decision":"2025-02-21","affects":["Annex II","PL"],"codes":["A.4","B.II.b.2.c.1","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"} ] }, "dabrafenib__tafinlar": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tafinlar-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tafinlar-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000278305","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of differentiated thyroid cancer (DTC) for Tafinlar and Mekinist based on primary analysis from pivotal study CDRB436J12301. This is a randomized, double-blind, placebo-controlled phase 3 study to evaluate the efficacy and safety of dabrafenib plus trametinib in previously treated patients with locally advanced or metastatic, radio-active iodine refractory BRAF V600E mutation-positive differentiated thyroid cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the Tafinlar SmPC and sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the Mekinist SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000271728","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include treatment of unresectable or metastatic melanoma with a BRAF V600 mutation and adjuvant treatment of Stage III melanoma with a BRAF V600 mutation for adolescents aged 12 years and older for TAFINLAR and MEKINIST, based on an extrapolation report using a modelling and simulation approach to demonstrate PK, PD and efficacy of dabrafenib and trametinib in adolescent patients. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. RMP versions 15.0 and 23.0 for Tafinlar and Mekinist, respectively, have also been submitted."}, {"id":"PSUSA/00010084/202505","type":"PSUSA","opinion":"2026-01-29","decision":"2026-03-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dabrafenib"}, {"id":"EMA/VR/0000308071","type":"IAIN","opinion":"2025-11-03","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update Section 4.8 of the SmPC and Section 4 of the PL to implement the signal recommendations on 'Tattoo associated skin reaction (EPITT no 20160)' adopted at the 4 September 2025 PRAC."}, {"id":"EMA/VR/0000282426","type":"IB","opinion":"2025-07-21","decision":"2026-03-26","affects":["Annex II","PL"],"codes":["A.7","B.I.a.2.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Changes in the manufacturing process of the active substance - Other variation"}, {"id":"WS/2685","type":"WS","opinion":"2024-05-30","decision":"2025-04-04","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"WS/2671","type":"WS","opinion":"2024-05-16","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Atrioventricular (AV) block’ with an uncommon frequency for Finlee and Spexotras and common frequency for Tafinlar to the list of adverse drug reactions (ADRs), following the PRAC recommendation in the PSUR for Mekinist (PSUSA/00010262/202305). The Package Leaflet is updated accordingly."}, {"id":"WS/2647","type":"WS","opinion":"2024-07-25","decision":"2025-04-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8, and 5.1 of the SmPC for Tafinlar and section 5.1 of the SmPC for Mekinist in order to update efficacy and safety information based on final results from study CDRB436F2301 (COMBI-AD); this is a phase 3 randomized double blind study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of high-risk BRAF V600 mutation-positive melanoma after surgical resection. The RMP version 11.1 for Tafinlar and version 19.2 for Mekinist have also been submitted. In addition, MAH took the opportunity to introduce minor editorial changes to the Product Information."}, {"id":"WS/2612","type":"WS","opinion":"2024-04-25","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Tumour lysis syndrome and add Tumour lysis syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the review of MAH global database, clinical trials database and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and to introduce editorial changes."}, {"id":"PSUSA/00010084/202405","type":"PSUSA","opinion":"2025-01-30","decision":"2025-04-04","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dabrafenib"}, {"id":"IG/1769","type":"IG","opinion":"2024-08-07","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"IG/1710","type":"IG","opinion":"2024-03-07","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"IAIN/0075/G","type":"IAIN","opinion":"2024-12-04","decision":"2025-04-04","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0072/G","type":"IAIN","opinion":"2024-06-19","decision":"2025-04-04","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0062/G","type":"IAIN","opinion":"2023-08-16","decision":"2024-02-01","affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0059","type":"IAIN","opinion":"2023-02-24","decision":"2024-02-01","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL to implement the signal recommendations on `Dabrafenib; trametinib – Haemophagocytic lymphohistiocytosis’ (EPITT no: 19824), adopted at the 12 Jan 2023 PRAC meeting."}, {"id":"WS/2114","type":"WS","opinion":"2021-11-11","decision":"2022-10-31","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with the final efficacy data from Study BRF113928 (CDRB436E2201), conducted in patients with stage IV BRAF V600 mutant NSCLC, in fulfilment of a post-authorisation measure (REC) from the initial MA."}, {"id":"WS/2070","type":"WS","opinion":"2021-07-22","decision":"2021-08-26","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.1"],"scope":"Update of sections 4.2, 4.4 and 5.1 of the SmPC in order to update the recommendations for the management of pyrexia and to reflect the results of cross comparison clinical studies that used either the existing or updated pyrexia management guidance; the Package Leaflets are updated accordingly. In addition, the WSA took the opportunity to update the list of local representatives and to include minor editorial changes in the Package Leaflets. The requested worksharing procedure proposed amendments to the Summary of Product Characteristics, and Package Leaflet."}, {"id":"WS/2008/G","type":"WS","opinion":"2021-06-03","decision":"2021-08-26","affects":["SmPC"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 5-years efficacy results from study Phase III study COMBI-AD. This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection in adult patients with a BRAF V600 mutation. Type IA A.6 update of the SmPC with the updated ATC codes released by WHO"}, {"id":"IAIN/0050","type":"IAIN","opinion":"2021-01-11","decision":"2021-08-26","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0047","type":"IAIN","opinion":"2020-12-08","decision":"2021-08-26","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/1636/G","type":"WS","opinion":"2019-11-21","decision":"2020-05-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 5-years overall survival (OS) results from study MEK115306 (COMBI-d), a phase III, randomised, double-blinded study comparing the combination of dabrafenib and trametinib to dabrafenib and placebo in first-line therapy for subjects with unresectable or metastatic BRAF V600/K mutation-positive cutaneous melanoma and the 5-years overall survival (OS) results from study MEK116513 (COMBI-v), a phase III, open-label, 2 arm, randomised study comparing dabrafenib and trametinib combination therapy with vemurafenib monotherapy in BRAF V600 mutation-positive metastatic melanoma."}, {"id":"II/0038","type":"II","opinion":"2019-05-16","decision":"2020-05-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8"],"scope":"Update of section 4.6 of the SmPC in order to update information on fertility, pregnancy and lactation after routine review of the company core data sheet, taking into consideration the original source documentation from GSK (former MAH), current scientific knowledge, published literature, as well as health authority and working group guidelines. The Package leaflet is being updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to include some editorial changes in section 4.4 and 4.8 of the SmPC and in section 4 of the package leaflet."}, {"id":"WS/1468","type":"WS","opinion":"2019-02-14","decision":"2019-05-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to reflect study results from study BRF117277, a Phase II, Open-Label, Multicentre Study of Dabrafenib plus Trametinib in Subjects with BRAF Mutation- Positive Melanoma that has Metastasized to the Brain (COMBI-MB)."}, {"id":"IB/0039/G","type":"IB","opinion":"2019-02-20","decision":"2019-05-27","affects":["SmPC","Labelling","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.1.e","B.II.b.2.a","B.II.b.3.a","B.II.b.3.z","B.II.c.1.a","B.II.e.1.a.1","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process."}, {"id":"WS/1274","type":"WS","opinion":"2018-07-26","decision":"2018-08-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","5.1"],"scope":"Extension of indication to include the combination adjuvant treatment with trametinib and dabrafenib of adult patients with stage III melanoma with a BRAF V600 mutation, following complete resection. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 of the Mekinist and Tafinlar SmPCs are updated. The Package Leaflet and the Risk Management plan (version 14.1 for Mekinist and version 9.1 for Tafinlar, according to GVP module V revision 2) are updated in accordance."}, {"id":"T/0032","type":"T","opinion":"2018-06-01","decision":"2018-07-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"WS/1210/G","type":"WS","opinion":"2018-01-25","decision":"2018-05-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1","6.4"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 3-years overall survival (OS) results from study MEK115306 (COMBI-d), a phase III, randomised, double-blinded study comparing the combination of dabrafenib and trametinib to dabrafenib and placebo in first-line therapy for subjects with unresectable or metastatic BRAF V600/K mutation-positive cutaneous melanoma."}, {"id":"R/0030","type":"R","opinion":"2018-02-22","decision":"2018-05-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0029","type":"II","opinion":"2018-01-18","decision":"2018-05-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to update the information on the in vitro evaluation of drug-drug interaction potential (to include that dabrafenib is a human BCRP substrate and a OCT2 inhibitor but that the risk of a drug drug interaction is minimal with substrates of OAT1, OAT3 and OTC2 based on clinical exposure of dabrafenib and its metabolites), based on the results of non-clinical studies 2014N220059 and 2015N235499."}, {"id":"II/0025","type":"II","opinion":"2017-10-05","decision":"2018-05-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4, 4.5 and 5.2 of the SmPC to include the results of a drug-drug interaction between dabrafenib and rosuvastatin (an OATP1B1/1B3 substrate) and between dabrafenib and midazolam (a CYP3A4 substrate) based on study 200919; this is a phase I open-label fixed sequence study to evaluate the effects of an OATP1B1/1B3 substrate (rosuvastatin) and of a CYP3A4 substrate (midazolam) on the repeat dose pharmacokinetics of dabrafenib in subjects with BRAFV60 mutation positive tumours, in fulfillment of MEA 001."}, {"id":"II/0024","type":"II","opinion":"2017-07-06","decision":"2018-05-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to include the results of a drug-drug interaction between dabrafenib and rifampicin (a CYP3A4/CYP2C8 inducer) and between dabrafenib and rabeprazole based on the final results of study 200072, a phase I open-label fixed sequence study to evaluate the effects of potent CYP3A4 inducer (rifampicin) and of a pH elevating agent (rabeprazole) on the repeat dose pharmacokinetics of dabrafenib in subjects with BRAFV60 mutation positive tumours, to fulfil MEA 005."}, {"id":"PSUSA/00010084/201608","type":"PSUSA","opinion":"2017-03-23","decision":"2017-05-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dabrafenib"}, {"id":"WS/0996","type":"WS","opinion":"2017-02-23","decision":"2017-03-29","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include the combination treatment with trametinib and dabrafenib of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600 mutation. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the Mekinist and Tafinlar SmPC are updated. The Package Leaflet and RMP are updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to align the SmPCs of Mekinist and Tafinlar. Furthermore, the Product Information is brought in line with the latest QRD template version 10."}, {"id":"II/0019","type":"II","opinion":"2016-05-12","decision":"2017-03-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of SmPC sections 4.2, 4.4, 4.8 and 5.1 based on the final study report from Study BRF113773, which was undertaken to assess the QTcF interval prolongation potential of dabrafenib in order to fulfil the post-approval measure (PAM) MEA 002."}, {"id":"II/0018","type":"II","opinion":"2016-04-01","decision":"2016-05-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of section 4.8 of the SmPC for the inclusion of “Bradycardia” and “Heart rate decreased” to reflect the known safety profile of dabrafenib when used in combination with trametinib. Additionally, the acronyms ‘BID’ and ‘QD’ have been replaced with ‘twice daily’ and ‘once daily’, respectively and section 4.2 of the SmPC has also been updated for the third recommended dose reduction. The Package Leaflet is updated in accordance. Furthermore, the PI is brought in line with the QRD template version 9.1."}, {"id":"II/0015/G","type":"II","opinion":"2015-10-08","decision":"2016-05-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update preclinical safety data on juvenile toxicity in rats and phototoxicity in mouse on the basis of submitted non clinical studies."}, {"id":"II/0009","type":"II","opinion":"2015-09-24","decision":"2016-05-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to reclassify the already listed ADR panniculitis from an immune disorder to a skin and subcutaneous tissue disorder."}, {"id":"WS/0736","type":"WS","opinion":"2015-07-23","decision":"2015-08-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","5.1","5.3"],"scope":"Extension of indication to add a new therapeutic indication for the use in combination of trametinib and dabrafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 5.1, 5.3 of the SmPC are updated. The Package Leaflet was updated accordingly. Furthermore, an updated RMP version X was approved as part of the application."}, {"id":"II/0008","type":"II","opinion":"2015-06-11","decision":"2015-08-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0014/G","type":"IAIN","opinion":"2015-07-13","decision":"2015-08-25","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0010","type":"T","opinion":"2015-04-13","decision":"2015-05-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation Transfer from GlaxoSmithKline Trading Services to Novartis Europharm Limited. Transfer of Marketing Authorisation"}, {"id":"II/0006","type":"II","opinion":"2015-01-22","decision":"2015-05-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on data from the non-clinical study 13DMM028 provided to fulfil MEA006 (drug-drug interaction in vitro organic anion transporter polypeptide substrate assay)."}, {"id":"PSUV/0005","type":"PSUV","opinion":"2014-09-25","decision":"2014-11-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0002/G","type":"II","opinion":"2014-02-20","decision":"2014-11-21","affects":["SmPC","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 with new data from a 26-week toxicology study in mice (G12071). In addition, the MAH revised the submission date for the final report for a drug-drug interaction study (MEA 006) and has updated the RMP accordingly. The MAH also took the opportunity to update the list of local representatives."}, {"id":"II/0001/G","type":"II","opinion":"2014-07-24","decision":"2014-11-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IG/0442","type":"IG","opinion":"2014-06-05","decision":"2014-11-21","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"} ] }, "dacomitinib__vizimpro": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vizimpro-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IAIN/0012","type":"IAIN","opinion":"2024-12-11","decision":"2025-11-21","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"R/0011","type":"R","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IA/0007","type":"IA","opinion":"2021-07-02","decision":"2022-06-29","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0004","type":"N","opinion":"2020-11-27","decision":"2021-01-22","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0003/G","type":"II","opinion":"2020-12-10","decision":"2021-01-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to revise the dosing recommendation for patients with hepatic impairment and include relevant pharmacokinetics data based on results of Study A7471058, evaluating the effect of severe hepatic impairment on the plasma PK, safety and tolerability after a single dose of dacomitinib. As a consequence, the MAH is proposing to remove the missing information “Safety in Patient with Severe Hepatic Impairment” from the list of safety concerns in the RMP v2.0. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1."} ] }, "daratumumab__darzalex": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/darzalex-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/darzalex-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000334930","type":"II","opinion":"2026-06-11","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ''Hypotension and Weigt decreased'' to the list of adverse drug reactions (ADRs) with frequency ''Common'' and to update the description of the Summary of the safety profile to remove influenza of the serious adverse reactions based on final results from study AMY2009 listed as a category 3 study in the RMP; this is phase 2, a multicenter, prospective study of daratumumab-based therapy in newly diagnosed patients with Amyloid light-chain (AL) amyloidosis and with pre-existing Mayo Cardiac Stage II and IIIa cardiac involvement, to further characterize cardiac adverse effects in terms of incidence, severity, clinical presentation, management,…"}, {"id":"EMA/VR/0000312940","type":"II","opinion":"2026-03-26","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to introduce, upon physician’s discretion, the possibility of self-administration of Darzalex SC by patients or their caregivers, based on results from four human factor studies. The Package Leaflet is updated accordingly. In addition, the Labelling section is updated to include information in Braille."}, {"id":"EMA/VR/0000313969","type":"II","opinion":"2026-02-05","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a warning on ‘Infections’. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000282640","type":"II","opinion":"2025-11-27","decision":null,"affects":["Annex II","PL"],"codes":["B.II.c.2.a","B.II.c.2.d","B.II.c.4.c","B.I.b.2.e","B.II.e.1.z","B.II.b.1.a","B.II.b.2.c.1","B.II.b.2.b","B.II.b.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated as follows: Section A MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURE RESPONSIBLE FOR BATCH RELEASE is being updated to include: Janssen Pharmaceutica NV Turnhoutseweg 30 2340 Beerse Belgium Under the ‘Name and address of the manufacturer responsible for batch release’ The Package Leaflet have been updated accordingly."}, {"id":"EMA/VR/0000284866","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"Update of sections 4.2 and 6.6 of the SmPC for the subcutaneous formulation in order to improve guidance for minimizing the risk for stopper coring. In addition, the MAH took the opportunity to introduce editorial and administrative changes to the PI, including to the Annex II, Labelling and the Package Leaflet. The list of local representatives in the Package Leaflet has also been updated."}, {"id":"EMA/VR/0000290174","type":"IAIN","opinion":"2025-08-04","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Secondary packaging site; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0077","type":"II","opinion":"2025-06-19","decision":"2025-07-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"EMA/VR/0000263940","type":"II","opinion":"2025-06-12","decision":"2025-07-18","affects":["Annex II","PL"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated as follows: Addition of Samsung Biologics Co, Ltd., Plant 3, 300, Songdo bio-daero, Yeonsu-gu, Incheon, Republic of Korea as additional manufacturer of the biological active substance. The package leaflet has been updated as follows: Editorial correction to the local representatives for Iceland."}, {"id":"EMA/VR/0000254725","type":"II","opinion":"2025-05-08","decision":"2025-07-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study AMY3001 listed as PAES in the Annex II; this is a randomized phase 3 study to evaluate the efficacy and safety of daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD in newly diagnosed systemic AL amyloidosis."}, {"id":"II/0076","type":"II","opinion":"2025-02-27","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for Darzalex in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma and who are ineligible for stem cell transplant (SCT), based on the results from Study CEPHEUS (54767414MMY3019), a randomised, open-label, active-controlled, multi-centre phase 3 study. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 11.1 of the RMP has also been submitted. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0074","type":"II","opinion":"2024-09-19","decision":"2024-10-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the results from the final (overall survival) analysis from study 54767414MMY3008 (MAIA). This is a Phase 3 randomized, open-label, parallel-group, active controlled, multicenter study comparing daratumumab, lenalidomide, and dexamethasone (DRd) vs lenalidomide and dexamethasone (Rd) in subjects with previously untreated multiple myeloma who are ineligible for high dose therapy. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0072","type":"II","opinion":"2024-09-19","decision":"2024-10-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include Darzalex as a subcutaneous injection in combination with bortezomib, lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma, who are eligible for autologous stem cell transplant, based on the primary analysis results from the pivotal study 54767414 / MMY3014 (PERSEUS), a randomised, open-label, active-controlled, multicentre phase 3 study. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 10.1 of the RMP has also been submitted."}, {"id":"II/0070","type":"II","opinion":"2024-02-15","decision":"2024-10-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on the final overall survival analysis results from study MMY3007. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce minor editorial changes."}, {"id":"IB/0071/G","type":"IB","opinion":"2024-02-20","decision":"2024-10-21","affects":["SmPC"],"codes":["B.I.d.1.z","B.II.f.z","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period or storage conditions - Other variation; Stability of FP - Other variation; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0064","type":"II","opinion":"2023-02-09","decision":"2024-01-25","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC following submission of the final report from study MMY3013 (54767414MMY3013). This is a Phase III, randomized, open-label study comparing daratumumab, pomalidomide and low-dose dexamethasone (DaraPomDex) with pomalidomide and low-dose dexamethasone (PomDex) in subjects with relapsed or refractory multiple myeloma who have received at least 1 prior treatment regimen with both lenalidomide and a proteasome inhibitor and have demonstrated disease progression."}, {"id":"II/0063","type":"II","opinion":"2023-02-09","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","6.3"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the warnings and precautions for ocular events following PSUSA/00010498/202111, based on the cumulative review of the relevant cases retrieved from the MAH’s global safety database, clinical database, epidemiological evaluation and literature review. In addition, the MAH took the opportunity for a minor correction in section 6.3 SmPC."}, {"id":"IB/0069/G","type":"IB","opinion":"2023-11-14","decision":"2024-01-25","affects":["SmPC"],"codes":["B.II.f.z","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Other variation; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0062","type":"II","opinion":"2022-11-24","decision":"2023-01-10","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add COVID-19 to the list of adverse drug reactions (ADRs) with frequency common, based on a pooled dataset from the following interventional studies 4767414MMY2004, 54767414MMY3003, 54767414MMY3006, 54767414MMY3008, and 54767414MMY3013. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0060/G","type":"II","opinion":"2022-06-02","decision":"2023-01-10","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of SmPC to include the final overall survival (OS) results based on the final OS analysis for pivotal study 54767414MMY3003 (MMY3003). MMY3003 (Pollux) is an open-label, randomized, active-controlled Phase III study that compared treatment with DARZALEX 16mg/kg in combination with lenalidomide and low-dose dexamethasone (DRd) to treatment with lenalidomide and low-dose dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma who had received at least one prior therapy. C.I.4: Update of section 5.1 of SmPC to include the final overall survival (OS) results based on the final OS analysis for pivotal Studies 54767414MMY3004 (MMY3004)."}, {"id":"II/0059/G","type":"II","opinion":"2022-05-12","decision":"2023-01-10","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.b.2.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated as follows: Addition of Janssen Sciences Ireland UC, Barnahely, Ringaskiddy, Cork, Ireland as manufacturer of a biological active substance."}, {"id":"II/0056/G","type":"II","opinion":"2022-01-20","decision":"2023-01-10","affects":["SmPC","Annex II"],"codes":["B.I.a.2.c","B.II.f.1.b.5","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - The change refers to a [-] substance in the manufacture of a biological/immunological substance which may have a significant impact on the medicinal product and is not related to a protocol; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"II/0053","type":"II","opinion":"2022-02-24","decision":"2023-01-10","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update PFS and OS) data based on interim results from study MMY3008; This is a Phase 3, randomized, open-label, active controlled, parallel-group, multicenter study in adults with newly diagnosed MM not eligible for ASCT comparing DRd vs Rd. The Marketing authorisation holder (MAH) took the opportunity to make minor formatting and linguistic changes in the PI. is recommended for approval. Amendments to the marketing authorisation In view of the data submitted with the variation, amendments to Annex(es) I are recommended."}, {"id":"IB/0061/G","type":"IB","opinion":"2022-06-30","decision":"2023-01-10","affects":["SmPC"],"codes":["A.6","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0057","type":"IB","opinion":"2022-02-26","decision":"2023-01-10","affects":["SmPC","PL"],"codes":["B.II.f.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After first opening (supported by real time data)"}, {"id":"R/0054","type":"R","opinion":"2021-11-11","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0051/G","type":"II","opinion":"2021-10-07","decision":"2022-01-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update PFS data based on interim results from study MMY3006 (CCO 27/8/2020); this is a Phase 3, randomized, open-label, parallel-group, active-control, multi-center study of daratumumab combined with VTd for NDMM patients eligible for ASCT. This fulfils a post-approval commitment of procedure EMEA/H/C/004077//II/0030 to provide updated Part 1 PFS data, with censoring the patients randomized to daratumumab in Part 2 of this study."}, {"id":"II/0050","type":"II","opinion":"2021-10-07","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add hypogammaglobulinemia to the list of adverse drug reactions (ADRs) with frequency common, based on new information and previously reviewed pooled safety data from Part 2 of Phase 3 Clinical Study 54767414MMY3006 comparing daratumumab versus observation as maintenance in patients with newly diagnosed Multiple Myeloma who are post-ASCT transplant. The Package Leaflet is updated accordingly."}, {"id":"II/0049/G","type":"II","opinion":"2021-07-22","decision":"2022-01-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.3.c","B.II.a.3.b.3","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished or intermediate product - The product is a biological/immunological medicinal product and the change requires an assessment of comparability; Changes in the composition (excipients) of the finished product - Other excipients - Change that relates to a biological/immunological product; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0047","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC in order to to include a fatal outcome for IRRs following a systematic cross-programmatic review of fatal cases of Infusion Related Reaction (IRR) with use of daratumumab. In addition, the MAH has taken the opportunity to correct in section 4.8 the reported incidence rate of Grade 3 or 4 treatment-emergent infections from Study MMY3003 for DRd from 27% to 28%. In addition, the marketing authorisation holder has taken the opportunity to update the list of local representatives in the PL and implement minor editorial changes in SmPC, Labelling and PL. is recommended for approval."}, {"id":"II/0044","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication for Darzalex subcutaneous formulation to include combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide-refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or after the last therapy; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. In addition, section 4.8 of the SmPC for the intravenous formulation is also updated based on the pooled safety analysis."}, {"id":"II/0043","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include treatment of adult patients with newly diagnosed systemic light chain (AL) amyloidosis in combination with cyclophosphamide, bortezomib and dexamethasone; The variation leads to amendments to the Summary of Product Characteristics, Annex II, Package Leaflet and to the Risk Management Plan (RMP). Amendments to the marketing authorisation In view of the data submitted with the variation, amendments to Annex(es) I, II and IIIB and to the Risk Management Plan are recommended. Similarity with authorised orphan medicinal products Not applicable."}, {"id":"II/0041","type":"II","opinion":"2020-12-03","decision":"2021-06-21","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include CMV infections as a new adverse drug reaction (ADR) with frequency common following a comprehensive, cross-program evaluation of all potential cases of treatment-emergent cytomegalovirus (CMV) infections with use of daratumumab. The Package Leaflet is updated accordingly. Several minor linguistic improvements are also proposed."}, {"id":"II/0039","type":"II","opinion":"2020-06-11","decision":"2021-06-21","affects":["SmPC"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update information regarding immunogenicity following completion of post-authorization commitments regarding re-analysis of all ADA samples taken from previously submitted clinical using the Enhanced DT Method (previously developed as a result of PAM-MEA-005). The Important Potential Risk of immunogenicity is removed from the RMP and version 6.5 is submitted"}, {"id":"II/0038","type":"II","opinion":"2020-07-09","decision":"2021-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update section 4.8 of the SmPC in order to add sepsis with frequency common as an ADR and incidence data on fatal infections and adverse reactions in the elderly patients based on cross-programmatic review of data. The MAH also proposed minor corrections in section 4.8 of the SPC. The Package Leaflet and labelling is updated accordingly. Correction of Annex II to add the active substance manufacturer “Samsung Biologics, Korea”, which was overlooked during procedure II-018 (approved on 11 July 2019)"}, {"id":"X/0032","type":"X","opinion":"2020-04-30","decision":"2020-06-03","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration"}, {"id":"II/0035","type":"II","opinion":"2020-03-26","decision":"2020-06-03","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on interim results from phase III follow up studies of 3 approved combination treatments of daratumab (D) in relapsed or refractory MM patients MMY3003 (DRd vs Rd) and MMY3004 (DVd vs Vd) and in newly diagnosed MM patients MMY3007 (DVd vs Vd). In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce some minor editorial changes in the PI and to update the list of local representatives for Italy in the Package Leaflet."}, {"id":"II/0030","type":"II","opinion":"2019-12-12","decision":"2020-01-20","affects":["SmPC","Labelling"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1"],"scope":"Extension of indication in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT) for Darzalex; as a consequence, sections 4.1, 4.2, 4.5, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP (version 6.4) has also been agreed."}, {"id":"II/0029","type":"II","opinion":"2019-10-17","decision":"2019-11-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1","5.2"],"scope":"Extension of indication in combination with lenalidomide and dexamethasone (Rd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) for Darzalex; as a consequence, sections 4.1, 4.2, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP has been updated accordingly (finally agreed version 6.2). Furthermore, the Annex II is brought in line with the latest QRD template version 10.1."}, {"id":"II/0027","type":"II","opinion":"2019-05-29","decision":"2019-06-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to introduce a new warning and to add the recently identified risk of Hepatitis B reactivation as an uncommon adverse drug reaction, respectively. The PL and the RMP (v. 5.0 rev2) are amended accordingly. A DHPC to inform prescribers on the newly identified risk has been agreed."}, {"id":"IB/0022","type":"IB","opinion":"2018-11-30","decision":"2019-06-28","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"N/0024","type":"N","opinion":"2018-10-12","decision":"2018-12-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0019","type":"II","opinion":"2018-11-15","decision":"2018-12-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.2"],"scope":"Update of sections 4.2, 4.8 and 5.2 of the SmPC in order to include the possibility for a split first dose for the treatment of patients with multiple myeloma, based on the Phase 1b open-label, non-randomised, multicentre Study 54767414MMY1001. The package leaflet is updated accordingly."}, {"id":"II/0013","type":"II","opinion":"2018-05-03","decision":"2018-08-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the Darzalex SmPC in order to add anaphylactic reactions with a frequency ‘rare’ as new adverse reactions and update of section 4.4 to complement the existing warning on infusion related reactions based on the cumulative review of clinical trial and post-marketing data. The Package Leaflet (PL) is updated accordingly."}, {"id":"II/0011","type":"II","opinion":"2018-07-26","decision":"2018-08-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of Indication to include the combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant for Darzalex; as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP is updated to version 3.2 (in version 2 of the RMP template). In addition, the Marketing authorisation holder took the opportunity to update Annex II with regards to PSUR requirements and to update the contact details of the Lithuanian and Slovenian local representatives in the Package Leaflet."}, {"id":"II/0014","type":"II","opinion":"2018-03-15","decision":"2018-06-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to add information relating to the daratumumab interference with Serum Protein Electrophoresis (SPE) and Immunofixation (IFE) assays and the daratumumab-specific immunofixation reflex assay (DIRA)."}, {"id":"IB/0008/G","type":"IB","opinion":"2017-08-02","decision":"2018-06-25","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.I.d.1.c","B.II.f.1.b.5","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of AS - Change in the re-test period/storage period or storage conditions - Change to an approved stability protocol; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Stability of FP - Change to an approved stability protocol"}, {"id":"IA/0007/G","type":"IA","opinion":"2017-06-16","decision":"2018-06-25","affects":["Annex II"],"codes":["A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"II/0002","type":"II","opinion":"2017-02-23","decision":"2017-04-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","5.1","5.2"],"scope":"Extension of Indication for Darzalex in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 5.1 and 5.2 of the SmPC are updated in order to update the information on the target patient population, posology, warnings, interactions, efficacy and pharmacokinetics. A new warning is introduced in section 4.4 regarding neutropenia/thrombocytopenia induced by background therapy."} ] }, "darolutamide__nubeqa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/nubeqa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/nubeqa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/nubeqa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf-0"], "procedures": [ {"id":"II/0024","type":"II","opinion":"2025-06-19","decision":"2025-07-17","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include in combination with androgen deprivation therapy (ADT) the treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) for NUBEQA, based on final results from study 21140 (ARANOTE); this is a randomized, double-blind, placebo-controlled Phase 3 study of darolutamide to demonstrate the superiority of darolutamide in addition to ADT over placebo plus ADT in patients with mHSPC. As a consequence, sections 4.1, 4.2, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 5.1 of the RMP has also been submitted."}, {"id":"R/0021","type":"R","opinion":"2024-09-19","decision":"2024-10-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0022","type":"N","opinion":"2024-07-30","decision":"2024-10-24","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00010843/202307","type":"PSUSA","opinion":"2024-03-21","decision":"2024-05-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - darolutamide"}, {"id":"N/0008","type":"N","opinion":"2021-12-09","decision":"2023-02-27","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0012","type":"II","opinion":"2023-01-12","decision":"2023-02-27","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC based on the final report of carcinogenicity study T104877-7 listed as a category 3 study in the RMP. This is a non-clinical study to assess the carcinogenic potential in mice. The study evaluates the effects of daily oral administration of darolutamide for a period of 6 months in tg-rasH2 transgenic mouse model. The updated RMP version 3.2 is approved."}, {"id":"II/0009","type":"II","opinion":"2023-01-26","decision":"2023-02-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel and androgen deprivation therapy, based on final results from Study 17777 (ARASENS); this is a randomized, double-blind, placebo-controlled Phase 3 study designed to demonstrate the superiority of darolutamide in combination with docetaxel over placebo in combination with docetaxel in OS in patients with mHSPC. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC have been updated. The Package Leaflet is updated in accordance. Version 4.1 of the RMP has also been submitted."}, {"id":"II/0002","type":"II","opinion":"2020-10-08","decision":"2021-04-21","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on the final CSR from study 17772 (ARAMIS) listed as a PAES in the Annex II; this is a multinational, randomised, double-blind, placebo-controlled, phase III efficacy and safety study of darolutamide in men with high-risk non-metastatic castration-resistant prostate cancer; the Annex II is updated accordingly. The RMP version 1.1 is accepted."}, {"id":"IB/0001","type":"IB","opinion":"2020-05-12","decision":"2021-04-21","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "dasatinib__dasatinib-accord-healthcare": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/dasatinib-accord-healthcare-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [] }, "dasatinib-anhydrous-__sprycel": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/sprycel-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/sprycel-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000356665","type":"II","opinion":"2026-09-03","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to remove the wording referring to the absence of pleural effusion and pulmonary arterial hypertension in paediatric patients following the update in Company Core Data Sheet and based on results from study CA180226; this is an open label, multi-center, Phase 2 study of dasatinib therapy in children and adolescents with newly diagnosed CP-CML or with Ph+ leukaemias resistant or intolerant to imatinib. The RMP version 19.0 has also been submitted."}, {"id":"EMA/VR/0000320681","type":"IB","opinion":"2026-02-24","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To add a list of local representatives to the PL and update the EMA website address in Section 10 of the SmPC and Section 6 of the PL, in accordance with the QRD template. In addition, the MAH took the opportunity to implement corrections to the translated Product Information (HR, DE, FI, SK, SL, CS, NL, RO, IT, NO)."}, {"id":"EMA/VR/0000254764","type":"IB","opinion":"2025-05-14","decision":"2026-04-30","affects":["SmPC"],"codes":["B.II.e.2.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the immediate packaging of the finished product - Other changes"}, {"id":"IAIN/0092/G","type":"IAIN","opinion":"2024-04-19","decision":null,"affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.a","B.II.b.1.b","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site"}, {"id":"IB/0086","type":"IB","opinion":"2022-06-16","decision":"2023-02-27","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"IAIN/0085","type":"IAIN","opinion":"2022-03-15","decision":"2023-02-27","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"IAIN/0084","type":"IAIN","opinion":"2022-03-14","decision":"2023-02-27","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"PSUSA/00000935/202106","type":"PSUSA","opinion":"2022-01-27","decision":"2022-03-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dasatinib"}, {"id":"IB/0079","type":"IB","opinion":"2021-06-10","decision":"2022-03-22","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IA/0078","type":"IA","opinion":"2021-04-20","decision":"2022-03-22","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IG/1223/G","type":"IG","opinion":"2020-04-17","decision":"2021-04-30","affects":["Annex II","PL"],"codes":["A.5.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IB/0076","type":"IB","opinion":"2021-02-25","decision":"2021-04-30","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"II/0064","type":"II","opinion":"2019-06-27","decision":"2020-02-13","affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on results from existing and new pharmacokinetics (PK) analyses together with a review of literature data on the dasatinib PK profile in fasted conditions to assess implications arising for the recommendation for administration, as requested by the CHMP. In addition, the local representative’s details for Germany have been updated. Minor editorial changes have been introduced throughout the Product Information."}, {"id":"IG/1059","type":"IG","opinion":"2019-02-15","decision":"2020-02-13","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUSA/00000935/201806","type":"PSUSA","opinion":"2019-01-31","decision":"2019-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dasatinib"}, {"id":"II/0059","type":"II","opinion":"2018-12-13","decision":"2019-02-06","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include a paediatric indication for Philadelphia chromosome positive acute lymphoblastic leukaemia for Sprycel; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor editorial changes to the product information. The RMP version 16.1 has also been submitted."}, {"id":"IAIN/0061","type":"IAIN","opinion":"2018-08-03","decision":"2019-02-06","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"X/0056/G","type":"X","opinion":"2018-04-26","decision":"2018-07-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"II/0055","type":"II","opinion":"2017-06-09","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add nephrotic syndrome as an adverse reaction based on the results of routine pharmacovigilance activities. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the date of latest renewal (Section 9, SmPC) along with the phone number of the local representative in Croatia and the name of local representative in Ireland listed in the PIL."}, {"id":"R/0050","type":"R","opinion":"2016-05-26","decision":"2016-07-15","affects":["SmPC","Annex II","Labelling"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0049","type":"N","opinion":"2015-10-23","decision":"2016-07-15","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0051","type":"IAIN","opinion":"2016-04-19","decision":"2016-07-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUV/0041","type":"PSUV","opinion":"2015-01-22","decision":"2015-03-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0043/G","type":"II","opinion":"2014-11-20","decision":"2015-03-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0037","type":"II","opinion":"2013-11-21","decision":"2014-08-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC to reflect the potential risk to the foetus when administered during pregnancy, further to a review of data on all pregnancies. Consequently, the RMP was updated accordingly. The contact details of the Dutch representative in the package leaflet have been updated."}, {"id":"II/0036","type":"II","opinion":"2013-07-25","decision":"2014-08-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC with 48-month follow-up data from study CA180056 in patients with newly diagnosed CML in the chronic phase (FU2 027.2). The package leaflet is updated accordingly. Furthermore, Annex II is also updated further to the re-classification of this post-authorisation commitment as a condition to the Marketing Authorisation. The product information is also updated in line with the QRD template version 9.0 and the list of local representatives in the Package leaflet has been updated."}, {"id":"II/0033","type":"II","opinion":"2012-10-18","decision":"2012-11-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC with results from a new statistical evaluation of the tumour data of the 2-year carcinogenicity study in rats."}, {"id":"II/0032","type":"II","opinion":"2012-07-19","decision":"2012-08-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC with 36-month follow-up data from study CA180056 in patients with newly diagnosed CML in the chronic phase (FU2 027.1). The package leaflet is updated accordingly."}, {"id":"II/0031","type":"II","opinion":"2012-01-19","decision":"2012-02-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC further to the results of 5 years of follow-up of the dose optimisation study CA180034. The Package Leaflet has been updated accordingly and also to bring it in line with the SmPC with regards to adverse reactions with a frequency “uncommon” and “rare”."}, {"id":"II/0030","type":"II","opinion":"2011-12-15","decision":"2012-01-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC with 24-month data of study CA180056 in patients with newly diagnosed CML in the chronic phase, further to the request of the CHMP following the assessment of FUM 027. Furthermore, the MAH proposed this opportunity to bring the PI in line with the latest QRD template version 8.1."}, {"id":"R/0028","type":"R","opinion":"2011-07-21","decision":"2011-09-29","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0029","type":"IB","opinion":"2011-06-19","decision":null,"affects":["SmPC"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"The MAH applied to update section 5.3 of the SmPC as requested by the CHMP further to the assessment of the results of a carcinocenicity study in rats (FUM 005). In addition, typographical errors were corrected in the German and Spanish annexes."}, {"id":"IA/0026/G","type":"IA","opinion":"2011-03-11","decision":null,"affects":["Annex II","PL"],"codes":["C.I.9.e","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Changes in the major contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations and described in the DD; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0023","type":"II","opinion":"2010-10-21","decision":"2010-12-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication of Sprycel in the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase. Consequently, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the Summary of Product Characteristics and the Package Leaflet have been updated. Annex II has been updated to include the revised version number of the risk management plan (version 8.1). The MAH also took the opportunity to include the marketing authorisation numbers of recently approved 80 mg and 140 mg strengths in Annexes I and IIIA."}, {"id":"II/0024","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of SmPC section 4.5 with results from the final clinical study report CA180249 on the effect of omeprazole on the pharmacokinetics of dasatinib in healthy subjects."}, {"id":"X/0022","type":"X","opinion":"2010-07-22","decision":"2010-09-30","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Additional strengths of 80 mg and 140 mg film-coated tablets."}, {"id":"IA/0025","type":"IA","opinion":"2010-08-16","decision":null,"affects":["Annex II"],"codes":["C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"II/0020","type":"II","opinion":"2010-02-18","decision":"2010-05-05","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SPC) and section 4 of the Package Leaflet further to a review of safety data from post-marketing experience and from 36-month follow-up safety data from long-term clinical studies. Section 5.1 of the SPC is also updated further to long-term follow-up study data. The Marketing Authorisation Holder also took the opportunity to make minor editorial and linguistic corrections to the SPC and to update the list of local representatives in the Package Leaflet."}, {"id":"IA/0021/G","type":"IA","opinion":"2010-03-10","decision":null,"affects":["Annex II"],"codes":["C.I.9.b","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the contact details of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"IB/0019","type":"IB","opinion":"2010-01-20","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"To change the shelf life of the finished product as packaged for sale."}, {"id":"II/0017","type":"II","opinion":"2009-06-25","decision":"2009-07-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"This type II variation concerns an update of sections 4.2, 4.4 and 5.2 of the SPC, upon request by the CHMP following the assessment of FUM 007, with information concerning patients with hepatic impairment and the results of the pharmacokinetic Study CA189951. In addition, the MAH took the opportunity to update the contact details for Estonia in the list of local representatives in the Package Leaflet."}, {"id":"II/0016","type":"II","opinion":"2009-06-25","decision":"2009-07-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"This type II variation concerns an update of the SPC, upon request by the CHMP following the assessment of PSU 22 (4th PSUR), to add information to sections 4.4 and 4.8 to reflect that in vitro and in vivo platelet assays suggest that Sprycel treatment may reversibly affect platelet activation, to add the ADR 'subdural haematoma' to section 4.8, and to make changes to the format of the presentation of safety data in section 4.8. Further, the MAH has implemented consequential editorial changes to the SPC."}, {"id":"II/0014","type":"II","opinion":"2009-01-22","decision":"2009-02-26","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Detailed Description of the Pharmacovigilanc e System"}, {"id":"II/0010","type":"II","opinion":"2009-01-22","decision":"2009-02-26","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","4.9","5.1"],"scope":"This type II variation concerns an update of sections 4.2, 4.4, 4.8, 4.9 and 5.1 of the SPC with 24-months follow-up data from two Phase 3 studies comparing the efficacy and safety of dasatinib administered once daily (QD) versus twice daily (BID) (current posology for the advanced phase CML and Ph+ALL indications) in subjects with chronic phase CML (CA180034) and advanced phase CML or Ph+ ALL (CA180035). The Package Leaflet has beeen amended accordingly. In addition, the MAH took the opportunity to provide an updated version of the RMP (version 6.0). Consequently, annex II has been updated to reflect the latest version agreed with the CHMP."}, {"id":"II/0012","type":"II","opinion":"2008-12-18","decision":"2009-02-10","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"This type II variation concerns an update of section 5.1 of the SPC, following the CHMP assessment of FU2 009.1, with results from the analyses of molecular response data after 24 months of follow-up at a dose of 70 mg dasatinib twice daily (BID) for advanced phase CML and Ph+ ALL patients from phase II studies CA180005, CA1800006 and CA180015. In patients with accelerated Phase CML, the rate of major molecular response (assessed in 41 patients with a CCyR) was 46% at 24 months. In patients with myeloid Blast Phase CML, the rate of major molecular response (assessed in 19 patients with a CCyR) was 68% at 24 months."}, {"id":"II/0013","type":"II","opinion":"2008-12-18","decision":"2009-01-29","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"This type II variation concerns an update of section 5.3 of the SPC, upon request by the CHMP following the assessment of FUM 004, to include further information on in vivo phototoxicity based on the results of study DS 071387."}, {"id":"II/0009","type":"II","opinion":"2008-11-20","decision":"2009-01-15","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"This type II variation concerned an update of section 5.3 of the SPC, upon request by the CHMP following the assessment of FUM 003 and FU2 003.1, with the results of an oral study of fertility and early embryonic development in rats (segment 1). In this study, dasatinib did not affect male or female fertility, but induced embryolethality at dose levels approximating human clinical exposures. In embryofoetal development studies, dasatinib likewise induced embryolethality with associated decreases in litter size in rats, as well as foetal skeletal alterations in both rats and rabbits."}, {"id":"X/0007","type":"X","opinion":"2008-10-23","decision":"2009-01-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH applied for an additional strength of 100 mg of film-coated tablets."}, {"id":"IB/0011","type":"IB","opinion":"2008-11-13","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0008","type":"II","opinion":"2008-05-30","decision":"2008-07-22","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"The MAH applied for a type II variation to update sections 4.4, 4.8 and 5.1 of the SPC with 24-months follow-up data from phase II studies CA180005, CA180006, CA180013, CA180015 and CA180017. The Package Leaflet has been amended accordingly. Further, the Marketing Authorisation Holder (MAH) has updated annex IIB to include a reference to the Pharmacovigilanc e system (version 2.5) and the Risk Management Plan (version 3.0) agreed with the CHMP. In addition, the MAH have implemented some minor editorial changes in the SPC and annex II and took the opportunity to update the contact details of the local representative for Romania in the Package Leaflet."}, {"id":"N/0004","type":"N","opinion":"2007-11-26","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0003","type":"IA","opinion":"2007-11-20","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement/add. of manufacturing site: Primary packaging site - Solid forms; Change in BR/QC testing - repl./add. manuf. responsible for BR - incl. BC/testing"}, {"id":"II/0002","type":"II","opinion":"2007-07-19","decision":"2007-08-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","4.9","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8, 4.9 and 5.1 of the SPC in line with the first results at 6 months of follow-up of the ongoing studies CA180034 and CA 180035. Furthermore, the MAH took the opportunity to update section 4.8 of the SPC in line with the outcome of the CHMP assessment of the 1st PSUR and according to MedDRA version 8.2. The Package Leaflet has been amended accordingly. In addition, the MAH has implemented some minor editorial changes in the annexes and updated the contact details of the local representatives for Romania and Denmark in the Package Leaflet."}, {"id":"N/0001","type":"N","opinion":"2007-02-15","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "datopotamab-deruxtecan__datroway": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/datroway-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000325249","type":"IAIN","opinion":"2026-02-09","decision":"2026-07-29","affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.) - Implementation of the agreed wording"}, {"id":"EMA/VR/0000319315","type":"IA","opinion":"2025-12-16","decision":"2026-07-29","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)"}, {"id":"EMA/VR/0000316654","type":"II","opinion":"2026-06-25","decision":"2026-07-29","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include, as monotherapy, the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy for DATROWAY, based on final results from study D926PC00001 (TROPION-Breast02). This is a Phase 3, randomised, open-label, 2 arm, multicentre, international study assessing the efficacy and safety of Dato-DXd compared with investigator's choice chemotherapy in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated."}, {"id":"EMA/VR/0000297245","type":"IB","opinion":"2025-10-20","decision":"2026-07-29","affects":["Annex II","PL"],"codes":["B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - Implementation of a change for a biological/immunological medicinal product"}, {"id":"EMA/VR/0000272686","type":"IB","opinion":"2025-06-24","decision":"2026-07-29","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"} ] }, "degarelix__firmagon": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/firmagon-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"N/0040","type":"N","opinion":"2022-02-07","decision":"2023-03-06","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0041","type":"IAIN","opinion":"2022-03-30","decision":"2023-03-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0039/G","type":"II","opinion":"2021-09-16","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","5.1"],"scope":"Extension of indications to include: • Extension of indication to include treatment of high-risk localized and locally advanced hormone dependent prostate cancer in combination with radiotherapy. As a consequence, sections 4.1, 4.2, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. • Extension of indication to include treatment as neo-adjuvant prior to radiotherapy in patients with high-risk localised or locally advanced hormone dependent prostate cancer. As a consequence, sections 4.1, 4.2, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0037","type":"II","opinion":"2020-07-09","decision":"2021-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Annex II to revise risk minimisation measures based on previous and a newly submitted study. As a consequence, the RMP is updated accordingly. The MAH took the occasion to transfer to GVP V revision 2 of the RMP, to align the PI to QRD template v.10.1 and propose combination of different strengths."}, {"id":"N/0033","type":"N","opinion":"2018-07-25","decision":"2019-12-16","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0031","type":"N","opinion":"2017-04-24","decision":"2019-12-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUV/0023","type":"PSUV","opinion":"2014-09-25","decision":"2014-11-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"N/0021","type":"N","opinion":"2014-01-29","decision":"2014-11-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0024","type":"IAIN","opinion":"2014-07-01","decision":"2014-11-21","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"R/0018","type":"R","opinion":"2013-09-19","decision":"2013-11-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUV/0020","type":"PSUV","opinion":"2013-09-19","decision":"2013-11-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0016","type":"II","opinion":"2013-04-25","decision":"2013-11-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC with PK data based on the results of CS38 trial."}, {"id":"II/0015","type":"II","opinion":"2013-07-25","decision":"2013-11-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the results from studies CS21/CS21A, CS30, CS31 and CS37. Furthermore, the MAH took the opportunity to add the local representative for Croatia in the Package Leaflet."}, {"id":"II/0014/G","type":"II","opinion":"2013-04-25","decision":"2013-11-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.3.a"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with data on effect of degarelix on QT/QTc supported by the results of the study CS22 (FUM 030). In addition, section 4.4 of the SmPC has been updated to delete the statement that data available on degarelix is limited to one year based on the results of the long term studies CS12A, CS14A and CS21A. Furthermore, section 4.8 of the SmPC has been updated to include anaphylaxis reactions further to the request of the CHMP during the assessment of the 4th PSUR. The package leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0011","type":"II","opinion":"2012-05-24","decision":"2012-06-28","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the intermediate container closure system for the solvent (water for injections), to replace glass vials with glass pre-filled syringes. In addition the applicant took an opportunity to align the Product Information with the current QRD template."}, {"id":"IA/0006/G","type":"IA","opinion":"2010-06-18","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.IV.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change of a measuring or administration device - Addition or replacement of a device which is not an integrated part of the primary packaging - Device with CE marking"}, {"id":"IB/0003","type":"IB","opinion":"2010-02-09","decision":"2010-02-09","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units outside range of appr. pack size"}, {"id":"II/0001","type":"II","opinion":"2009-06-25","decision":"2009-07-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of SPC section 4.8 to include numerous adverse drug reactions (ADRs) from Phase 2 and 3 trials following a request by the CHMP at the time of the original marketing authorisation. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to add the MA date and numbers in the SPC and Labelling as well as to update the List of Local Representatives for Bulgaria in the English Package Leaflet."} ] }, "dinutuximab-beta__qarziba-previously-dinutuximab-beta-eusa-and-dinutuximab-beta-apeiron-": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/qarziba-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/qarziba-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000316241","type":"II","opinion":"2026-09-17","decision":"2026-10-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.13","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"A grouped application, comprised of the following variations: Update of sections 4.8, 5.1 and 5.2 of the SmPC to introduce changes based on the final results from study APN311-304; this is a Phase II, interventional, single-arm, open-label study evaluating the anti-tumor activity and safety of dinutuximab beta (ch14.18/CHO) continuous infusion in pediatric patients with primary refractory or relapsed neuroblastoma. The Package Leaflet has been updated accordingly."}, {"id":"EMA/VR/0000312776","type":"IAIN","opinion":"2025-11-26","decision":"2026-04-16","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"EMA/VR/0000263543","type":"IA","opinion":"2025-04-07","decision":"2026-04-16","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"II/0043","type":"II","opinion":"2023-10-12","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.1","4.2","5.1"],"scope":"Update of sections 4.1, 4.2 and 5.1 of the SmPC based on final results from study APN311-202V3 listed as a Specific Obligation in the Annex II of the Product Information. This is a Phase I/II dose schedule finding study of Ch14.18/CHO continuous infusion combined with subcutaneous aldesleukin (IL-2) in patients with primary refractory or relapsed neuroblastoma. In addition, the MAH took the opportunity to update Annex II section E. The Package Leaflet is updated accordingly."}, {"id":"IAIN/0054/G","type":"IAIN","opinion":"2023-07-17","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.2.c.1","B.II.b.1.a","A.5.b","A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Change in the name and/or address of the MAH"}, {"id":"IB/0051/G","type":"IB","opinion":"2023-03-31","decision":null,"affects":["SmPC"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0044","type":"II","opinion":"2022-12-15","decision":"2023-01-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC with new safety information regarding central nervous system toxicity based on post-marketing safety report and literature. The package leaflet of the Product Information is amended accordingly."}, {"id":"S/0046","type":"S","opinion":"2022-10-13","decision":"2022-12-09","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0045","type":"II","opinion":"2022-09-01","decision":"2022-12-09","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0027/G","type":"II","opinion":"2021-09-16","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":["A.6","C.I.11.b","C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required; Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0025","type":"IAIN","opinion":"2021-03-29","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"N/0012","type":"N","opinion":"2019-03-12","decision":"2020-06-09","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0019","type":"IB","opinion":"2019-12-19","decision":"2020-06-09","affects":["SmPC","Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0014/G","type":"IAIN","opinion":"2019-06-07","decision":"2020-06-09","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0018/G","type":"IA","opinion":"2019-11-21","decision":"2020-06-09","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"T/0010","type":"T","opinion":"2019-01-28","decision":"2019-03-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0005","type":"IB","opinion":"2018-03-05","decision":"2018-07-19","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0003","type":"IAIN","opinion":"2017-11-27","decision":"2018-07-19","affects":["SmPC","Labelling","PL"],"codes":["A.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the (invented) name of the medicinal product for CAPs"}, {"id":"IAIN/0002","type":"IAIN","opinion":"2017-08-04","decision":"2018-07-19","affects":["SmPC","Labelling","PL"],"codes":["A.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the (invented) name of the medicinal product for CAPs"}, {"id":"T/0001","type":"T","opinion":"2017-06-15","decision":"2017-07-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "dostarlimab__jemperli": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/jemperli-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/jemperli-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000357436","type":"IB","opinion":"2026-09-25","decision":null,"affects":["SmPC","PL"],"codes":["Q.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"EMA/VR/0000335826","type":"IB","opinion":"2026-03-31","decision":"2026-06-04","affects":["SmPC"],"codes":["Q.II.f.1.b.1","Q.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol); Change in the shelf life or storage - Change to an approved stability protocol of the finished product"}, {"id":"EMA/VR/0000303403","type":"II","opinion":"2026-04-10","decision":"2026-06-04","affects":["Annex II","PL"],"codes":["B.I.a.3.c","B.I.a.1.e","B.I.a.1.j","B.I.b.2.e","B.I.c.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in batch size (including batch size ranges) of active substance or intermediate used in the manufacturing process of the active substance - The change requires assessment of the comparability of a biological/immunological active substance; Change in the manufacturer of a starting material/reagent/intermediate used in the manufacturing process of the active substance or change in the manufacturer (including where relevant quality control testing sites) of the active substance, where no Ph."}, {"id":"EMA/VR/0000296756","type":"II","opinion":"2026-04-23","decision":"2026-06-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the Zejula SmPC and update of sections 4.2, 5.1 and 5.2 of the Jemperli SmPC to include the final results from study 213406 (SCOOP) in order to complete the PIPs EMA/PE/0000270085 for Jemperli and EMA/PE/0000269425 for Zejula and in order to fulfil Article 46 of Regulation EC No 1901/2006. Study 213406 (SCOOP) is a phase 1, multicentre, open-label, dose escalation and cohort expansion study of niraparib and dostarlimab in paediatric participants with recurrent or refractory solid tumours. the Package Leaflet is updated accordingly."}, {"id":"PSUSA/00010931/202504","type":"PSUSA","opinion":"2025-12-11","decision":"2026-02-10","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - dostarlimab"}, {"id":"EMA/VR/0000256521","type":"II","opinion":"2025-06-05","decision":"2025-09-15","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated to add the new manufacturer responsible for batch release: GlaxoSmithKline Manufacturing S.p.A Strada Provinciale Asolana, 90, 43056 San Polo di Torrile Parma, Italy"}, {"id":"EMA/T/0000292052","type":"T","opinion":"2025-09-01","decision":"2025-09-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from GlaxoSmithKline (Ireland) Limited to GlaxoSmithKline Trading Services Limited"}, {"id":"II/0040","type":"II","opinion":"2025-04-25","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0038/G","type":"II","opinion":"2024-11-21","decision":"2025-01-15","affects":["Annex II"],"codes":["B.I.c.1.b","B.I.a.1.k","B.I.a.1.j","B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the AS - Qualitative and/or quantitative composition for sterile and non-frozen biological/immunological ASs; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - New storage site of MCB and/or WCB; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Replacement or addition of a site where batch control/testing takes place and any of the test method at the site is a biol/immunol method."}, {"id":"II/0032","type":"II","opinion":"2024-12-12","decision":"2025-01-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for JEMPERLI to include, in combination with carboplatin and paclitaxel, the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy based on Interim Analysis 1 and 2 from study RUBY Part 1 (213361). This is a phase 3, randomized, double-blind, controlled study evaluating the efficacy and safety of dostarlimab plus carboplatin and paclitaxel in primary advanced or recurrent EC versus placebo plus carboplatin and paclitaxel. As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated. The Annex II.D and Package Leaflet are updated in accordance."}, {"id":"II/0031","type":"II","opinion":"2024-05-30","decision":"2025-01-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0037","type":"IAIN","opinion":"2024-07-30","decision":"2025-01-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0035","type":"IAIN","opinion":"2024-07-30","decision":"2025-01-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0023","type":"II","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with carboplatin and paclitaxel the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy, based on results from study 213361 (RUBY) Part 1, listed as a Specific Obligation in the Annex II; this is a phase 3, randomized, double-blind, multicenter study of dostarlimab (TSR-042) plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in patients with recurrent or primary advanced endometrial cancer. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated."}, {"id":"II/0013","type":"II","opinion":"2022-12-15","decision":"2023-02-15","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy and safety information based on interim results from study 4010-01-001 (GARNET) listed as a specific obligation (SOB) in the Annex II; This is a single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumours. Update of Annex II to remove the specific obligation. In addition, the MAH took the opportunity to update Annex II in line with the QRD template version 10.3. The RMP version 2.1 is approved."}, {"id":"IB/0016","type":"IB","opinion":"2022-10-10","decision":"2023-02-15","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update Annex II in order to change the due date for the obligations and conditions of a marketing authorisation, including the RMP - Other variation efficacy study 'RUBY' from ’31 December 2022’ to ’31 August 2023’."}, {"id":"II/0009","type":"II","opinion":"2022-04-28","decision":"2022-09-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0007","type":"II","opinion":"2022-07-21","decision":"2022-09-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8","5.2"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to update dose modifications recommendations in immune related adverse reactions, amend existing warnings, and add further immune-related ADRs to the list of adverse drug reactions (ADRs), with different frequencies, based on data from company sponsored trials and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make minor changes to sections 4.6 and 5.2 of the SmPC and to update the list of local representatives in the Package Leaflet. Changes are also made to the PI to bring it in line with the current QRD template version and excipients guideline."}, {"id":"IB/0011/G","type":"IB","opinion":"2022-06-08","decision":"2022-09-13","affects":["SmPC","Labelling"],"codes":["B.II.f.1.b.1","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IB/0002","type":"IB","opinion":"2021-07-01","decision":"2022-02-16","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "durvalumab__imfinzi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/imfinzi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/imfinzi-epar-procedural-steps-taken-scientific-information-after-authorisation-archived_en.pdf"], "procedures": [ {"id":"EMA/VR/0000282058","type":"II","opinion":"2026-01-29","decision":"2026-03-12","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1"],"scope":"Extension of indication for IMFINZI to include in combination with FLOT chemotherapy as neoadjuvant and adjuvant treatment, followed by adjuvant IMFINZI monotherapy, for the treatment of adults with resectable gastric or gastro-oesophageal junction adenocarcinoma , based on interim results from study MATTERHORN, (D910GC00001); this is a randomized, double-blind, placebo-controlled, phase 3 study of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab in patients with resectable gastric and gastroesophageal junction cancer (GC/GEJC); As a consequence, sections 4.1, 4.2, 4.5, 4.8, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000296305","type":"IB","opinion":"2026-02-12","decision":null,"affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To extend the due date for the phase III PAES study D9311C00001 (DUO-E) from December 2026 to November 2028 in the RMP and Annex II of the SmPC. In addition, the MAH has taken this opportunity to correct an error identified for the DUO-E study involving a raw data mapping issue that affected the COVID-19 study disruption data and impacts the COVID-19 tables in the CSR. As there is no change in the interpretation or the overall conclusion this has exceptionally been included as part of this type IB."}, {"id":"II/0073","type":"II","opinion":"2025-05-22","decision":"2025-07-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by IMFINZI as monotherapy adjuvant treatment after radical cystectomy, for the treatment of adults with resectable muscle invasive bladder cancer (MIBC), based on an ongoing pivotal study D933RC00001 (NIAGARA); this is a phase 3, randomized, open-label, multi-center, global study to determine the efficacy and safety of durvalumab in combination with gemcitabine + cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in patients with muscle-invasive bladder cancer. As a consequence, sections 4.1, 4.2, 4.8, and 5.1 of the SmPC are updated."}, {"id":"II/0064","type":"II","opinion":"2025-02-27","decision":"2025-03-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the treatment in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements for IMFINZI, based on the interim results from study D9106C00001 (AEGEAN); this is a Phase III, double-blind, placebo-controlled, multi-center international study of neoadjuvant/adjuvant durvalumab for the treatment of patients with resectable stages II and III non-small cell lung cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated."}, {"id":"II/0069","type":"II","opinion":"2025-01-30","decision":"2025-03-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy for IMFINZI, based on results from study D933QC00001 (ADRIATIC); this is a phase III, randomized, double-blind, placebo-controlled, multi-centre, global study to assess the efficacy and safety of durvalumab monotherapy and durvalumab in combination with tremelimumab compared to placebo as consolidation treatment in patients with LS-SCLC whose disease had not progressed following definitive platinum-based chemoradiation therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated."}, {"id":"II/0067/G","type":"II","opinion":"2024-10-17","decision":"2025-02-12","affects":["Annex II"],"codes":["B.I.c.z","B.I.a.2.a","B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Container closure system of the AS - Other variation; Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product"}, {"id":"IAIN/0068/G","type":"IAIN","opinion":"2024-07-18","decision":"2025-02-12","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2463","type":"WS","opinion":"2024-06-27","decision":"2024-07-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to include paediatric information based on final results from study D419EC00001 “Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or Durvalumab in Combination with Tremelimumab in Pediatric Patients with Advanced Solid Tumors and Hematological Malignancies”. In addition, the MAH took this opportunity to introduce editorial changes."}, {"id":"II/0066","type":"II","opinion":"2024-05-30","decision":"2024-07-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4, and 4.8 of the SmPC in order to include rhabdomyolysis as an extension of the myositis and polymyositis medical concept based on post marketing data and literature."}, {"id":"WS/2650","type":"WS","opinion":"2024-04-25","decision":"2024-05-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.2 and 4.4 of the SmPC in order to simplify current dosing recommendations."}, {"id":"WS/2543","type":"WS","opinion":"2023-12-14","decision":"2024-02-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to include paediatric information based on final results from study D419EC00001 “Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or Durvalumab in Combination with Tremelimumab in Pediatric Patients with Advanced Solid Tumors and Hematological Malignancies”. In addition, the MAH took this opportunity to introduce editorial changes."}, {"id":"PSUSA/00010723/202304","type":"PSUSA","opinion":"2023-12-14","decision":"2024-02-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - durvalumab"}, {"id":"II/0057","type":"II","opinion":"2023-10-12","decision":"2023-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include IMFINZI as monotherapy for the treatment of adults with unresectable hepatocellular carcinoma (uHCC), based on final results from study D419CC00002 (HIMALAYA); this was a randomized, open-label, multi-center phase III study of durvalumab and tremelimumab as first-line treatment in patients with unresectable hepatocellular carcinoma (HIMALAYA). As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 9.1 of the RMP has also been submitted."}, {"id":"IAIN/0060","type":"IAIN","opinion":"2023-07-13","decision":"2023-11-15","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"R/0055","type":"R","opinion":"2023-02-23","decision":"2023-04-24","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0052","type":"II","opinion":"2022-12-15","decision":"2023-01-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to update the recommendation for dose modification for ‘other immune-mediated adverse reactions’ as well as immune-mediated encephalitis, meningitis, Guillain-Barré syndrome and myasthenia gravis based on the National Comprehensive Cancer Network (NCCN) guideline recommendations (2022)."}, {"id":"II/0045","type":"II","opinion":"2022-12-15","decision":"2023-01-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include IMFINZI in combination with tremelimumab for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (uHCC), based on final results from Study D419CC00002 (HIMALAYA); This was a randomized, open-label, multi-center phase III study of durvalumab and tremelimumab as first-line treatment in patients with unresectable hepatocellular carcinoma. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet. Version 8.1 of the RMP has also been submitted."}, {"id":"II/0041","type":"II","opinion":"2022-12-15","decision":"2023-01-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include first-line treatment, with Imfinzi in combination with tremelimumab and platinum-based chemotherapy, of adults with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) positive mutations, based on final results from Study D419MC00004 (POSEIDON); This was a Phase III, randomised, multicentre, open-label, comparative global study to determine the efficacy and safety of tremelimumab and durvalumab or durvalumab in combination with platinum based chemotherapy for first-line treatment in patients with metastatic NSCLC."}, {"id":"IAIN/0058","type":"IAIN","opinion":"2022-12-13","decision":"2023-01-30","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0050","type":"II","opinion":"2022-09-29","decision":"2022-12-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0046","type":"II","opinion":"2022-11-10","decision":"2022-12-16","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include IMFINZI in combination with gemcitabine and cisplatin for the first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC), based on the second interim analysis from the ongoing pivotal study D933AC00001 (TOPAZ-1); a phase III randomized, double-blind, placebo-controlled, multi-regional, international study conducted to assess the efficacy and safety of durvalumab in combination with the current standard of care Gemcitabine/Cisplatin for the first-line treatment of patients with locally advanced or metastatic BTC."}, {"id":"PSUSA/00010723/202110","type":"PSUSA","opinion":"2022-06-23","decision":"2022-08-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - durvalumab"}, {"id":"II/0034","type":"II","opinion":"2022-06-23","decision":"2022-08-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to reflect the outcome of the re-defined process to identify and calculate immune-mediated Adverse Event (imAE) rates from clinical study and pooled datasets within the durvalumab development programmes. In addition, the MAH implemented minor editorial corrections to sections 4.4 and 5.1 of the SmPC."}, {"id":"II/0040","type":"II","opinion":"2022-02-17","decision":"2022-06-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0039/G","type":"II","opinion":"2022-04-22","decision":"2022-06-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0044/G","type":"IAIN","opinion":"2022-04-06","decision":"2022-06-13","affects":["SmPC","PL"],"codes":["A.6","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010723/202104","type":"PSUSA","opinion":"2021-12-16","decision":"2022-02-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - durvalumab"}, {"id":"IAIN/0035","type":"IAIN","opinion":"2021-09-22","decision":"2022-02-28","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0030/G","type":"II","opinion":"2021-09-16","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2. and 4.4 the SmPC in order to change posology recommendations for management of immune-mediated adverse reactions and amend an existing warning on Immune-mediated type 1 diabetes mellitus to include diabetic ketoacidosis; these changes are based on case studies reports, updated guidelines. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make some minor corrections to section 4.8 of the SmPC."}, {"id":"II/0026","type":"II","opinion":"2021-02-11","decision":"2021-10-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0031/G","type":"IB","opinion":"2021-07-07","decision":"2021-10-19","affects":["SmPC","Annex II","PL"],"codes":["B.II.f.1.b.3","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"The product information was updated to extend the shelf life after diluation and the manufacturers responsible for batch release were updated.."}, {"id":"II/0024","type":"II","opinion":"2020-12-10","decision":"2021-01-11","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add immune thrombocytopenia to the list of adverse drug reactions (ADRs) with frequency (rare) following the MAH internal review; the Package Leaflet (PL) is updated accordingly. The MAH took the opportunity to correct information in the PL and to make editorial changes to the names of the manufacturer in Annex II and to units in Annex IIIA."}, {"id":"II/0023","type":"II","opinion":"2020-12-10","decision":"2021-01-11","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC in order to introduce a new posology regimen of 1500 mg every 4 weeks (Q4W) for the approved indication of the treatment of patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum based chemoradiation therapy. The RMP version 4.1 has also been submitted."}, {"id":"II/0014/G","type":"II","opinion":"2020-07-23","decision":"2020-08-27","affects":["SmPC","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include the use of IMFINZI in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC were updated. The proposed indication is supported by study D419QC00001 (CASPIAN), an ongoing Phase III randomised, multicentre, open-label, comparative study designed to determine the efficacy and safety of durvalumab, or durvalumab and tremelimumab, in combination with etoposide and platinum-based chemotherapy (EP) for the first-line treatment of patients with ES-SCLC."}, {"id":"PSUSA/00010723/201910","type":"PSUSA","opinion":"2020-05-28","decision":"2020-07-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - durvalumab"}, {"id":"IAIN/0021","type":"IAIN","opinion":"2020-05-13","decision":"2020-07-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010723/201904","type":"PSUSA","opinion":"2019-12-12","decision":"2020-02-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - durvalumab"}, {"id":"II/0009","type":"II","opinion":"2019-09-12","decision":"2020-02-21","affects":["SmPC","PL"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"IAIN/0015","type":"IAIN","opinion":"2019-12-10","decision":"2020-02-21","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0008","type":"IAIN","opinion":"2019-04-08","decision":"2020-02-21","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "elacestrant__orserdu": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/orserdu-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/orserdu-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000321500","type":"II","opinion":"2026-06-25","decision":"2026-07-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4, and 5.2 of the SmPC in order to add a dose recommendation for patients with severe hepatic impairment and update pharmacokinetic information based on the results from study STML-ELA-1023 and PBPK modelling. STML-ELA-1023 is a phase 1, open-label, non-randomized, parallel-group study to evaluate the pharmacokinetics, safety and tolerability of a single oral dose of 200 mg elacestrant in subjects with normal hepatic function or severe hepatic impairment. The MAH took the opportunity to introduce minor editorial corrections in SmPC section 5.2."}, {"id":"EMA/N/0000338142","type":"N","opinion":"2026-03-25","decision":"2026-07-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representative."}, {"id":"EMA/N/0000304207","type":"N","opinion":"2025-10-13","decision":"2026-07-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"II/0009","type":"II","opinion":"2025-01-16","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to provide additional pharmacokinetic information following the PAM procedure for study MRPO-2023-PDE004 and based on the report SLP 43753974; this is an assessment of the potential role of P-glycoprotein in the supra-proportional exposure of elacestrant and the potential impact of P-glycoprotein inhibitors on elacestrant exposure at the dose of 100 mg. In addition, the MAH took the opportunity to introduce editorial changes to the PI and to bring the PI in line with the latest QRD template version 10.4."}, {"id":"IB/0005","type":"IB","opinion":"2024-05-22","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"N/0002","type":"N","opinion":"2024-02-13","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "elotuzumab__empliciti": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/empliciti-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/empliciti-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IB/0035","type":"IB","opinion":"2023-06-01","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IA/0034","type":"IA","opinion":"2023-03-03","decision":null,"affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"II/0028","type":"II","opinion":"2021-10-21","decision":"2022-10-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy data from the final CSR for study CA204125. This is a open label, randomized phase 2 Trial of Pomalidomide/Dexamethasone With or Without Elotuzumab in RRMM. In addition, the MAH took the opportunity to remove the list of local representatives in the Package Leaflet and update the address of the manufacturer."}, {"id":"IAIN/0030/G","type":"IAIN","opinion":"2022-02-15","decision":"2022-10-14","affects":["SmPC","Annex II","PL"],"codes":["A.4","A.5.a","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0024","type":"R","opinion":"2020-10-15","decision":"2020-12-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0018","type":"II","opinion":"2019-09-26","decision":"2020-10-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with final overall survival data from study CA204004 (A Phase 3, Randomized, Open Label Trial of lenalidomide/dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma)."}, {"id":"IAIN/0023","type":"IAIN","opinion":"2020-04-20","decision":"2020-10-19","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0012","type":"II","opinion":"2019-07-25","decision":"2019-08-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","4.9","5.1","5.2","6.6"],"scope":"Extension of Indication to include treatment in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.6, 4.8, 4.9, 5.1, 5.2 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet. The RMP (version 2.1) is updated to reflect the new indication."}, {"id":"II/0013","type":"II","opinion":"2019-02-28","decision":"2019-04-02","affects":["Annex II","PL"],"codes":["B.II.b.2.c.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing for a biol/immunol product and any of the test methods is a biol/immunol/immunochemical method"}, {"id":"IG/1059","type":"IG","opinion":"2019-02-15","decision":"2019-04-02","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0006","type":"II","opinion":"2017-07-13","decision":"2017-10-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0001/G","type":"II","opinion":"2016-11-10","decision":"2017-10-04","affects":["SmPC","Annex II","Labelling"],"codes":["A.6","B.I.a.1.e","B.I.a.1.f","B.I.a.3.c","B.I.a.4.b","B.I.a.4.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"1) IA -A.6 - to add the ATC Code following granting by WHO in the SmPC and bring the labelling in line with the latest QRD template (V10.0). 2) II- B.I.a.1.e – to add BMS-Devens as an alternate active substance manufacturer. 3) IB- B.I.a.1.f –to add BioReliance, Rockville, MD as alternative in-process testing site for preharvest samples for Mycoplasma, in vitro adventitious virus and MVM (Minute Virus of Mice) testing. 4) II- B.I.a.3.c – to increase (5-fold) the batch size of elotuzumab drug substance from 5,000 L to 25,000 L at BMS-Devens site. 5) IB -B.I.a.4.b – to implement of a new in-process control for Triton X-100 at both, BMS-Syracuse and BMS-Devens sites. 6) II-B.I.a.4.d – to widen…"} ] }, "elranatamab__elrexfio": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/elrexfio-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/elrexfio-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000294591","type":"II","opinion":"2025-11-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add progressive multifocal leukoencephalopathy to the list of adverse drug reactions (ADRs) with the frequency uncommon based on clinical trials and post-marketing data-sources. In accordance with the updated data cut-off of September 10, 2024, the incidence rates for all listed adverse reactions have been revised. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000285949","type":"IB","opinion":"2025-07-21","decision":"2025-09-10","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/VR/0000278463","type":"IAIN","opinion":"2025-09-11","decision":"2025-09-10","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000246959","type":"IB","opinion":"2025-04-04","decision":"2025-09-10","affects":["SmPC","PL"],"codes":["B.II.f.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - After first opening (supported by real time data)"}, {"id":"II/0005","type":"II","opinion":"2025-03-27","decision":"2025-05-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of section 4.2 of the SmPC to add every four-week dosing schedule after at least 24 weeks of every two-week dosing and to update the recommendations for restarting therapy following dose delay, and update of sections 4.8, 5.1 and 5.2 of the SmPC with long-term efficacy, safety, and clinical pharmacology results (≥2 years of follow-up after the last participant initial dose), based on the final study report of Study C1071003; a Phase 2, open-label, multicentre, non-randomised study of elranatamab monotherapy in participants with MM who are refractory to at least one PI, one IMiD, and one anti-CD38 Ab. The Package Leaflet has been updated in accordance."}, {"id":"PSUSA/00000225/202402","type":"PSUSA","opinion":"2024-09-19","decision":"2024-11-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - elranatamab"} ] }, "encorafenib__braftovi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/braftovi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/braftovi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000304994","type":"II","opinion":"2026-05-21","decision":"2026-06-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include, in combination with cetuximab and FOLFOX, the first line treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation for BRAFTOVI, based on the interim results from the pivotal Study C4221015 (BREAKWATER). This is an open-label, multicenter, 3-arm, randomized Phase 3 study of encorafenib plus cetuximab (EC)"}, {"id":"EMA/VR/0000241083","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.2"],"scope":"Update of section 4.2 and 5.2 of the SmPC in order to update paediatric information following PIP compliance check (EMEA-C-001588-PIP01-13- M03 and EMEA-C-001454-PIP03-15-M03). In addition, the MAH took the opportunity to implement a minor correction in section 4.8 of the SmPC."}, {"id":"EMA/VR/0000256240","type":"II","opinion":"2025-05-15","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the description of most common adverse drug reactions in the special populations, Elderly, for the indication Colorectal Cancer after an error was identified by the Sponsor."}, {"id":"WS/2658","type":"WS","opinion":"2024-11-14","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of sections 5.1 of the SmPC in order to update efficacy and safety information following the outcome of procedures 004579/0000 and R/0024 based on final results from study C4221004 (CMEK162B2301). This was a 2-part, multi-center, randomized, open label, Phase III study comparing the efficacy and safety of encorafenib plus binimetinib to vemurafenib and encorafenib monotherapy in participants with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"WS/2538","type":"WS","opinion":"2024-07-25","decision":"2024-08-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include binimetinib in combination with encorafenib for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600E mutation for MEKTOVI and BRAFTOVI based on results from study PHAROS (Study ARRAY-818-202) at the primary completion date; this is a Phase II, open-label, multicentre, non-comparative study (interventional). As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the Braftovi SmPC and sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the Mektovi SmPC are updated. The Package Leaflet is updated in accordance. Version 3.0 of Braftovi and Mektovi RMPs have also been approved."}, {"id":"II/0031","type":"II","opinion":"2023-12-14","decision":"2024-03-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"R/0029","type":"R","opinion":"2023-04-26","decision":"2023-06-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0026","type":"II","opinion":"2022-06-23","decision":"2022-07-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to introduce a new scheme of encorafenib dose reduction recommendations for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, by replacing the second dose reduction level of 200 mg once daily by 225 mg once daily; based on results from simulation report (ARRA-CSC-104). In addition, the MAH took the opportunity to introduce an update of the user instructions in the Package Leaflet for increased clarity."}, {"id":"IAIN/0025","type":"IAIN","opinion":"2022-01-24","decision":"2022-07-25","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0020","type":"II","opinion":"2021-10-14","decision":"2022-01-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to add drug-drug interaction information with rosuvastatin and bupropion based on final results from Arm 2 of study ARRAY-818-103. This is a Phase 1, three-arm, open-label drug-drug interaction study in patients with BRAF V600-mutant unresectable or metastatic melanoma or other BRAF V600-E and/or K-mutant advanced solid tumours."}, {"id":"IB/0017","type":"IB","opinion":"2021-01-11","decision":"2022-01-06","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Qualitative and quantitative composition - Solid pharmaceutical forms"}, {"id":"IA/0021","type":"IA","opinion":"2021-08-09","decision":"2022-01-06","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IA/0019/G","type":"IA","opinion":"2021-03-31","decision":"2022-01-06","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"WS/1695","type":"WS","opinion":"2020-04-30","decision":"2020-06-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include encorafenib in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, who have received prior systemic therapy, as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP version 2.0 is acceptable. Furthermore, the PI is brought in line with the latest QRD template version 10.1. Note: The MAH in the course of the assessment withdrew Mektovi (binimetinib) from the applied indication. Therefore, the extension of indication only concerns the product Braftovi (encorafenib)."}, {"id":"IAIN/0007/G","type":"IAIN","opinion":"2019-10-14","decision":"2020-06-02","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IB/0004/G","type":"IB","opinion":"2019-04-23","decision":"2019-10-29","affects":["SmPC","PL"],"codes":["A.6","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0001/G","type":"IB","opinion":"2018-11-07","decision":"2019-10-29","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "enfortumab-vedotin__padcev": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/padcev-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/padcev-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000336191","type":"II","opinion":"2026-09-17","decision":"2026-10-15","affects":["SmPC","PL"],"codes":["C.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include Padcev, in combination with pembrolizumab, as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment, is indicated for the treatment of adults with resectable muscle invasive bladder cancer (MIBC) who are eligible for cisplatin-containing chemotherapy, based on the results from Interim Analysis 1 of the pivotal Study KN-B15 (EV-304); this is a phase 3, randomized, open-label study to evaluate perioperative enfortumab vedotin plus pembrolizumab (MK-3475) versus neoadjuvant gemcitabine and cisplatin in cisplatin-eligible participants with Muscle-Invasive Bladder Cancer."}, {"id":"PSUSA/00010989/202512","type":"PSUSA","opinion":"2026-07-23","decision":"2026-09-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - enfortumab vedotin"}, {"id":"EMA/VR/0000339461","type":"II","opinion":"2026-07-16","decision":"2026-09-21","affects":["Annex II"],"codes":["Q.I.a.1.d","Q.I.a.1.i","Q.II.b.2.a","Q.II.b.2.b","Q.II.d.2.d","Q.II.b.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing site of a starting material/intermediate used in the manufacturing process of the active substance or change in the manufacturing site (including where relevant quality control testing sites) of the active substance - Addition or replacement of a manufacturing site of - a biological active substance or - a biological starting material/reagent/raw material/intermediate used in the manufacture of a biological active substance which may have a significant impact on the quality, safety or efficacy of the finished product or - a material for which an assessment is required of viral safety and/or TSE risk."}, {"id":"EMA/VR/0000312495","type":"II","opinion":"2026-05-21","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include PADCEV in combination with pembrolizumab, as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment of adults with resectable muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin containing chemotherapy, based on interim results from study KEYNOTE-905, an open label, randomised, interventional phase 3 study. As consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 5.3 of the RMP has also been agreed."}, {"id":"PSUSA/00010989/202412","type":"PSUSA","opinion":"2025-07-24","decision":"2025-09-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - enfortumab vedotin"}, {"id":"II/0021/G","type":"II","opinion":"2024-12-05","decision":null,"affects":["SmPC"],"codes":["B.I.a.1.g","B.I.a.2.z","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Introduction of a new manufacturer of the AS that is not supported by an ASMF and requires significant update to the relevant AS section in the dossier; Changes in the manufacturing process of the AS - Other variation; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0020","type":"II","opinion":"2024-11-28","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add skin hyperpigmentation, skin discoloration, pigmentation disorder with frequency 'not known' based on available clinical, post marketing, and preclinical data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"PSUSA/00010989/202312","type":"PSUSA","opinion":"2024-07-25","decision":"2024-09-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - enfortumab vedotin"}, {"id":"II/0016","type":"II","opinion":"2024-09-05","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6"],"scope":"Update of sections 4.4 and 4.6 of the SmPC in order to update information on contraception for males and females in line with the SWP/NcWP (EMA/CHMP/SW P/74077/2020 rev. 1) recommendations on the duration of contraception following the end of treatment with a genotoxic drug. The Package Leaflet is updated accordingly."}, {"id":"N/0011","type":"N","opinion":"2023-11-29","decision":"2024-08-26","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0013","type":"II","opinion":"2024-07-25","decision":"2024-08-26","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3","6.6"],"scope":"Extension of indication to include PADCEV in combination with pembrolizumab, the first-line treatment of adult patients with locally advanced or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy, based on the final results from study KEYNOTE-A39/EV-302. This was an open label, randomized, controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab versus chemotherapy alone in previously untreated locally advanced (LA) or metastatic urothelial cancer (mUC)”. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2, 5.3 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0007","type":"II","opinion":"2023-03-30","decision":"2023-04-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to introduce new posology recommendations in case of pneumonitis/interstitial lung disease (ILD), add a new warning on ‘pneumonitis/ILD’ and add it to the list of adverse drug reactions (ADRs). The Package Leaflet is updated accordingly. The RMP version 2.0 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."} ] }, "entrectinib__rozlytrek": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/rozlytrek-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/rozlytrek-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000379479","type":"IB","opinion":"2026-11-03","decision":null,"affects":["SmPC","PL"],"codes":["Q.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf life of the finished product based on extrapolation of stability data in accordance with relevant stability guidelines"}, {"id":"PSUSA/00010874/202406","type":"PSUSA","opinion":"2025-01-30","decision":"2025-03-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - entrectinib"}, {"id":"X/0017/G","type":"X","opinion":"2024-04-25","decision":"2024-06-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a","C.I.4"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","6.3","6.4","6.6"],"scope":"Extension of the currently approved indication of Rozlytrek in solid tumours with NTRK gene fusion to patients from 1 month to 12 years of age (both for the coated granules and already approved hard capsules presentations). Based on final results from studies CO40778 (STARTRK-NG), GO40782 (STARTRK-2) and BO41932 (TAPISTRY). Study CO40778 is a Phase I/II open-label, dose-escalation and expansion study of entrectinib in paediatrics with locally advanced or metastatic solid or primary CNS tumours and/or who have no satisfactory treatment options."}, {"id":"R/0020","type":"R","opinion":"2024-03-21","decision":"2024-05-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"R/0015","type":"R","opinion":"2023-04-26","decision":"2023-07-07","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0014","type":"II","opinion":"2023-01-26","decision":"2023-03-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update the pharmacokinetic information based on final results from study GP411174 listed as an additional pharmacovigilance activity in the RMP; this is a Phase I, non-randomized, single-dose, open-label study to investigate the effect of impaired hepatic function on the pharmacokinetics of entrectinib in volunteers with different levels of hepatic function. The RMP version 4.1 has also been agreed. In addition, the MAH took the opportunity to update in Annex II section C and to update the list of local representatives in the Package Leaflet."}, {"id":"II/0012","type":"II","opinion":"2022-09-08","decision":"2023-03-09","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Submission of the final integrated analysis report for cardiac risks, listed as a category 3 study in the RMP, in order to fulfil MEA/003. This is an integrated safety analysis report to assess cardiac risks based on GO40782 [STARTRK-2], CO40778 [STARTRK-NG], and BO41932 [TAPISTRY] studies (PAESs). Section 4.4 of the SmPC has been updated to better reflect the cardiac safety findings."}, {"id":"IB/0011/G","type":"IB","opinion":"2022-06-27","decision":"2023-03-09","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"R/0007","type":"R","opinion":"2022-03-24","decision":"2022-05-30","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0005/G","type":"IB","opinion":"2021-08-10","decision":"2022-05-30","affects":["SmPC","PL"],"codes":["A.6","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0001","type":"IB","opinion":"2020-10-15","decision":"2021-06-21","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "enzalutamide__xtandi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/xtandi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/xtandi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000362594","type":"N","opinion":"2026-07-28","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"EMA/VR/0000313098","type":"II","opinion":"2026-02-12","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to reflect the updated safety and efficacy data based on final results from 9785-CL-0335 (EMBARK) study; this is a phase 3, randomized, double-blind, placebo-controlled efficacy and safety study of enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC); the Package Leaflet is updated accordingly. The RMP version 21.0 has also been submitted."}, {"id":"EMA/VR/0000289609","type":"IAIN","opinion":"2025-07-31","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"II/0068/G","type":"II","opinion":"2025-01-16","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Grouped application comprising two type II variations as follows:"}, {"id":"PSUSA/00010095/202308","type":"PSUSA","opinion":"2024-04-25","decision":"2024-06-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - enzalutamide"}, {"id":"IAIN/0066","type":"IAIN","opinion":"2024-06-06","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0063","type":"II","opinion":"2024-03-21","decision":"2024-04-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for Xtandi to include treatment as monotherapy or in combination with androgen deprivation therapy of adult men with high risk biochemical recurrent (BCR) non-metastatic hormone sensitive prostate cancer (nmHSPC) who are unsuitable for salvage radiotherapy, based on final results from study MDV3100-13 (EMBARK); this is a phase 3, randomized, efficacy and safety study of enzalutamide plus leuprolide, enzalutamide monotherapy, and placebo plus leuprolide in men with high-risk nonmetastatic prostate cancer progressing after definitive therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0058","type":"II","opinion":"2022-03-17","decision":"2023-03-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of section 4.5 in order to add information regarding drug-drug interaction based on final results from study 9785-CL-0018 - A Phase 1 Open-label Study to Evaluate the Effect of Multiple Doses of Enzalutamide on the Pharmacokinetics of Substrates of P-glycoprotein (Digoxin) and Breast Cancer Resistant Protein (Rosuvastatin) in Male Subjects with Prostate Cancer. Additionally, the MAH has taken the opportunity to make an update to the information about the excipients in Section 4.4 of the SmPC, to introduce editorial changes in the SmPC and in the Package Leaflet, and to update the list of local representatives in the Package Leaflet."}, {"id":"II/0057","type":"II","opinion":"2022-03-10","decision":"2023-03-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC in order to reflect the updated safety and efficacy data from the final analysis of the 9785-CCL-0335 (ARCHES) study, a phase 3 randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of enzalutamide plus androgen deprivation therapy (ADT) vs. placebo plus ADT in men with mHSPC; the Package Leaflet is updated accordingly."}, {"id":"IB/0061","type":"IB","opinion":"2022-05-24","decision":"2023-03-06","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0060","type":"IAIN","opinion":"2022-05-04","decision":"2023-03-06","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0050","type":"II","opinion":"2021-03-04","decision":"2021-04-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a warning on severe cutaneous adverse reactions based on a safety review; the Package Leaflet is updated accordingly"}, {"id":"II/0049","type":"II","opinion":"2021-01-28","decision":"2021-04-30","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.7","4.8","5.1","5.2"],"scope":"Update of sections 4.4, 4.7, 4.8, 5.1, 5.2 and 5,3 of the SmPC in order to update efficacy and safety information and include a warning on the risk of second primary malignancies based on final results from study MDV3100-14 (PROSPER) listed as a PAES in the Annex II; this is a phase 3, randomized, double-blind, placebo-controlled, efficacy and safety study of enzalutamide in patients with nonmetastatic castration-resistant prostate cancer; the Package Leaflet and Annex II are updated accordingly. The RMP version 15.0 is approved."}, {"id":"II/0047/G","type":"II","opinion":"2021-03-25","decision":"2021-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a","C.I.4"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.7","5.1","6.6"],"scope":"Extension of Indication to include the treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) for Xtandi in combination with androgen deprivation therapy based on the data of study 9785-CL-0335 (ARCHES). As a consequence, sections 4.1, 4.2, 5.1, and 6.6 of the SmPC are updated. Furthermore the MAH took the opportunity to make corrections to section 4.7. The Package Leaflet is updated in accordance. The RMP version 13.0 is approved."}, {"id":"IB/0048","type":"IB","opinion":"2020-02-14","decision":"2021-02-04","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0039/G","type":"II","opinion":"2018-09-20","decision":"2018-10-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication to include adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC) The Package Leaflet is updated in accordance. Update of SmPC to amend the warning on possible association with seizure, to amend the effects on driving or operating machines, to amend the identified adverse reactions and to amend the ‘Race’ subsection regarding pharmacokinetic properties based on the results from the completed studies PROSPER (Phase 3 Randomized Controlled Study) and Asian PREVAIL (Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study) and the updated integrated clinical safety database."}, {"id":"R/0037","type":"R","opinion":"2017-12-14","decision":"2018-02-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"X/0029","type":"X","opinion":"2017-07-20","decision":"2017-09-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"II/0036","type":"II","opinion":"2017-03-09","decision":"2017-09-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC to reflect the final results of study AE-7592-G, “Transfer of Radioactivity into Fetuses and Breast Milk in Rats after a Single Oral Administration of [14C] MDV3100-ISN: 9785-ME-0046”. The Package Leaflet is updated accordingly. The RMP version 11.0 has also been submitted."}, {"id":"II/0035","type":"II","opinion":"2017-06-09","decision":"2017-09-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to reflect the final results of the post authorisation safety study (PASS) CL-9785-0403 which evaluated the risk of seizure among subjects with mCRPC treated with enzalutamide who were at potential increased risk of seizure (UPWARD) and was listed as a category 3 in the RMP. The RMP version 11.0 has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to make a correction in section 5.1 of the SmPC."}, {"id":"II/0034","type":"II","opinion":"2017-05-18","decision":"2017-09-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect relevant information for physicians namely on the observed differences in treatment effect based on prior chemotherapy treatment history. In addition, the MAH took this opportunity to reflect the ATC code for enzalutamide. The RMP version 11.0 has also been submitted."}, {"id":"II/0028/G","type":"II","opinion":"2016-04-01","decision":"2016-12-12","affects":["SmPC","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC based on the results of study 9785-CL-0222 (TERRAIN); an active-controlled study, which evaluated the safety and efficacy of enzalutamide vs bicalutamide in men with metastatic CRPC. The Package Leaflet has been updated accordingly. Further, the MAH provides supportive data from study MDV3100-09 (STRIVE), a second phase 2 study of enzalutamide vs bicalutamide."}, {"id":"II/0026","type":"II","opinion":"2015-12-17","decision":"2016-12-12","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"PSUSA/00010095/201502","type":"PSUSA","opinion":"2015-09-24","decision":"2015-11-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - enzalutamide"}, {"id":"II/0020/G","type":"II","opinion":"2015-09-17","decision":"2015-11-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update information on drug-drug interactions after analysis of studies 9785-CL-0405 and 9785-CL-0406. The Package Leaflet is updated accordingly."}, {"id":"II/0018","type":"II","opinion":"2015-04-23","decision":"2015-06-22","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the Pharmacodynamic properties information regarding Overall Survival (OS) after analysis of data from the PREVAIL (MDV3100-03) study satisfying part of the Obligation to conduct post-authorisation measures as reported in the annex II. The annex II is updated accordingly."}, {"id":"II/0015","type":"II","opinion":"2015-05-21","decision":"2015-06-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to update the safety and pharmacokinetic information in hepatic impairment after finalisation of the study 9785-CL-0404."}, {"id":"II/0016","type":"II","opinion":"2015-03-26","decision":"2015-05-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a warning and update the safety information on posterior reversible encephalopathy syndrome (PRES) following analysis of post-marketing case reports. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct typographical and formatting errors in the SmPC."}, {"id":"IB/0014","type":"IB","opinion":"2015-01-16","decision":"2015-05-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"To introduce the changes requested by PRAC and CHMP in September 2014, to add the signals of QT interval prolongation due to long term use for medicinal products for androgen deprivation therapy."}, {"id":"IB/0012/G","type":"IB","opinion":"2014-12-09","decision":"2015-05-27","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0008","type":"II","opinion":"2014-10-23","decision":"2014-11-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. As a consequence, section 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC and the package leaflet have been updated accordingly. Annex II has also been updated to include an obligation to conduct a post-authorisation measure. The MAH also propose to update the contact details of local representatives in the package leaflet."}, {"id":"II/0007/G","type":"II","opinion":"2014-09-25","decision":"2014-11-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4 and 4.5 of the SmPC further to the results of a study investigating the interaction with docetaxel. Section 4.5 of the SmPC is also updated further to results of a study of enzymes induced by Xtandi. Section 5.2 is updated further to the results of a study investigating the transport of the metabolite M2 by BCRP, of a study to assess protein binding displacement between Xtandi and other medicinal products, of two studies investigating the in vitro metabolism of 14C-M2, and of a pharmacokinetic study in Japanese patients."}, {"id":"II/0006/G","type":"II","opinion":"2014-09-25","decision":"2014-11-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the Summary of Product Characteristics further to the results of embryo-foetal development studies in mice and rabbits and repeat dose toxicity studies in dogs."}, {"id":"IB/0010","type":"IB","opinion":"2014-09-17","decision":"2014-11-28","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update section 4.8 with undesirable effects with unknown frequency in the section on musculoskeletal and connective tissue disorders of the SmPC and package leaflet following a recommendation by PRAC. In addition the presentation of the side effects in this section have been updated to the latest QRD template. Furthermore minor corrections to the FR annexes were implemented to bring it in line with the EN annexes."} ] }, "epcoritamab__tepkinly": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tepkinly-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tepkinly-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000325305","type":"IAIN","opinion":"2026-02-06","decision":"2026-07-02","affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL to implement the signal recommendations on 'hypogammaglobulinaemia (EPITT no. 20174)' adopted at the 30 October 2025 PRAC."}, {"id":"EMA/VR/0000311043","type":"II","opinion":"2026-05-21","decision":"2026-07-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with rituximab and lenalidomide treatment of patients with relapsed/refractory follicular lymphoma (FL) for Tepkinly, based on interim results from study M20-638; this is a Phase 3, open-label study to evaluate safety and efficacy of epcoritamab in combination with rituximab and lenalidomide (R2) compared to R2 in subjects with relapsed or refractory follicular lymphoma (EPCORE FL-1). As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 3.2.0 of the RMP has also been submitted."}, {"id":"EMA/VR/0000280386","type":"II","opinion":"2025-12-04","decision":"2026-07-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to modify instructions based on results from study M23-362; this is a Phase 2, open-label study to evaluate adverse events of subcutaneous epcoritamab administered in the outpatient setting in adult participants with R/R DLBCL and classic FL. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor changes to the Product Information."}, {"id":"PSUSA/00000107/202503","type":"PSUSA","opinion":"2025-11-13","decision":"2026-01-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - epcoritamab"}, {"id":"EMA/R/0000257200","type":"R","opinion":"2025-05-22","decision":"2025-07-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation."}, {"id":"PSUSA/00000107/202409","type":"PSUSA","opinion":"2025-04-25","decision":"2025-06-23","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - epcoritamab"}, {"id":"IB/0007","type":"IB","opinion":"2025-01-07","decision":"2025-06-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0006","type":"IB","opinion":"2024-10-25","decision":"2025-06-23","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00000107/202403","type":"PSUSA","opinion":"2024-10-17","decision":"2024-12-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - epcoritamab"}, {"id":"II/0001","type":"II","opinion":"2024-06-27","decision":"2024-08-16","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy for TEPKINLY, based on results from the indolent Non-Hodgkins Lymphoma (iNHL) expansion cohort of Study GCT3013-01, the First In Human (FIH) Phase 1/2 study in R/R B-NHL, with key supportive data from the Phase 1b/2 Study GCT3013-04 in Japanese subjects. Study GCT3013-01 is an ongoing global, single-arm, Phase 1/2 study designed to evaluate epcoritamab as monotherapy in R/R B-NHL. As a consequence, sections 1, 3, 4.1, 4.2, 4.4, 4.8, 5.1, 5.2, 6.3, 6.4, 6.5 and 6.6 of the SmPC are updated."}, {"id":"N/0003","type":"N","opinion":"2024-04-08","decision":"2024-07-17","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "erdafitinib__balversa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/balversa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/balversa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000356661","type":"N","opinion":"2026-06-19","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"EMA/VR/0000340655","type":"IAIN","opinion":"2026-04-24","decision":null,"affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.) - Implementation of the agreed wording"}, {"id":"II/0001","type":"II","opinion":"2024-11-28","decision":"2026-02-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add cataract as a new ADR with frequency common based on a review of new information observed in clinical studies and in the post marketing setting. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of the most common ADRs in the SmPC section 4.8 and to make editorial corrections in the SmPC and Package Leaflet. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"EMA/VR/0000248998","type":"IA","opinion":"2025-02-18","decision":"2026-02-23","affects":["SmPC","Labelling","PL"],"codes":["B.I.b.2.a","B.II.b.5.z","B.II.e.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for active substance or starting material/reagent/intermediate used in the manufacturing process of the active substance - Minor changes to an approved test procedure; Change to in-process tests or limits applied during the manufacture of the finished product - Minor change of an analytical procedure for an in-process control; Change in type of container or addition of a new container - Deletion of an immediate packaging container that does not lead to the complete deletion of a strength or pharmaceutical form"} ] }, "erlotinib__tarceva": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tarceva-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tarceva-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"T/0073","type":"T","opinion":"2024-10-24","decision":"2024-11-14","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0071","type":"II","opinion":"2023-03-16","decision":"2024-03-14","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Change(s) with new additional data submitted by the MAH"}, {"id":"IB/0067","type":"IB","opinion":"2021-02-22","decision":"2022-02-18","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0068","type":"IA","opinion":"2021-07-14","decision":"2022-02-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0060","type":"N","opinion":"2018-08-09","decision":"2019-02-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0058","type":"II","opinion":"2018-11-15","decision":"2019-02-07","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.6","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.5 and 5.1 of the SmPC based on phase III clinical study MO22162 (CURRENTS) comparing a higher dose of Tarceva (300 mg) over the recommended daily dose (150 mg) in current smokers with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the second-line setting after failure of chemotherapy. The Package Leaflet is updated accordingly. The RMP version 7.1 has been agreed, as part of this application. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor editorial changes in sections 4.4, 4.5, 4.6, 4.8, 5.1 and 5.2 of the SmPC."}, {"id":"II/0052","type":"II","opinion":"2018-02-22","decision":"2019-02-07","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.4 of the SmPC in order to include recommendations on Epidermal Growth Factor Receptor (EGFR) mutation status testing, to be in line with current technical and scientific progress. In addition, the Marketing authorisation holder (MAH) took the opportunity to make a minor correction in section 4.2 of the SmPC and minor editorial changes and to bring the PI in line with the latest QRD template version 10. Furthermore, the Annex II has been corrected, as requested by the EMA, to include Educational Material as an additional risk minimisation measure, which are already included in the RMP."}, {"id":"T/0057","type":"T","opinion":"2018-02-20","decision":"2018-04-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0051","type":"II","opinion":"2017-11-09","decision":"2017-12-11","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["4.1"],"scope":"Update of section 4.1 of the SmPC in relation to the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen based on a review of relevant literature, Real World Data Reports (BIOMARQUEURS FRANCE CSR and ESCAP-2011-CPHG CSR) and a new CSR Addendum of the previously submitted relevant pivotal study BR.21, as requested by the CHMP following assessment of variation EMEA/H/C/000618/II/0043"}, {"id":"N/0047","type":"N","opinion":"2016-07-21","decision":"2017-10-30","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0048","type":"IB","opinion":"2016-11-12","decision":"2017-10-30","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"II/0043","type":"II","opinion":"2015-12-17","decision":"2016-01-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Modification of the indication to limit maintenance treatment to NSCLC patients with an EGFR-activating mutation and stable disease after first-line chemotherapy based on the data from study BO25460 (IUNO). Consequently, SmPC sections 4.1, 4.8 and 5.1 have been updated. The Package leaflet is updated accordingly."}, {"id":"II/0033","type":"II","opinion":"2013-12-18","decision":"2014-10-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add the adverse reaction uveitis with a frequency very rare. The Package Leaflet was updated accordingly. Minor editorial or typographical corrections have been implemented throughout the PI."}, {"id":"II/0032","type":"II","opinion":"2013-10-24","decision":"2014-10-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include updated efficacy results from study ML20650 (EURTAC) of erlotinib in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) - activating mutations."}, {"id":"II/0031","type":"II","opinion":"2013-02-21","decision":"2013-08-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include the adverse reaction Palmar-Plantar Erythrodysaesthesia Syndrome (PPES) as requested by the PRAC. The Package Leaflet has been updated accordingly. Furthermore, the PI has been brought in line with the latest QRD template version 8.3. The requested variation proposed amendments to the Summary of Product Characteristics, Annex II and Package Leaflet."}, {"id":"IAIN/0028/G","type":"IAIN","opinion":"2012-09-27","decision":"2012-10-29","affects":["SmPC","PL"],"codes":["B.II.a.1.a","A.7","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings; Administrative change - Deletion of manufacturing sites; Change to batch release arrangements and quality control testing of the FP - Replacement or addition of a site where batch control/testing takes place"}, {"id":"II/0027","type":"II","opinion":"2012-05-24","decision":"2012-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add the adverse reactions folliculitis and acne/dermatitis acneiform further to a review of infections in skin, subcutaneous tissue and mucosa performed by the MAH at the request of the CHMP in the assessment of the renewal. The Package Leaflet was updated accordingly. The MAH also took the opportunity to update the product information in line with QRD template version 8.1."}, {"id":"II/0020","type":"II","opinion":"2011-07-21","decision":"2011-08-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.4"],"scope":"Extension of indication of Tarceva for the first-line treatment of locally advanced or metastatic NSCLC with EGFR activating mutations. The MAH also applied to revise the warnings on keratitis in section 4.4 of the SmPC and sections 2, 4 of the Package Leaflet following a request from the CHMP to harmonise the wording across EGFR inhibitor products. Annex II has also been updated to reflect the latest Risk Management Plan version number (RMP v. 3.1). The MAH took the opportunity to introduce amendments to the list of local representatives in the Package Leaflet."}, {"id":"II/0026","type":"II","opinion":"2011-04-14","decision":"2011-05-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC following the completion of the 2 year carcinogenicity studies conducted with erlotinib in rats and mice. In addition to this, further to the assessment of FUM 32 (user testing) the MAH took the opportunity to include some minor layout changes to the sections 2 and 4 of the PL."}, {"id":"IB/0021","type":"IB","opinion":"2010-08-12","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"R/0018","type":"R","opinion":"2010-04-22","decision":"2010-07-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0019/G","type":"II","opinion":"2010-05-20","decision":"2010-07-01","affects":["SmPC","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of section 4.5 of the Summary of Product Characteristics (SmPC) to revise the wording of the interaction with coumarins-derivative anticoagulants and to include interaction with statins. In addition to this, sections 4.4 and 4.8 of the SmPC have been updated to include fatal diarrhoea. All the above changes were requested further to the assessment of the 6th PSUR. The Package Leaflet has been updated accordingly. Furthermore, sections 4.4 and 4.8 of the SmPC have been updated in order to include the fatal outcome of cases with gastrointensinal perforation based on a safety review conducted by the MAH. In addition, section 4.8 of the SmPC has been updated to include skin fissures."}, {"id":"II/0017","type":"II","opinion":"2010-03-18","decision":"2010-04-27","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of the indication for use as monotherapy for maintenance treatment in patients with locally advanced or metastatic non-small cell lung cancer with stable disease after 4 cycles of standard platinum-based first-line chemotherapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SPC have been updated. The Package Leaflet has been updated accordingly. Furthermore, Annex II has been updated in order to include the agreed Risk Management Plan."}, {"id":"II/0016","type":"II","opinion":"2009-04-23","decision":"2009-05-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update to sections 4.4 (special warnings and precautions for use) and 4.8 (undesirable effects) of the SPC with new safety information on corneal perforation, GI perforation and serious skin conditions. The Package Leaflet has been updated accordingly. The contact details of the Latvian local representative has also been updated in the Package Leaflet."}, {"id":"II/0014","type":"II","opinion":"2008-12-18","decision":"2009-01-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.1"],"scope":"Update of section 4.2, 4.5 and 5.1 of the SPC with the results of studies BP21502 (interaction with ranitidine) and OSI-774-107, (PK in smokers) which were part of the follow-up measures and addition of the term alveolitis under section 4.4 of the SPC as requested from the CHMP following the latest PSUR assessment."}, {"id":"II/0012","type":"II","opinion":"2007-12-13","decision":"2008-01-18","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.2"],"scope":"Update of section 4.2 and 5.2 of the SPC with information on the use of Tarceva in patients with hepatic impairment and amendment of section 4.8 of the SPC with updated information on adverse events. The package leaflet has been revised accordingly. The MAH has also applied to amend the Labelling with the information given in Braille and to make several editorial changes to the Package Leaflet to improve readability as well as to update the contact details in the list of local representatives for Estonia and Finland."}, {"id":"IA/0011","type":"IA","opinion":"2007-09-21","decision":null,"affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change/addition of imprints, bossing or other markings"}, {"id":"II/0010","type":"II","opinion":"2007-06-21","decision":"2007-07-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5","5.1"],"scope":"Update of section 4.5 of the SPC with information on the interactions with omeprazole and ciprofloxacin. The Package Leaflet has also been updated accordingly. In addition, the new ATC code was implemented in section 5.1 of the SPC."}, {"id":"II/0008","type":"II","opinion":"2007-01-24","decision":"2007-02-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The Marketing Authorisation Holder (MAH) has applied for a type II variation, upon request by the CHMP following the assessment of the 3rd Periodic Safety Update Report (PSUR), to update section 4.4 of the SPC with clarification on events of dehydration, and section 4.8 of the SPC with information regarding severe infections and the adverse drug reactions (ADRs) 'dehydration', 'hypokaliemia', 'renal failure', 'alopecia' and 'dermatitis acneiform'. Furthermore, sections 4.4 and 4.8 of the SPC and section 4 of the Package Leaflet were also updated with information on hepatic failure. In addition, the MAH made minor editorial changes to the SPC and Package Leaflet."}, {"id":"II/0007","type":"II","opinion":"2007-01-24","decision":"2007-02-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"The Marketing Authorisation Holder (MAH) applied for a type II variation, upon request by the CHMP following the assessment of a follow-up measure (FUM 008), to update section 4.5 of the Summary of Product Characteristics (SPC) to reflect the results of interaction studies of erlotinib with capecitabine, carboplatin/paclitaxel CYP3A4 substrates rifampicin. The Package Leaflet has been updated accordingly."}, {"id":"II/0002","type":"II","opinion":"2006-12-14","decision":"2007-01-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"This is an extension of the indication of Tarceva (erlotinib hydrochloride) in combination with gemcitabine in first-line treatment of patients with metastatic pancreatic cancer. When prescribing Tarceva, factors associated with prolonged survival should be taken into account. No survival advanatage could be shown for patients with locally advanced disease."}, {"id":"IA/0009","type":"IA","opinion":"2006-12-01","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0006","type":"II","opinion":"2006-10-18","decision":"2006-11-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8","5.2"],"scope":"Update of the SPC sections 4.4, 4.5 and 5.2 with the results of the final report of a clinical interaction study evaluating the effect of smoking on erlotinib pharmacokinetics. The Package Leaflet has also been updated accordingly. In addition an amendment to section 4.8 was introduced. The MAH has also taken the opportunity to update the annexes according to the latest QRD template"}, {"id":"II/0003","type":"II","opinion":"2006-02-23","decision":"2006-03-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"The MAH applied to update section 4.4 of the SPC and accordingly sections 2 and 4 of the Package Leaflet with information on secondary effects of severe diarrhoea; dehydration, hypokaleamia and acute renal failure"}, {"id":"IA/0001","type":"IA","opinion":"2005-10-10","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"} ] }, "everolimus__afinitor": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/afinitor-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/afinitor-epar-procedural-steps-taken-scientific-information-after-authorisation-archived_en.pdf"], "procedures": [ {"id":"IAIN/0092","type":"IAIN","opinion":"2024-11-21","decision":"2026-02-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000310437","type":"IA","opinion":"2025-11-20","decision":null,"affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000291874","type":"IAIN","opinion":"2025-08-25","decision":null,"affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"IG/1520","type":"IG","opinion":"2022-06-24","decision":"2023-09-15","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IG/1518","type":"IG","opinion":"2022-06-24","decision":"2023-09-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/1995","type":"WS","opinion":"2021-05-20","decision":"2022-06-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.7"],"scope":"Update of the Afinitor and Votubia SmPCs to include radiation recall syndrome as an adverse drug reaction observed in the post-marketing phase with unknown frequency (Section 4.8) and a cautionary text regarding radiation therpay complications in ‘Special warnings and precautions for use’ (Section 4.4). Corresponding changes are also made to the SmPC section 4.5 and package leaflets."}, {"id":"N/0077","type":"N","opinion":"2021-10-12","decision":"2022-06-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0076","type":"II","opinion":"2021-10-28","decision":"2022-06-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the SmPC section 4.8 to include Lymphoedema as an adverse drug reaction with the frequency common based on the post-marketing data as requested by the PRAC. The PL is updated accordingly."}, {"id":"II/0073","type":"II","opinion":"2021-09-16","decision":"2022-06-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the SmPC section 5.1 based on the results of the analysis of final progression free and overall survival (OS) for study CRAD001T2302."}, {"id":"IAIN/0071/G","type":"IAIN","opinion":"2021-05-27","decision":"2022-06-13","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement of a manufacturer responsible for importation and/or batch release."}, {"id":"IB/0067/G","type":"IB","opinion":"2020-06-09","decision":"2021-07-23","affects":["SmPC"],"codes":["B.II.d.1.a","B.II.d.1.c","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Tightening of specification limits; Change in the specification parameters and/or limits of the finished product - Addition of a new specification parameter to the specification with its corresponding test method; Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"IAIN/0066/G","type":"IAIN","opinion":"2020-02-13","decision":"2021-07-23","affects":["Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Deletion of manufacturing sites; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0060","type":"R","opinion":"2019-01-31","decision":"2019-04-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0058","type":"II","opinion":"2018-09-20","decision":"2019-04-02","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to add new safety and efficacy information based on the final report from study CRAD001Y2201, listed as a category 1 study in the RMP. This was a three arm randomised study investigating the combination of everolimus with exemestane versus everolimus alone versus capecitabine in patients with oestrogen receptor positive metastatic breast cancer after recurrence or progression on letrozole or anastrozole. As a consequence of the study completion, Annex II of the Product Information was updated to remove this study."}, {"id":"WS/1160","type":"WS","opinion":"2017-05-18","decision":"2018-05-08","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"WS/1144/G","type":"WS","opinion":"2017-06-29","decision":"2018-05-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to include new safety information on stomatitis and its management based on final results from study CRAD001JUS226: a phase II, single arm study of the use of steroid-based mouthwash to prevent stomatitis in postmenopausal women with advanced or metastatic hormone receptor positive breast cancer being treated with everolimus plus exemestane Update of section 4.6 of the SmPC in order to add new information on breast-feeding based on pre-clinical data. The Package Leaflets were updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to bring the Afinitor PI in line with the latest QRD template version 10."}, {"id":"T/0057","type":"T","opinion":"2018-03-26","decision":"2018-05-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0048","type":"II","opinion":"2016-04-28","decision":"2016-05-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of Indication to include a new indication for the treatment of unresectable or metastatic, well-differentiated non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease; as a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Furthermore, the PI is brought in line with the latest QRD template version 9.1."}, {"id":"II/0043/G","type":"II","opinion":"2015-02-26","decision":"2016-02-24","affects":["SmPC","Labelling","PL"],"codes":["A.1","C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Afinitor SmPC with final overall survival results for Study CRAD001C2324 (RADIANT-3); in addition, an administrative change in the address of the MAH has been also included in the grouped procedure."}, {"id":"PSUV/0039","type":"PSUV","opinion":"2014-10-23","decision":"2014-12-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0041","type":"II","opinion":"2014-10-23","decision":"2014-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"This variation concerns the update of the pooled safety data in section 4.8 of the SmPC in line with the revised Core Data Sheet following a review of the expanded safety data from a total of 9 studies related to the approved oncology indications. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to add a sentence to section 4.8 of the SmPC to clarify that angioedema has been reported with and without concomitant use of ACE inhibitors."}, {"id":"II/0038","type":"II","opinion":"2014-09-25","decision":"2014-12-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"R/0036","type":"R","opinion":"2014-03-20","decision":"2014-05-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0033","type":"II","opinion":"2013-07-25","decision":"2014-05-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to clarify the dose adjustments for hepatic impaired patients based on the results of two studies X2102 and A2303."}, {"id":"II/0032","type":"II","opinion":"2013-10-24","decision":"2014-05-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update the safety information on the interaction of Afinitor with moderate CYP3A4/PgP inhibitors. The requested variation proposed amendments to the Summary of Product Characteristics."}, {"id":"II/0031","type":"II","opinion":"2013-07-25","decision":"2014-05-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC with information related to the female fertility based on the clinical and nonclinical experience with Afinitor. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet with the addition of the Croatian representative and to amend contact details for the representative of the Netherlands. Furthermore, the PI is being brought in line with the latest QRD template version 9.0. The requested variation proposed amendments to the Summary of Product Characteristics, Annex II and Package Leaflet."}, {"id":"II/0030","type":"II","opinion":"2013-11-21","decision":"2014-05-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SmPC based on the pooled safety database from eight clinical studies. A specific subsection for older people has also been introduced. Consequential changes have been introduced in section 4.4 of the SmPC. The PL was updated accordingly. In addition, the MAH took the opportunity to make an administrative change in section 5 of the PL. Furthermore, the MAH took this opportunity to bring the PI in line with the latest QRD template version 9. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"IAIN/0034","type":"IAIN","opinion":"2013-10-22","decision":"2014-05-16","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"II/0023/G","type":"II","opinion":"2013-04-25","decision":"2013-05-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8"],"scope":"Update of sections 4.2 and 4.4 of the SmPC with additional clarification on dose recommendations to manage the most commonly occurring adverse events. In addition, sections 4.6 and 4.8 in the SmPC have been updated to include information on amenorrhea. The Package Leaflet was updated accordingly. Furthermore, the MAH took the opportunity to make minor changes to the SmPC. Finally, the PI is being brought in line with the latest QRD template version 8.3."}, {"id":"X/0017/G","type":"X","opinion":"2012-10-18","decision":"2012-12-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2","6.4"],"scope":"Update of the Product Information (PI) for Afinitor based on the results of study X2102 in hepatically impaired patients and to apply for a new dosage strength of Afinitor 2.5 mg tablets to accommodate for the revised dosing recommendations in such patients. Sections 4.2, 4.4 and 5.2 of the SmPC were updated and the package leaflet was updated accordingly. Section 6.4 of the SmPC, Labelling and Package Leaflet were also updated regarding storage conditions. In addition, the MAH took the opportunity to make minor editorial amendments in the SmPC and to update the list of local representatives in the Package Leaflet. Furthermore, the PI is brought in line with the latest QRD template version 8."}, {"id":"II/0020","type":"II","opinion":"2012-06-21","decision":"2012-07-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.5","4.6","4.8","5.1","5.3"],"scope":"Extension of indication to include Afinitor for the treatment of hormone receptor-positive, HER2/neu negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. Consequently the sections 4.1, 4.5, 4.8 and 5.1 of the SmPC were updated in order to include changes in the indication. Section 4.6 was updated to align with wording in the SmPC for Votubia and minor editorial changes were made to section 5.3 to revise the wording to correlate exposure in rats in a male fertility study and clinical exposure. The Package Leaflet is updated accordingly."}, {"id":"II/0015","type":"II","opinion":"2012-02-16","decision":"2012-03-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"The scope of this type II variation is to amend the product information for Afinitor based on the results of study X2301 with an update of sections 4.4 and 4.5 of the SmPC to revise the information on the precaution for administration of Afinitor in combination with oral CYP3A4 substrates and update of the information on interaction of everolimus with CYP3A4, respectively. There were no changes to the Package Leaflet."}, {"id":"II/0014","type":"II","opinion":"2011-10-20","decision":"2011-11-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update the product information for Afinitor with Deep Vein Thrombosis (DVT) as an adverse drug reaction. Changes are as follows: to include deep vein thrombosis as an uncommon adverse drug reaction in section 4.8 of the Summary of Product Characteristics (SmPC) and as an uncommon side effect in Section 4 of the Package Leaflet (PL)."}, {"id":"II/0008","type":"II","opinion":"2011-07-21","decision":"2011-08-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.5","4.8","5.1"],"scope":"Extension of indication Extension of indication to include 'Afinitor is indicated for the treatment of unresectable or metastatic, well-or moderately-differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease'. Consequently, sections 4.1, 4.4, 4.5, 4.8 and 5.1 of the Summary of Product Characteristics and the Package Leaflet have been updated. The Risk Management Plan statement in Annex II has been updated to the new template. The MAH also took the opportunity to update the product information in line with the QRD template (version 7.3.1) and to make minor corrections."}, {"id":"II/0009/G","type":"II","opinion":"2011-04-14","decision":"2011-06-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Variations related to significant modifications of the SPC due in particular to new quality, pre-clinical, clinical or pharmacovigilance data"}, {"id":"IG/0032/G","type":"IG","opinion":"2010-12-21","decision":null,"affects":["Annex II"],"codes":["C.I.9.c","C.I.9.e","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the Detailed Description of the Pharmacovigilance System (DDPS) to version 9.0, to include: - a change in the deputy of the Qualified Person for Pharmacovigilance (QPPV); - a change in the major contractual arrangements. - administrative changes not impacting the operation of the pharmacovigilance system. Annex II.B has also been updated with the latest wording as per October 2010 CHMP procedural announcement."}, {"id":"II/0005","type":"II","opinion":"2010-03-18","decision":"2010-04-27","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Within the finished product specifiction: to raise the authorised content limit for an already identified degradation product and to add a test parameter specification for a newly identified degradation product; finished product shelf life is updated accordingly based on the initially registered stability data. Opportunity is taken to submit updated validation reports."}, {"id":"II/0006","type":"II","opinion":"2010-02-18","decision":"2010-03-30","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) to include information regarding reported cases of hepatitis B reactivation based on the review of a signal prompted by a fatal outcome during an ongoing clinical study. The Package Leaflet has been updated accordingly. Section 4.5 of the SmPC has been updated to include corticosteroids as a drug class of the CYP3A4 inducers. In section 4.4 of the SmPC, a sentence regarding the occurrence of hyperglycaemia in patients who had abnormal fasting glucose was removed based on data from the pivotal phase 3 trial C2240. Frequencies of adverse events have been corrected in the PL in line with the SmPC."}, {"id":"II/0004","type":"II","opinion":"2010-02-18","decision":"2010-03-30","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance system (DDPS) to version 8.0, including a change of the Qualified Person for Pharmacovigilance (QPPV). Consequently, Annex II has been updated with the new version number of the agreed DDPS."}, {"id":"IB/0002","type":"IB","opinion":"2009-10-15","decision":"2009-10-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units outside range of appr. pack size"}, {"id":"IB/0001","type":"IB","opinion":"2009-10-15","decision":"2009-10-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units outside range of appr. pack size"} ] }, "everolimus__votubia": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/votubia-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/votubia-epar-procedural-steps-taken-scientific-information-after-authorisation-archived_en.pdf"], "procedures": [ {"id":"EMA/VR/0000310311","type":"IA","opinion":"2025-11-21","decision":null,"affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000292327","type":"IAIN","opinion":"2025-08-20","decision":null,"affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"IAIN/0090","type":"IAIN","opinion":"2024-12-04","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IG/1520","type":"IG","opinion":"2022-06-24","decision":"2023-06-19","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IG/1518","type":"IG","opinion":"2022-06-24","decision":"2023-06-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/1995","type":"WS","opinion":"2021-05-20","decision":"2022-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.7"],"scope":"Update of the Afinitor and Votubia SmPCs to include radiation recall syndrome as an adverse drug reaction observed in the post-marketing phase with unknown frequency (Section 4.8) and a cautionary text regarding radiation therpay complications in ‘Special warnings and precautions for use’ (Section 4.4). Corresponding changes are also made to the SmPC section 4.5 and package leaflets."}, {"id":"N/0073","type":"N","opinion":"2021-10-12","decision":"2022-06-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0070/G","type":"IAIN","opinion":"2021-06-03","decision":"2022-06-21","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0061","type":"II","opinion":"2020-07-23","decision":"2020-08-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1, and 5.2 of the SmPC based on results from a modelling and simulation study of patients from 6 months to less than 2 years of age whose refractory partial-onset seizures, with or without secondary generalisation, are associated with tuberous sclerosis complex. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1."}, {"id":"R/0065","type":"R","opinion":"2020-05-28","decision":"2020-07-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0064/G","type":"IAIN","opinion":"2020-01-22","decision":"2020-07-23","affects":["Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Site Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0051","type":"II","opinion":"2018-07-12","decision":"2019-06-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of sections 4.8 (all pharmaceutical forms) and 5.1 (dispersible tablets only) of the SmPC in order to update the safety and efficacy information based on final results from study CRAD001M2304, listed as a category 3 study in the RMP; this is a three-arm, randomized, double-blind, placebo-controlled study of the efficacy and safety of two trough-ranges of everolimus as adjunctive therapy in patients with tuberous sclerosis complex (TSC) who have refractory partial-onset seizures. The Package Leaflet is updated accordingly."}, {"id":"T/0052","type":"T","opinion":"2018-05-16","decision":"2018-06-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"X/0045","type":"X","opinion":"2018-03-22","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"WS/1160","type":"WS","opinion":"2017-05-18","decision":"2018-05-31","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"WS/1144/G","type":"WS","opinion":"2017-06-29","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to include new safety information on stomatitis and its management based on final results from study CRAD001JUS226: a phase II, single arm study of the use of steroid-based mouthwash to prevent stomatitis in postmenopausal women with advanced or metastatic hormone receptor positive breast cancer being treated with everolimus plus exemestane Update of section 4.6 of the SmPC in order to add new information on breast-feeding based on pre-clinical data. The Package Leaflets were updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to bring the Afinitor PI in line with the latest QRD template version 10."}, {"id":"IB/0047/G","type":"IB","opinion":"2017-10-16","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1","B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"II/0044","type":"II","opinion":"2017-06-22","decision":"2017-07-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC for Votubia 2.5 mg, 5 mg and 10 mg tablets and 2 mg, 3 mg and 5 mg dispersible tablets in order to reflect on data from study CRAD001M2304, in particular to revise dosing recommendations for patients with hepatic impairment, to update the warning related to infections, to include “sepsis” as an adverse drug reaction with the frequency “uncommon” and to revise frequencies of the following adverse drug reactions: “pharyngitis” [“common” to “very common”], “pneumonitis” [“uncommon” to “common”] and “rash” [“common” to “very common]”."}, {"id":"II/0041","type":"II","opinion":"2016-12-15","decision":"2017-01-27","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include adjunctive treatment of patients aged 2 years and older with refractory seizures associated with tuberous sclerosis complex (TSC) for Votubia 2 mg, 3 mg and 5 mg dispersible tablets. Sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC were updated in parallel based on the results from the pivotal study. In addition, sections 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 were also updated for the 2.5 mg, 5 mg and 10 mg tablets to reflect on data relevant to these formulations. The Package Leaflet was updated in accordance. Furthermore, the PI was brought in line with the latest QRD template version 10."}, {"id":"II/0039","type":"II","opinion":"2016-02-25","decision":"2017-01-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2 and 4.8 (for dispersible tablets) and sections 4.2, 4.8 and 5.1 (for tablets) of the SmPC in order to update the safety and efficacy information with the data from the final CSR comprising the extension phase of study M2302 in fulfilment of PAM (ANX 027). The Annex II and Package Leaflet are updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor editorial changes in the SmPC and to make few updates in the PI in order to align with Afinitor PI. Furthermore, the MAH took the opportunity to bring the PI in line with the latest QRD template version 9.1. Moreover, the revised RMP version 11.0 has been submitted."}, {"id":"II/0038","type":"II","opinion":"2015-10-22","decision":"2015-12-10","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to define an appropriate initial dose for patients below the age of 3 years following requested additional simulations and Literature searches analysis. The Package Leaflet is updated accordingly."}, {"id":"II/0034","type":"II","opinion":"2015-09-24","decision":"2015-11-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to update product information after completion of long-term follow up on duration of responses and time to progression for study M2301. The Package Leaflet is updated accordingly. The data submitted fulfils the specific obligation SOB 024 and the Conditional Marketing Authorisation is switched to a Marketing Authorisation not subject to specific obligations. Votubia is also removed from the European list of additionally monitored medicines."}, {"id":"II/0030/G","type":"II","opinion":"2015-02-26","decision":"2015-07-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of SmPC section 5.2 to provide information regarding the effect of food on the pharmacokinetics of the Votubia dispersible tablets based on Study X2114. Further, the MAH took the opportunity to implement editorial changes in the SmPC. Update of SmPC section 4.5 to provide a recommendation to consider a washout period following discontinuation of concomitant moderate CYP3A4/PgP inhibitors and potent CYP3A4 inducers, and to align the corticosteroid inducer-classification with the approved Afinitor SmPC (pursuant to variation II-32)"}, {"id":"IAIN/0032","type":"IAIN","opinion":"2015-02-10","decision":"2015-07-28","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUV/0025","type":"PSUV","opinion":"2014-10-23","decision":"2014-12-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0028","type":"II","opinion":"2014-10-23","decision":"2014-12-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the efficacy data in section 5.1 of the SmPC (5-year analysis) based on the CSR for study CRAD001C2485, an open-label study of everolimus in patients with SEGA associated with TSC. The CSR is provided in accordance with Article 46 and is part of the post-authorisation measure ANX 016."}, {"id":"II/0027","type":"II","opinion":"2014-09-25","decision":"2014-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the pooled safety data in section 4.8 of the SmPC in line with the revised Core Data Sheet following a review of the safety data from studies CRAD001M2301, CRAD001M2302 and CRAD001C2485. The Package Leaflet has been updated accordingly."}, {"id":"II/0020","type":"II","opinion":"2014-06-26","decision":"2014-12-16","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC further to the pharmacokinetic sub-study results from the pivotal trial CRAD001M2301 investigating the pharmacokinetics in the paediatric population (MEA 017)."}, {"id":"R/0024","type":"R","opinion":"2014-05-22","decision":"2014-07-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUV/0022","type":"PSUV","opinion":"2014-04-25","decision":"2014-06-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0019","type":"II","opinion":"2013-11-21","decision":"2014-06-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of Section 5.2 of the SmPC to clarify that the dose adjustments for hepatic impairment patients was based on results of two studies conducted in patients with impaired hepatic function relative to subjects with normal hepatic function. The requested variation proposed amendments to the Summary of Product Characteristics."}, {"id":"X/0008/G","type":"X","opinion":"2013-09-19","decision":"2013-11-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include treatment of patients < 3 years of age with TSC who have SEGA. In addition, the SmPC was updated based on efficacy and safety data from the pivotal Study M2301 and longer-term follow-up from the Study C2485 for the SEGA paediatric population. A revised starting dose from 3 mg/m2 to 4.5 mg/m2 for patients with TSC who have SEGA has also been included. The SmPC was modified in sections 2, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.8, 5.1 and 5.2. The Package Leaflet and Labelling were updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"N/0018","type":"N","opinion":"2013-08-07","decision":"2013-11-15","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0016/G","type":"II","opinion":"2013-09-19","decision":"2013-11-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.6","4.8","5.3"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with the pooled safety data based on three studies (CRAD001C2485, CRAD001M2301, CRAD001M2302), update of sections 4.6 and 5.3 of the SmPC with information related to female fertility based on the clinical and nonclinical experience with everolimus and update of sections 4.4 and 4.5 of the SmPC with regard to the potential interaction of Votubia with CYP3A4/5 substrates based on the results of X2103 study. In addition, the MAH took the opportunity to propose minor further changes to the SmPC. The package Leaflet was updated accordingly. The requested group of variations proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"R/0015","type":"R","opinion":"2013-04-25","decision":"2013-07-17","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0012","type":"IB","opinion":"2012-12-19","decision":"2013-07-15","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"II/0004","type":"II","opinion":"2012-09-20","decision":"2012-10-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include Votubia for the treatment of “adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but who do not require immediate surgery. The evidence is based on analysis of change in sum of angiomyolipoma volume.”Consequently the sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 5.1, 5.2 and 6.6 of the SmPC were updated in order to include changes related to the indication. The Package Leaflet was updated accordingly. The requested variation proposed amendments to the SmPC and Package Leaflet."}, {"id":"R/0005","type":"R","opinion":"2012-05-24","decision":"2012-07-26","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0002","type":"II","opinion":"2012-05-24","decision":"2012-06-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4, and 5.2 of the SmPC in order to update the safety information based on the results of study CRAD001X2102 which investigated the effect of everolimus in hepatically impaired patients (Child Pugh A-C) and dose adjustment according to grade. Section 4.2 was updated to include dosing recommendations for hepatically impaired patients, section 4.4 to advise on the precaution of the administration of Votubia in hepatically impaired patients, and section 5.2 to include the key results of the pharmacokinetic study of everolimus in subjects with impaired hepatic function. No changes have been proposed for the Package Leaflet."}, {"id":"II/0001","type":"II","opinion":"2011-12-15","decision":"2012-02-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update the product information for Votubia with Deep Vein Thrombosis (DVT) as an adverse drug reaction. Changes are as follows: to include deep vein thrombosis as an uncommon adverse drug reaction in section 4.8 of the Summary of Product Characteristics (SmPC) and as an uncommon side effect in Section 4 of the Package Leaflet (PL)."} ] }, "fedratinib__inrebic": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/inrebic-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/inrebic-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000324950","type":"II","opinion":"2026-07-23","decision":null,"affects":["SmPC","PL"],"codes":["C.4","C.3.c"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"A grouped application consisting of: Update of sections 4.4, 4.8, and 5.1 of the SmPC in order to update clinical pharmacology, efficacy and safety information based on final results from study FEDR MF 002 listed as a category 3 study in the RMP; this is a phase 3, multicentre, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy in subjects with dipss-intermediate or high-risk primary myelofibrosis, post-polycythaemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis and previously treated with ruxolitinib; the Package Leaflet is updated accordingly. The RMP version 4.1 has also been submitted."}, {"id":"II/0026","type":"II","opinion":"2025-06-05","decision":"2025-12-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a warning regarding 'Uveitis' and to add this to the list of adverse drug reactions (ADRs) with frequency 'common' based on a cumulative safety review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"EMA/R/0000264185","type":"R","opinion":"2025-10-16","decision":"2025-12-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0020","type":"II","opinion":"2025-01-30","decision":"2025-02-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to update information regarding thiamine levels based on a review of the primary results of the study FEDR-MF-002. This is a Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared with BAT in subjects with DIPSS intermediate-2 or high-risk primary MF, post-PV MF, or post-ET MF and previously treated with ruxolitinib. The Package Leaflet has been updated accordingly and also to amend the list of local representatives. The RMP (version 3.1) has also been updated."}, {"id":"II/0019","type":"II","opinion":"2024-05-30","decision":"2024-07-05","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update posology recommendations in patients with severe hepatic impairment and to update pharmacokinetic information based on final results from study FEDR-CP-001 listed as a category 3 study in the RMP; this is a phase 1, open-label, single-dose study to assess the pharmacokinetics, safety, and tolerability of fedratinib in subjects with moderate and severe hepatic impairment compared with healthy subjects. The RMP version 2.0 has also been submitted."}, {"id":"II/0017","type":"II","opinion":"2023-11-30","decision":"2024-02-01","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC in order to update drug-drug interaction information with dual inhibitors of CYP3A4 and CYP2C19, based on final results from study FEDR-CP-004; this is a phase 1, open-label study to evaluate the effect of a dual CYP2C19 and CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fedratinib in healthy adult subjects."}, {"id":"II/0010/G","type":"II","opinion":"2023-02-23","decision":"2024-02-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add new warnings on major adverse cardiac events (MACE), thrombosis and secondary malignancies. The updates pertain to three signals, which were identified with another JAK inhibitor (tofacitinib) indicated in rheumatoid arthritis; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"IAIN/0009","type":"IAIN","opinion":"2021-12-07","decision":"2022-12-19","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0005","type":"T","opinion":"2021-09-10","decision":"2021-10-19","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0003/G","type":"II","opinion":"2021-07-15","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.1"],"scope":"Update of sections 4.4 and 4.5 of the SmPC in order to update drug-drug interaction information regarding medicinal products renally excreted via organic cation transporter (OCT)2 and multidrug and toxin extrusion (MATE)1/2-K (e.g. metformin) based on data from study FEDR-CP-003 (drug transporter DDI Study) listed as recommendation during initial assessment. The Package Leaflet is updated accordingly. In addition, the MAH is updating the recently revised ATC code in section 5.1 of the SmPC."} ] }, "fruquintinib__fruzaqla": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/fruzaqla-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/fruzaqla-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000335647","type":"II","opinion":"2026-09-17","decision":null,"affects":["SmPC"],"codes":["Q.II.b.1.e","Q.II.b.1.b","Q.II.b.2.a","Q.II.b.4.b","Q.II.b.3.a","Q.II.b.5.a","Q.II.c.1.d","Q.III.1.b.2","Q.II.c.3.b","Q.II.e.1.a.1","Q.II.e.2.a","Q.II.e.7.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"And labelling have been updated accordingly."}, {"id":"EMA/VR/0000339669","type":"IB","opinion":"2026-05-12","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol)"}, {"id":"IA/0004/G","type":"IA","opinion":"2024-11-26","decision":null,"affects":["Annex II","PL"],"codes":["A.7","A.4","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2024-07-18","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Secondary packaging site"} ] }, "fulvestrant__faslodex": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/faslodex-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/faslodex-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000248153","type":"IB","opinion":"2025-05-14","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"To update section 4.4 of the SmPC and section 2 of the Package Leaflet to reflect the beer and wine content. Furthermore, the Marketing Authorisation Holder has taken the opportunity to delete the United Kingdom (Northern Ireland) from the list of local representatives."}, {"id":"N/0074","type":"N","opinion":"2022-08-29","decision":"2025-03-12","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0077/G","type":"IAIN","opinion":"2024-03-20","decision":"2025-03-12","affects":["Annex II","PL"],"codes":["A.7","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0068","type":"II","opinion":"2020-04-02","decision":"2020-10-27","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the safety and efficacy information based on the results from study Phase 3 Study A5481023 (PALOMA-3) a randomized controlled study of fulvestrant and palbociclib combination. In addition, the MAH took the opportunity to make a number of editorial changes to the PI to comply with the new QRD template v10.1 and the addition of the respective strength and pharmaceutical form to the corresponding Marketing Authorisation Number."}, {"id":"II/0067","type":"II","opinion":"2019-11-07","decision":"2020-10-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"To update the information on women of childbearing potential in section 4.6 of the SmPC following an review of non-clinical data, clinical pharmacology simulation/modelling data, supporting documentation and safety data; the Package Leaflet is updated accordingly. In addition, the MAH has taken the opportunity to correct a minor mistake in the address of one of the manufacturers responsible for batch release in Annex II and PL."}, {"id":"IB/0064","type":"IB","opinion":"2018-09-06","decision":"2019-08-01","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0066/G","type":"IAIN","opinion":"2019-04-02","decision":"2019-08-01","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0063","type":"T","opinion":"2018-02-27","decision":"2018-03-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0059","type":"II","opinion":"2017-10-12","decision":"2017-11-10","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication to include the use of Faslodex in combination with palbociclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy; in pre- or perimenopausal women, the combination treatment with palbociclib should be combined with a luteinizing hormone releasing hormone (LHRH) agonist for Faslodex. As a consequence, sections 2, 4.1, 4.2, 4.4, 4.8, 5.1, 5.3, 6.1, 6.5 and 6.6 of the SmPC are updated to update the safety and efficacy information. The Package Leaflet is updated in accordance."}, {"id":"IAIN/0062","type":"IAIN","opinion":"2017-09-25","decision":"2017-11-10","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0057","type":"II","opinion":"2017-06-22","decision":"2017-07-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","4.9","5.1"],"scope":"Extension of indication to include the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women who have not been previously treated with endocrine therapy. As a consequence, sections 4.1, 4.8, 4.9, and 5.1 of the SmPC are updated in order to update the safety and efficacy information. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce minor changes in the SmPC."}, {"id":"II/0055","type":"II","opinion":"2016-07-21","decision":"2017-05-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","6.6"],"scope":"Update of sections 4.2, 4.4, 4.8 and 6.6 of the SmPC in order to add precautionary language regarding the method of administration due to the proximity of the underlying sciatic nerve. In addition, the MAH update section 4.5 of the SmPC to include a warning of possible falsely elevated levels of estradiol in the use antibody based-estradiol assays in patients taking fulvestrant. The Package Leaflet and Labelling are updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the SmPC in accordance with the latest QRD template and update the list of local representatives in the Package Leaflet."}, {"id":"IAIN/0056","type":"IAIN","opinion":"2016-06-24","decision":"2017-05-22","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0047","type":"II","opinion":"2015-03-26","decision":"2016-03-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.2"],"scope":"Update of section 4.8 of the SmPC in order to add ‘reduced platelet count’ as an uncommon ADR. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make editorial changes to sections 4.8 and 5.2 of the SmPC."}, {"id":"IAIN/0051","type":"IAIN","opinion":"2015-09-11","decision":"2016-03-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0040","type":"N","opinion":"2013-09-13","decision":"2013-12-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0036","type":"II","opinion":"2013-01-17","decision":"2013-12-18","affects":["SmPC","Annex II"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"The MAH proposed the update of section 5.1 of the SmPC to include the final overall survival data from Study D6997C00002 (CONFIRM) further to the assessment of FUM021. Furthermore, the MAH proposed this opportunity to bring the PI in line with the latest QRD template version 8.2 and to implement minor editorial changes."}, {"id":"IB/0037","type":"IB","opinion":"2012-12-14","decision":"2013-12-18","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0034","type":"II","opinion":"2012-01-19","decision":"2012-02-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add new hepatobiliary disorders following a safety database research performed by the MAH. Section 4 of the package leaflet was proposed to be updated accordingly. Furthermore, the MAH took this opportunity to update the list of local representatives in the PL and to bring the PI in line with the latest QRD template (version 8.1, October 2011)."}, {"id":"II/0033","type":"II","opinion":"2012-01-19","decision":"2012-02-17","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC to include safety information further to the assessment of the two-year mouse carcinogenicity study 0118CM (FUM 002)."}, {"id":"II/0025","type":"II","opinion":"2011-06-23","decision":"2011-07-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.1","5.2"],"scope":"Update of sections 4.2, 4.4, 5.1 and 5.2 the SmPC based on paediatric data from Study D6992C0044 further to the assessment of the paediatric Article 46 follow up measure (P46 022). In addition Annex II has been updated to reflect the latest Risk Management Plan version number. Furthermore the MAH took the opportunity to update the local representative contact details in the package leaflet."}, {"id":"IG/0035","type":"IG","opinion":"2011-01-07","decision":null,"affects":["Annex II"],"codes":["C.I.9.i"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change(s) to a DDPS following the assessment of the same DDPS in relation to another medicinal product of the same MAH"}, {"id":"II/0018","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.8","5.1","5.3"],"scope":"Section 5.1 of the SmPC has been updated to include information on patients who have failed on prior anti-estrogen and aromatase inhibitor therapy. Moreover results relating to the mechanism of action, effects on bone and postmenopausal endometrium have also been included. In addition, section 4.8 of the SmPC has been updated to include bleeding at the injection site and information on arteritis in dogs has been included in section 5.3 of the SmPC. The Package Leaflet has been updated accordingly."}, {"id":"IB/0022","type":"IB","opinion":"2010-04-09","decision":"2010-04-09","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"II/0017","type":"II","opinion":"2010-01-21","decision":"2010-03-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.6","4.7","4.8","5.1","5.2","6.5","6.6"],"scope":"Change in the dose regimen from 250mg to 500mg, based on data from the CONFIRM study (previously assessed in FUM 005). As a consequence, sections 4.2, 4.7, 4.8, 5.1 and 5.2 of the SPC have been updated. Further, sections 6.5 and 6.6 have been updated for increased clarity. Section 4.6 has also been revised to include recommendations during lactation. The Package Leaflet has been updated accordingly. In addition, the MAH takes the opportunity to make minor editorial changes to the SPC, Labelling and Package Leaflet, including an update of the contact details of the Slovenian local representative in the Package Leaflet."}, {"id":"R/0014","type":"R","opinion":"2008-10-23","decision":"2008-12-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0013","type":"N","opinion":"2008-05-20","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0008","type":"II","opinion":"2006-09-21","decision":"2006-10-20","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of SPC"}, {"id":"N/0004","type":"N","opinion":"2005-10-24","decision":null,"affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0003","type":"II","opinion":"2005-05-26","decision":"2005-07-05","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of or change(s) to the pharmaceutical documentation"}, {"id":"II/0002","type":"II","opinion":"2005-05-26","decision":"2005-07-05","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5","4.8"],"scope":"The MAH applied to update the SPC in section 4.5 following the results of an in vitro study on P450 inhibion and to include \"elevated liver enzymes\" in section 4.8. The PL has been amended accordingly and in addition, changes to the adresses of local representatives have been implemented."}, {"id":"N/0001","type":"N","opinion":"2004-06-17","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "futibatinib__lytgobi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lytgobi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lytgobi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000282565","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.2"],"scope":"Update of sections 4.2, 4.4, 4.5 and 5.2 of the SmPC in order to revise the drug-drug interaction information based on the final results of study TAS-120-110. This is a Phase 1, open-label, fixed-sequence study to assess the effect of futibatinib on P-gp and BCRP and the effect of P-gp inhibition by quinidine on the pharmacokinetics of futibatinib in healthy adult subjects. The Package Leaflet is updated accordingly. geometric mean ratios for Cmax and AUCinf were 110% and 113%, respectively, when co-administered in healthy subjects with futibatinib relative to rosuvastatin alone."}, {"id":"IB/0001","type":"IB","opinion":"2023-10-10","decision":"2024-05-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"} ] }, "gefitinib__iressa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/iressa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IAIN/0039/G","type":"IAIN","opinion":"2023-07-14","decision":"2024-07-05","affects":["Annex II","PL"],"codes":["A.5.a","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"IA/0037","type":"IA","opinion":"2022-07-04","decision":"2023-09-15","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0034","type":"II","opinion":"2021-01-14","decision":"2022-02-04","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add Palmar-plantar erythrodysaesthesia syndrome to the list of adverse drug reactions (ADRs) with frequency uncommon; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1."}, {"id":"IAIN/0032/G","type":"IAIN","opinion":"2019-03-27","decision":"2020-03-09","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.2","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"IB/0029","type":"IB","opinion":"2018-04-23","decision":"2019-04-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0027","type":"II","opinion":"2017-01-26","decision":"2017-03-29","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update information on mechanisms of resistance to gefitinib in patients with EGFR mutation positive Non-Small Cell Lung Cancer (NSCLC) as proposed during assessment of LEG 21. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce some editorial changes in the SmPC"}, {"id":"II/0026","type":"II","opinion":"2017-02-23","decision":"2017-03-29","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.1"],"scope":"Update of section 4.1 of the SmPC in order to specify that Iressa should be used as monotherapy and not in combination with other medicines in its approved indication based on the submission of the final study report of the IMPRESS (D791LC00001) study following the PRAC recommendation in conclusion to the assessment of the 8th PSUR. The RMP was updated in consequence in order to add as identified risk the continuation of gefitinib as add-on to chemotherapy in patients with secondary resistance to gefitinib (agreed version 10.0)."}, {"id":"II/0025","type":"II","opinion":"2016-09-15","decision":"2017-03-29","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the safety information on allergic reaction amending the frequency from Uncommon to Common. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to align the Package leaflet with the SmPC adding dry mouth as a common side effects in section 4. The MAH took also the opportunity to introduce minor editorial changes, to update the list of local representatives for Poland in the Package Leaflet and to bring the PI in line with the latest QRD template version 10.0."}, {"id":"II/0024","type":"II","opinion":"2016-09-15","decision":"2017-03-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update information that the clinical experience has not shown a causal association between QT prolongation and gefitinib."}, {"id":"II/0016","type":"II","opinion":"2014-09-25","decision":"2015-10-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"R/0012","type":"R","opinion":"2014-02-20","decision":"2014-04-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0011","type":"II","opinion":"2013-06-27","decision":"2014-04-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect the results of study D791AC00014 (IFUM). In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"II/0005","type":"II","opinion":"2012-03-15","decision":"2012-04-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a warning on the development of keratitis and ulcerative keratitis. The Package Leaflet was updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the Product Information was brought in line with the latest QRD template version 8."}, {"id":"II/0004","type":"II","opinion":"2011-06-23","decision":"2011-08-01","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"In this variation the MAH has updated the section 5.1 of the SmPC based on updated overall survival (OS) data from the IPASS study further to the request of the CHMP following the assessment of FUM 002. In addition to this, the MAH updated the section 5.1 of the SmPC with the efficacy outcomes of the EGFR mutation-unknown subgroup of patients from this study. The MAH also took the opportunity to update the list of the local representatives in the Package Leaflet."}, {"id":"IG/0035","type":"IG","opinion":"2011-01-07","decision":null,"affects":["Annex II"],"codes":["C.I.9.i"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change(s) to a DDPS following the assessment of the same DDPS in relation to another medicinal product of the same MAH"}, {"id":"II/0003/G","type":"II","opinion":"2010-10-21","decision":"2010-11-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","4.9"],"scope":"Update of section 4.8 of the Summary of Product Characteristics (SmPC) to update the frequency of hepatitis and to add the adverse reactions gastrointestinal perforation, skin fissures, bullous conditions, cutaneous vasculitis, cystitis and haemorrhagic cystitis further to safety reviews conducted by the Marketing Authorisation Holder (MAH). Section 4.4 of the SmPC was also updated to reflect the information relative to hepatitis and gastrointestinal perforation. The Package Leaflet was amended accordingly. The MAH also updated section 4.9 \"overdose\" of the SmPC based on new available data from a high dose study."}, {"id":"II/0002","type":"II","opinion":"2009-12-17","decision":"2010-01-19","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of Pharmacovigilance System (DDPS). Consequently, Annex II has been revised with the new version number of the agreed DDPS (version 10). Minor updates were implemented in the Risk Management Plan."}, {"id":"IA/0001","type":"IA","opinion":"2009-09-17","decision":"2009-09-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units within range of appr. pack size"} ] }, "gemtuzumab-ozogamicin__mylotarg": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/mylotarg-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/mylotarg-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"II/0030","type":"II","opinion":"2023-10-12","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1, and 5.2 of the SmPC in order to update efficacy, pharmacokinetic and safety information based on interim results from study WI203680 - MyeChild 01-International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia – Incorporating an Embedded Dose Finding Study for Gemtuzumab Ozogamicin in Combination With Induction Chemotherapy. This is a dose finding sub-study aimed to identify the optimum tolerated number of doses of GO 3 mg/m2 (up to a maximum of 3 doses) which can be combined safely with AraC plus mitoxantrone or liposomal DAUNO in induction therapy."}, {"id":"R/0025","type":"R","opinion":"2022-09-15","decision":"2022-11-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0022","type":"N","opinion":"2021-10-01","decision":"2022-11-15","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0024","type":"II","opinion":"2022-06-23","decision":"2022-11-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1, and 5.2 of the SmPC based on the final results from study B176103; this is a single-arm, open-label, phase 4 study evaluating the QT interval, pharmacokinetics, and safety of gemtuzumab ozogamicin as a single-agent regimen in patients with relapsed or refractory CD33-positive Acute Myeloid Leukemia. The RMP version 2.2 has also been submitted. In addition, the MAH took the opportunity to introduce some editorial changes in the product information."}, {"id":"II/0023/G","type":"II","opinion":"2022-03-10","decision":"2022-11-15","affects":["Annex II","PL"],"codes":["B.I.e.3","B.I.e.2","B.I.a.1.j","A.7","B.I.e.4.a","B.I.a.1.e","B.I.b.1.b","B.I.c.1.b","B.I.b.1.g","A.5.a","B.I.a.2.c","B.II.h.1.b.2","B.I.a.1.k","B.I.b.2.e","B.I.a.3.c","B.I.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Which may have a significant impact on the medicinal product and is not related to a protocol Update to the Adventitious Agents Safety Evaluation information - Replacement of obsolete studies related to manufacturing steps and adventitious agents already reported in the dossier - without modifications of risk assessment Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - New storage site of MCB and/or WCB Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product Change in test procedure for AS or…"}, {"id":"IA/0026","type":"IA","opinion":"2022-07-11","decision":"2022-11-15","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0020","type":"N","opinion":"2020-11-27","decision":"2021-04-30","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0019/G","type":"IB","opinion":"2020-11-11","decision":"2021-04-30","affects":["SmPC","Annex II","PL"],"codes":["A.7","B.II.f.1.b.3","B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IB/0018","type":"IB","opinion":"2020-11-10","decision":"2021-04-30","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0014/G","type":"IAIN","opinion":"2020-05-18","decision":"2021-04-30","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0008","type":"II","opinion":"2019-09-19","decision":"2019-10-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in relation to posology and administration and with information regarding traceability, respectively. Following the re-analysis of data from the paediatric study AAML0531 sections 4.8 and 5.1 of the SmPC are also updated with information on safety and efficacy of Mylotarg in previously untreated AML patients. In addition, the Marketing authorisation holder (MAH) took the opportunity to include minor editorial changes in sections 4.2, 4.4, 4.8 and 5.2 of the SmPC and to make minor updates to bring the PI in line with the latest QRD template version."}, {"id":"II/0007","type":"II","opinion":"2019-09-19","decision":"2019-10-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC based on safety and efficacy data for paediatric patients with relapsed or refractory AML from a systematic literature review, as requested by the gemtuzumab ozogamicin Paediatric Investigation Plan (PIP) EMEA-001733-PIP02-15-M01 (measure 4)."}, {"id":"IB/0004/G","type":"IB","opinion":"2018-12-10","decision":"2019-10-21","affects":["Annex II","PL"],"codes":["A.4","A.5.b","B.II.d.2.a","B.I.b.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change in test procedure for the finished product - Minor changes to an approved test procedure; Change in the specification parameters and/or limits of an AS, starting material/intermediate/reagent - Other variation"}, {"id":"T/0001","type":"T","opinion":"2018-07-11","decision":"2018-07-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "gilteritinib__xospata": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/xospata-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"R/0017","type":"R","opinion":"2024-04-25","decision":"2024-06-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0013","type":"II","opinion":"2023-10-12","decision":"2024-06-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 in order to update the information on renal impairment based on final results from study 2215-CL-0114, listed as a category 3 study in the RMP. Study 2215-CL-0114 is a phase 1, single-dose, open-label study to investigate the effect of renal impairment on gilteritinib pharmacokinetics, safety and tolerability in 9 participants with severe renal impairment compared to 8 participants with normal renal function. The RMP version 5.0 has also been agreed during the procedure and submitted. In addition, the MAH took the opportunity to introduce editorial changes."}, {"id":"IAIN/0018","type":"IAIN","opinion":"2024-04-12","decision":"2024-06-27","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0003","type":"II","opinion":"2020-12-03","decision":"2021-12-09","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of section 4.4, 4.5 and 5.2 of the SmPC in order to update information about Transporter drug-drug interactions based on final results from in vitro transporter studies identified as recommendations by CHMP (REC003) during the initial approval. In addition, the MAH took the opportunity to perform minor corrections and editorial changes in the PI."}, {"id":"IA/0006","type":"IA","opinion":"2021-08-13","decision":"2021-12-09","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "glasdegib__daurismo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/daurismo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"R/0015","type":"R","opinion":"2025-01-30","decision":"2025-03-31","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0014","type":"IAIN","opinion":"2024-08-26","decision":"2025-03-31","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"IB/0007","type":"IB","opinion":"2022-07-05","decision":"2023-06-29","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"N/0001","type":"N","opinion":"2020-11-27","decision":"2022-03-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0004/G","type":"IB","opinion":"2021-06-10","decision":"2022-03-28","affects":["SmPC"],"codes":["B.II.b.4.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change from a single batch size to a batch size range of the finished product from 23.1 kg to 18.5 kg. To change the ATC Code of glasdegib from L01XX63 to L01XJ03. The MAH has taken this opportunity to update the Product Information Annexes III A & III B with minor administrative updates."}, {"id":"IB/0003/G","type":"IB","opinion":"2021-04-15","decision":"2022-03-28","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change to an approved stability protocol"} ] }, "glofitamab__columvi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/columvi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/columvi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000327100","type":"II","opinion":"2026-09-03","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add a new warning on ‘haemophagocytic lymphohistiocytosis’ and to add it to the list of adverse drug reactions (ADRs) with frequency not known, based on a drug safety report. The Package Leaflet is updated accordingly. The RMP version 6.0 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial and administrative changes to the PI."}, {"id":"EMA/VR/0000270570","type":"II","opinion":"2025-07-24","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","6.6"],"scope":"A grouped application consisting of three Type II variations, as follows: Update of sections 4.2 and 4.4 of the SmPC in order to add information regarding opportunistic infections based on a review of data from clinical trials, post-marketing surveillance, and literature. The Package Leaflet is updated accordingly. Update of sections 4.8 of the SmPC in order to add colitis as an adverse reaction with frequency uncommon based on a review of data from clinical trials, post-marketing surveillance, and literature. The Package Leaflet is updated accordingly."}, {"id":"II/0010","type":"II","opinion":"2025-02-27","decision":"2025-05-08","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Submission of the updated 2-year follow-up report from study NP30179 listed as a Specific Obligation in the Annex II of the Product Information. This is a multicenter, open-label Phase I/II study to evaluate the safety, efficacy, tolerability, and pharmacokinetics of escalating doses of glofitamab in patients with relapsed/refractory B-cell Non-Hodgkin’s Lymphoma (NHL). The Annex II is updated accordingly. Consequently, the MAH proposes a switch from conditional marketing authorisation to full marketing authorisation. An editorial update in section 5.1 of the SmPC is made as the statement on CMA is removed. The PL is updated accordingly. The RMP version 5.0 was submitted."}, {"id":"II/0005","type":"II","opinion":"2025-02-27","decision":"2025-04-10","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with gemcitabine and oxaliplatin the treatment of adult patients with relapse or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) who are ineligible for autologous stem cell transplant (ASCT) for COLUMVI, based on results of primary and updated analyses from study GO41944 (STARGLO) listed as a Specific Obligation in the Annex II of the Product Information, as well supportive data from the Phase Ib study GO41943."}, {"id":"IB/0008","type":"IB","opinion":"2024-12-11","decision":"2025-04-10","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"EMA/VR/0000249350","type":"IB","opinion":"2025-03-26","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.IV.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change of a measuring or administration device - Other variation"}, {"id":"IB/0001","type":"IB","opinion":"2024-01-03","decision":"2024-05-27","affects":["SmPC","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "ibrutinib__imbruvica": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/imbruvica-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/imbruvica-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"II/0092","type":"II","opinion":"2025-06-19","decision":"2025-07-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include Imbruvica in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) alternating with R-DHAP without IMBRUVICA, followed by Imbruvica monotherapy, is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who would be eligible for autologous stem cell transplantation (ASCT)."}, {"id":"II/0088/G","type":"II","opinion":"2025-02-20","decision":"2025-07-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"A grouped application consisting of: C.I.4: Update of section 5.1 of the SmPC based on results from Study CLL3011 (GLOW study). This is a Randomized, Open-label, Phase 3 Study of the Combination of Ibrutinib plus Venetoclax versus Chlorambucil plus Obinutuzumab for the First-line Treatment of Subjects with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). C.I.4: Update of section 5.1 of the SmPC based on results from Study PCYC-1116-CA. This is an Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)."}, {"id":"PSUSA/00010301/202311","type":"PSUSA","opinion":"2024-06-27","decision":"2024-08-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0083","type":"II","opinion":"2024-01-25","decision":"2024-08-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.1"],"scope":"Update of section 5.1 of the SmPC following the 24-month extended follow up from primary analysis data from Study CLL3011. This is a randomized, open-label, Phase 3 Study of the combination of Ibrutinib plus Venetoclax versus Chlorambucil plus Obinutuzumab for the First-line Treatment of Subjects with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). In addition, the MAH took the opportunity to add a footnote to the dose modifications table for non-cardiac events in section 4.2 to define the grading systems used for the adverse reactions."}, {"id":"PSUSA/00010301/202211","type":"PSUSA","opinion":"2023-06-22","decision":"2023-09-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"IAIN/0080/G","type":"IAIN","opinion":"2023-04-03","decision":"2023-09-15","affects":["Annex II","PL"],"codes":["B.II.b.2.c.2","B.II.b.1.a","B.II.b.1.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site"}, {"id":"II/0075","type":"II","opinion":"2022-10-13","decision":"2022-11-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC to incorporate information specific for dose modifications for non-cardiac events and events of cardiac failure or cardiac arrhythmias events based on data pool from clinical studies which included 4 Phase II (PCYC-1102-CA, PCYC-1104-CA, PCYC-1118E, PCYC-1142-CA) and 8 Phase III studies (PCYC-1112-CA, PCYC-1115-CA, CLL3001, PCYC-1130-CA, MCL3001, PCYC-1127-CA, CLL3011, and MCL3002)."}, {"id":"II/0074","type":"II","opinion":"2022-07-21","decision":"2022-08-24","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of section 4.2, 4.8, 5.1, and 5.2 of the SmPC in order to update the information related to Paediatrics following assessment done in procedure P46/035, based on results from the paediatric study LYM3003 “A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma”. The Package Leaflet is updated accordingly."}, {"id":"II/0069","type":"II","opinion":"2022-07-21","decision":"2022-08-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of the SmPC section 4.4. to include information on fatal and serious cardiac arrythmias and cardiac failure, relevant warnings and periodical monitoring of patients and update of the SmPC Section 4.8 to include cardiac arrest as an ADR following a safety assessment for increased risk of sudden death/cardiac death with the use of ibrutinib. Section 2 of the PL has been updated accordingly. Typographical errors have been corrected throughout the PI. The revised RMP version 19.4 has been submitted."}, {"id":"IB/0076/G","type":"IB","opinion":"2022-07-12","decision":"2022-08-24","affects":["SmPC","Labelling"],"codes":["B.II.e.6.b","B.II.e.5.z","B.II.b.1.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that does not affect the product information; Change in pack size of the finished product - Other variation; Replacement or addition of a manufacturing site for the FP - Primary packaging site"}, {"id":"II/0070","type":"II","opinion":"2022-06-23","decision":"2022-08-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of the existing CLL indication to include combination treatment with venetoclax for previously untreated patients based on efficacy and safety data from phase 3 study GLOW and phase 2 study CAPTIVATE; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC are updated. The package leaflet is updated accordingly. The RMP was amended as version 19.3 in line with the extension of indication."}, {"id":"II/0068","type":"II","opinion":"2021-12-02","decision":"2022-08-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add baseline monitoring in addition to the current warnings for periodic monitoring of cardiac failure and cardiac arrhythmias in patients receiving ibrutinib. The Package Leaflet is updated accordingly. The RMP version 18.2 has also been submitted."}, {"id":"PSUSA/00010301/202011","type":"PSUSA","opinion":"2021-06-24","decision":"2021-08-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"N/0067","type":"N","opinion":"2021-06-17","decision":"2021-08-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0064","type":"II","opinion":"2021-01-28","decision":"2021-08-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of the SmPC section 5.1 to include PFS2 and data from the final analysis with long term follow-up relevant to the Waldenström’s macroglobulinaemia (WM) indication and section 4.8, to include the long-term safety cumulative data - following the submission of the addendum to the final clinical study report from Study PCYC-1127-CA. In addition, an amendment to section 4.4 of the SmPC to add adequate language regarding excipients with known effect and an amendment to Table 1 of the SmPC to include a footnote by cardiac failure to reflect inclusion of events with fatal outcomes were implemented."}, {"id":"IAIN/0065/G","type":"IAIN","opinion":"2021-01-07","decision":"2021-08-20","affects":["SmPC","PL"],"codes":["A.6","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0059","type":"II","opinion":"2020-07-23","decision":"2020-08-28","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication in chronic lymphocytic leukaemia (CLL) to add combination with rituximab as follows: In combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL. This extension of the approved CLL indication is based on results from the Phase 3 Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG ACRIN) Study E1912 (also referred to as PCYC-1126e-CA). The SmPC is revised to include information related to the new indication. The PL has been revised accordingly. Minor editorial changes have been implemented in Annex IIIA. An updated RMP has been submitted."}, {"id":"PSUSA/00010301/201911","type":"PSUSA","opinion":"2020-06-25","decision":"2020-08-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0058","type":"II","opinion":"2020-04-17","decision":"2020-07-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.6","5.2"],"scope":"Update of Sections 4.5, 4.6 and 5.2 of the SmPC following the results from study CLL1017 (MEA 012.2). The PL is updated accordingly. In addition, the MAH took the opportunity to update the PI to the latest QRD template v10.1."}, {"id":"II/0053","type":"II","opinion":"2019-12-05","decision":"2020-07-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with final results on PFS by investigator assessment in Study PCYC-1112-CA, including PFS2 and overall survival data until study closure per protocol at 65-months follow-up. The Annex II is updated accordingly with deletion of ANX 003. The contact details of the local representatives have been updated in the Package Leaflet. Minor editorial revisions have been proposed throughout the PI."}, {"id":"II/0052","type":"II","opinion":"2019-12-05","decision":"2020-07-17","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC based on final results from study PAM 3038-1, which assessed long term safety data collected from predefined cohorts of subjects treated with ibrutinib for up to 5 years or until disease progression or unacceptable toxicity at the recommended daily doses of 420 mg/day for CLL/SLL and 560 mg/day for MCL (MEA 025)."}, {"id":"II/0048","type":"II","opinion":"2019-07-25","decision":"2020-07-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to amend the existing warning on bleeding-related events based on the final report of the non-interventional PASS PCYC-PMR-2060-4 aimed to evaluate the risks of major haemorrhage with the administration of Imbruvica; this is a category 3 study in the RMP."}, {"id":"IAIN/0057","type":"IAIN","opinion":"2019-11-22","decision":"2020-07-17","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010301/201811","type":"PSUSA","opinion":"2019-06-27","decision":"2019-09-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"N/0051","type":"N","opinion":"2019-05-08","decision":"2019-08-02","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0047","type":"II","opinion":"2019-06-27","decision":"2019-08-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include combination use with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) for Imbruvica based on data from the phase 3 study PCYC-1130-CA; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the SmPC and Package Leaflet with minor editorial/administrative changes. An updated RMP (version 12) is agreed."}, {"id":"II/0046","type":"II","opinion":"2019-06-27","decision":"2019-08-02","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8"],"scope":"Extension of Indication to include treatment of adult patients with Waldenström's macroglobulinaemia (WM) in combination with rituximab; as a consequence, section 4.1 and 4.8 of the SmPC are updated. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the SmPC and Package Leaflet with minor editorial/administrative changes. An updated RMP (version 12) was agreed."}, {"id":"R/0049","type":"R","opinion":"2019-04-26","decision":"2019-06-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0044","type":"N","opinion":"2018-10-12","decision":"2019-06-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0045/G","type":"IB","opinion":"2019-03-27","decision":"2019-06-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.1.a","B.II.b.1.e","B.II.b.2.a","B.II.b.2.c.1","B.II.b.3.a","B.II.b.4.a","B.II.b.5.a","B.II.b.5.z","B.II.e.2.z","B.II.e.5.a.1","B.II.e.5.a.2","B.II.e.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g."}, {"id":"PSUSA/00010301/201711","type":"PSUSA","opinion":"2018-06-28","decision":"2018-08-23","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0042","type":"II","opinion":"2018-05-31","decision":"2018-08-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update preclinical safety data information based on final results from a non-clinical carcinogenicity study in mouse (MEA011.1). In addition, the Marketing authorisation holder (MAH) took the opportunity to align the Package leaflet to information already included in the SmPC and to update the list of local representatives for Lithuania, Czech Republic, Netherlands, Slovenia and Portugal in the Package Leaflet."}, {"id":"X/0037","type":"X","opinion":"2018-04-26","decision":"2018-06-29","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"PSUSA/00010301/201705","type":"PSUSA","opinion":"2017-12-14","decision":"2018-02-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0033/G","type":"II","opinion":"2017-09-28","decision":"2018-02-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.11.a","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to update the safety information related to bleeding related events based on final results from study PCYC-1132-NT listed as a category 3 (MEA 004.1) study in the RMP; this is an in-vitro study to evaluate the effect of ibrutinib on platelet aggregation ;The Package Leaflet is updated accordingly. will be submitted in Q2 2017 and Q2 2018. Annex II has been updated accordingly. C.I.11.a (Type Iain) - To update the RMP to include an additional action for Study PCI-32765 CAN3001 (MEA017) to provide a ”further interim report in 5 years’ from time from the cut-off date of the current report (12 November 2015)”."}, {"id":"PSUSA/00010301/201611","type":"PSUSA","opinion":"2017-06-22","decision":"2017-08-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0029","type":"II","opinion":"2017-05-18","decision":"2017-08-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 of the SmPC to amend the statement on interaction between products increasing stomach pH and ibrutinib have not been studied and section 5.2 to include the findings from study CLL1005. The Package Leaflet is not impacted by these changes. In addition, the RMP is updated to version 6.3 to reflect this new safety information. The requested variation proposed amendments to the Summary of Product Characteristics and to the Risk Management Plan (RMP)."}, {"id":"II/0025","type":"II","opinion":"2017-02-23","decision":"2017-08-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of the SmPC section 4.4 to remove the warning and precaution regarding the effect of Ibrutinib on the QT interval and section 5.1 to provide additional information regarding the pharmacodynamic effect of Ibrutinib on QT/QTc intervals and cardiac electrophysiology. No changes to the Annex III Package Leaflet are proposed."}, {"id":"IB/0035","type":"IB","opinion":"2017-05-18","decision":"2017-08-24","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUSA/00010301/201605","type":"PSUSA","opinion":"2016-12-15","decision":"2017-02-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ibrutinib"}, {"id":"II/0027/G","type":"II","opinion":"2016-12-15","decision":"2017-02-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":[],"scope":"4.4 Special warnings and precautions for use Atrial fibrillation/flutter Atrial fibrillation and atrial flutter have been reported in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor all patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms or new onset of dyspnoea should be evaluated clinically and if indicated have an electrocardiogram (ECG) performed. 4.8 Undesirable effects they originated from spontaneous post-marketing reports."}, {"id":"II/0024","type":"II","opinion":"2016-07-21","decision":"2016-08-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order add a warning relating to Interstitial Lung Disease and to include it as a post-marketing adverse drug reaction with “common” frequency. The Package leaflet and RMP (version 6.1) are updated accordingly. In addition, the Marketing Authorisation Holder (MAH) took the opportunity to updated the list of local representatives in the Package Leaflet Furthermore, the PI is brought in line with the latest QRD template version 10."}, {"id":"II/0017/G","type":"II","opinion":"2016-07-21","decision":"2016-08-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of Indication for use of Imbruvica in combination with bendamustine and rituximab in patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC and the Annex II are updated. The Package Leaflet is updated in accordance. In addition, a clarification is made that the indications in mantle cell lymphoma (MCL) and Waldenstroem’s macroglobulinaemia (WM) refer to use of ibrutinib as single agent. In addition, the Marketing authorisation holder (MAH) introduced minor editorial changes throughout the product information. The RMP is updated accordingly (RMP version 6.1)."}, {"id":"II/0016","type":"II","opinion":"2016-04-28","decision":"2016-05-26","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.6","4.8","5.1","5.3"],"scope":"Extension of indication to add the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) based on the results from the final CSR of study PCYC-1115-CA (MEA 021). As a consequence, sections 4.1, 4.4, 4.6, 4.8, 5.1 and 5.3 of the SmPC have been updated. The Package Leaflet has been updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor editorial changes to the SmPC. A revised version of the RMP (version 5.0.3) has been approved as part of this application."}, {"id":"II/0013","type":"II","opinion":"2016-02-25","decision":"2016-05-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","4.9"],"scope":"Update of SmPC sections 4.8 and 4.9 with information on hepatic failure and hepatotoxicity. The PL and RMP are updated accordingly. Furthermore, the MAH took the opportunity to introduce editorial changes throughout the PI. The RMP version 4.5 was finally agreed."}, {"id":"II/0008/G","type":"II","opinion":"2015-07-23","decision":"2016-05-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0007/G","type":"II","opinion":"2015-10-22","decision":"2016-05-26","affects":["SmPC","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"As agreed in the RMP and in order to address the post-authorisation measures: • Submission of final non-clinical study report FK10654. • Submission of final non-clinical study report FK10655. • Submission of final non-clinical study report FK10656. • Submission of final non clinical study report FK10806. • Following the submission of the non-clinical study report FK10657, update of section 4.5 of the SmPC regarding BRCP inhibition. • Following the submission of the non-clinical study reports FK10597, FK10598, FK10606, FK10650, FK10775 and FK10805, update of section 4.5 of the SmPC to delete the CYP3A4 inhibition statement. • Following the submission of the non-clinical study reports…"}, {"id":"II/0004","type":"II","opinion":"2015-02-26","decision":"2015-07-03","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to include a new warning regarding ‘tumour lysis syndrome’ (TLS). The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC and Package Leaflet."}, {"id":"II/0003","type":"II","opinion":"2015-02-26","decision":"2015-07-03","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC with information related to patients with hepatic impairment, based on data from the final CSR for study PCI -32765CLL1006. The provision of study PCI-32765CLL1006 addresses MEA 014. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC, labelling and Package Leaflet."}, {"id":"II/0001","type":"II","opinion":"2015-05-21","decision":"2015-07-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of Indication to add treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC and the Package Leaflet have been updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC. Furthermore, an updated RMP version 4.1 was approved as part of the application."} ] }, "idecabtagene-vicleucel__abecma": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/abecma-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/abecma-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000293201","type":"II","opinion":"2025-11-13","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.7"],"scope":"Update of sections 4.2, 4.4, and 4.7 of the SmPC in order to change the post-approval safety monitoring requirements and driving restrictions after administration of Abecma; Annex II and the Package Leaflet are updated accordingly. The RMP version 5.1 has also been submitted."}, {"id":"EMA/VR/0000296162","type":"IAIN","opinion":"2025-09-16","decision":null,"affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"To update section 4.4 of the SmPC to implement the signal recommendations on 'Ciltacabtagene autoleucel; idecabtagene vicleucel; tisagenlecleucel – Progressive multifocal leukoencephalopathy (EPITT no 20153)' adopted at the 10 July 2025 PRAC."}, {"id":"II/0047","type":"II","opinion":"2024-09-19","decision":"2025-08-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["6.6"],"scope":"To update section 6.6 of the SmPC - “Special precautions for disposal and other handling”, and corresponding section of the Package Leaflet, to clarify dose preparation and administration instructions of the thawed finished product (IV administration set fitted with a non-leukodepleting in-line filter which can be used to reduce visible cellular aggregates that do not disperse after gentle manual mixing). In addition, the labelling has been updated to include information to appear on the infusion bag – chain of identity label and the package leaflet has been updated to include the local representatives of the MAH."}, {"id":"IAIN/0057","type":"IAIN","opinion":"2024-11-22","decision":"2025-08-22","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0055","type":"IAIN","opinion":"2024-09-03","decision":"2025-08-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"EMA/VR/0000273138","type":"IB","opinion":"2025-08-06","decision":null,"affects":["SmPC","PL"],"codes":["B.II.e.6.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation (such as colour of flip-off caps, colour code rings on ampoules, change of needle shield (different plastic used)) - Other changes"}, {"id":"PSUSA/00010954/202309","type":"PSUSA","opinion":"2024-04-25","decision":"2024-06-20","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - idecabtagene vicleucel"}, {"id":"II/0031","type":"II","opinion":"2024-01-25","decision":"2024-03-19","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","6.1","6.3","6.4","6.6"],"scope":"Extension of indication to include treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD-38 antibody and have demonstrated disease progression on the last therapy for Abecma (idecabtagene vicleucel, ide-cel), based on results from study BB2121-MM-003 (MM-003, KarMMa-3). This is a Phase 3, multicentre, randomised, open-label study to compare the efficacy and safety of ide-cel versus standard regimens in subjects with RRMM. As a consequence, sections 2.1, 2.2, 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 6.1, 6.3, 6.4 and 6.6 of the SmPC are updated."}, {"id":"IA/0040","type":"IA","opinion":"2023-09-07","decision":"2024-02-06","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00010954/202209","type":"PSUSA","opinion":"2023-04-26","decision":"2023-06-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - idecabtagene vicleucel"}, {"id":"R/0014","type":"R","opinion":"2022-04-22","decision":"2022-06-24","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0010","type":"II","opinion":"2022-01-27","decision":"2022-06-24","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on 24 month follow up data from the pivotal study submitted during initial MAA (BB2121-MM-001: A Phase 2, Multicenter Study to determine the Efficacy and Safety of bb2121 in Subjects with Relapsed and Refractory Multiple Myeloma) listed as a specific obligation in the Annex II and in the RMP; The annex II is updated with the proposed deletion of the relevant SOB. The RMP version 1.2 has also been submitted."}, {"id":"II/0009","type":"II","opinion":"2021-12-16","decision":"2022-01-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC, Annex IID and PIL in order to add statements for the use of Abecma exceptionally during shortage of tocilizumab following the \"CAT recommendation for the use of CAR-T cell-based therapies in EU during shortages of tocilizumab\""}, {"id":"T/0007","type":"T","opinion":"2021-11-04","decision":"2021-11-18","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0004/G","type":"IAIN","opinion":"2021-09-28","decision":"2021-11-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "idelalisib__zydelig": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zydelig-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"R/0059","type":"R","opinion":"2024-04-25","decision":"2024-06-20","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0057","type":"N","opinion":"2023-06-23","decision":"2024-06-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0051","type":"N","opinion":"2021-04-14","decision":"2021-09-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0049","type":"IB","opinion":"2020-10-15","decision":"2021-09-29","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0053","type":"IA","opinion":"2021-09-15","decision":"2021-09-29","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0047","type":"II","opinion":"2019-11-14","decision":"2020-02-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Overall Response Rates (ORRs) reported in the final results of study 101-09 are consistent with the numbers previously reported for both Follicular Lymphoma (FL) patients and the whole study population, with a point estimate approximately 1% higher. The Complete Responses (CRs) in the FL subset doubled, from 8.3 to 16.7%, and the median Duration of Response (DOR) was 12.5 months in all patients and 11.8 in FL patients. The Kaplan-Meier estimate of median Overall Survival (OS), including long-term follow-up, was 48.6 months in the overall population, while in FL patients it was 61.2 months. Moreover, the safety findings were consistent with the known safety profile of idelalisib."}, {"id":"II/0045","type":"II","opinion":"2019-03-21","decision":"2020-02-28","affects":["Annex II"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"II/0044","type":"II","opinion":"2019-03-21","decision":"2020-02-28","affects":["Annex II"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"R/0043","type":"R","opinion":"2019-02-28","decision":"2019-04-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"T/0040","type":"T","opinion":"2018-04-25","decision":"2018-06-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00010303/201707","type":"PSUSA","opinion":"2018-02-22","decision":"2018-04-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - idelalisib"}, {"id":"II/0038","type":"II","opinion":"2018-01-25","decision":"2018-03-05","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to reflect information from a recent cumulative safety review of cases of organising pneumonia. The safety review resulted from the Marketing authorisation holder (MAH) MAH ongoing pharmacovigilance and signal detection for Zydelig. The RMP version 2.6 has also been submitted to extend the deadlines for submission of final CSRs for three studies linked with Annex II conditions. The MAH took this opportunity to make a minor amendment in the Labelling and to update the local representatives in the package leaflet."}, {"id":"II/0035/G","type":"II","opinion":"2017-11-30","decision":"2018-03-05","affects":["SmPC","Labelling"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to revise the carcinogenicity information for idelalisib based on final results from two long term carcinogenicity studies (TX-312-2017, TX-312-2019). The RMP version 2.3 has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 10.0."}, {"id":"II/0032/G","type":"II","opinion":"2018-02-22","decision":null,"affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"PSUSA/00010303/201701","type":"PSUSA","opinion":"2017-09-14","decision":"2017-11-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - idelalisib"}, {"id":"II/0025","type":"II","opinion":"2016-11-10","decision":"2017-11-16","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to reflect the results of the final report for a study of mechanisms of resistance to idelalisib in patients with chronic lymphocytic leukemia (CLL). This submission fulfils the post-authorisation measure (PAM) 013 for Zydelig."}, {"id":"IB/0036","type":"IB","opinion":"2017-07-31","decision":"2017-11-16","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0031","type":"IB","opinion":"2017-01-31","decision":"2017-11-16","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0030","type":"IB","opinion":"2016-11-16","decision":"2017-11-16","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0011","type":"II","opinion":"2016-02-25","decision":"2016-09-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of Indication for Zydelig to include the combination of idelalisib with ofatumumab; as a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives for United Kingdom, Ireland, Slovenia and Slovakia in the Package Leaflet."}, {"id":"II/0018","type":"II","opinion":"2016-04-28","decision":"2016-09-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information regarding Stevens-Johnson syndrome and toxic epidermal necrolysis based on post marketing experience. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the contact details of local representatives in Czech Republic and Slovakia in the Package Leaflet. The updated RMP version 1.9 has been agreed."}, {"id":"II/0017","type":"II","opinion":"2016-02-25","decision":"2016-09-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to amend the clinical recommendations for the co-administration of idelalisib with anticoagulants. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to amend the contact details of the local representatives for Belgium and Luxemburg in the Package Leaflet."}, {"id":"II/0006","type":"II","opinion":"2015-03-26","decision":"2016-02-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.3"],"scope":"Update of sections 4.8 and 5.1 of the SmPC, after submission of Final CSR for study GS-US-312-0116, in order to, respectively, update the safety information regarding rash and update the SmPC with final efficacy data. The relevant Annex II obligation was amended to reflect the submission of the final study report for GS-US-312-0116. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct typographical errors concerning repeated dose toxicity studies in rats and dogs in section 5.3 of the SmPC."}, {"id":"IG/0521","type":"IG","opinion":"2015-02-26","decision":"2016-02-11","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"IB/0019/G","type":"IB","opinion":"2016-01-14","decision":"2016-02-11","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0010","type":"IB","opinion":"2015-07-06","decision":"2016-02-11","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "imatinib__glivec": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/glivec-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/glivec-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000355356","type":"II","opinion":"2026-09-17","decision":"2026-10-19","affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to update the starting dose for patients with dermatofibrosarcoma protuberans (DFSP) to 400 mg/day, based on a recent review of published evidence demonstrating similar efficacy and improved tolerability compared with 800 mg/day. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000290092","type":"II","opinion":"2025-10-16","decision":"2026-07-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to add drug-drug interaction information with methotrexate based on reports of delayed excretion of high dose methotrexate when concomitantly administered with imatinib and improvement of methotrexate clearance when imatinib treatment was withheld. In addition, the MAH took the opportunity to introduce minor editorial and administrative changes to the PI, including an update to the list of local representatives in the Package Leaflet."}, {"id":"EMA/VR/0000282643","type":"IB","opinion":"2025-08-01","decision":"2026-07-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.7.a","A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of: - a pharmaceutical form; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0138","type":"IAIN","opinion":"2024-12-10","decision":"2025-04-17","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0135/G","type":"IAIN","opinion":"2024-04-10","decision":"2025-04-17","affects":["Annex II","PL"],"codes":["A.4","B.II.b.2.c.1","B.II.b.1.b","B.II.b.1.a","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site."}, {"id":"II/0133","type":"II","opinion":"2023-08-31","decision":"2024-03-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study CSTI571I2201 - A European observational registry collecting efficacy and safety data in newly diagnosed pediatric Ph+ ALL patients treated with chemotherapy + imatinib ± HSCT, listed as an obligation in the Annex II of the Product Information. This study has been designed as an observational, multi-center registry to collect efficacy and safety data in Ph+ ALL pediatric patients (ages 1 to <18 years old) treated with chemotherapy + imatinib, with or without (± HSCT) primarily in European countries. The Annex II and the RMP (version 13.0) are updated accordingly."}, {"id":"IB/0132/G","type":"IB","opinion":"2023-03-27","decision":"2024-03-26","affects":["SmPC","PL"],"codes":["B.II.b.5.z","B.II.a.4.a","B.II.a.2.a","B.II.a.1.a","B.II.a.1.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to in-process tests or limits applied during the manufacture of the finished product - Other variation; Change in coating weight of oral dosage forms or change in weight of capsule shells - Solid oral pharmaceutical forms; Change in the shape or dimensions of the pharmaceutical form - Immediate release tablets, capsules, suppositories and pessaries; Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings."}, {"id":"II/0129","type":"II","opinion":"2022-02-17","decision":"2023-02-03","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add pemphigus with frequency rare and osteonecrosis with frequency uncommon to the list of adverse drug reactions based on an analysis of pre-clinical data, scientific literature, clinical trial datasets, Novartis pharmacovigilance database, EVDAS and other safety databases. The Package Leaflet is updated accordingly. The MAH is also taking the opportunity to align section 4 of the PL with the already approved ADR section of the SmPC as a number of ADRs is not reflected accurately."}, {"id":"PSUSA/00001725/202105","type":"PSUSA","opinion":"2022-01-27","decision":"2022-03-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - imatinib"}, {"id":"IB/0128","type":"IB","opinion":"2021-12-08","decision":"2022-03-22","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IA/0126/G","type":"IA","opinion":"2021-08-11","decision":"2022-03-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0123","type":"N","opinion":"2021-04-19","decision":"2021-05-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0117","type":"II","opinion":"2020-05-28","decision":"2021-05-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC to include that women of childbearing potential must be advised to use effective contraception and stop breast-feeding during treatment and for at least 15 days after stopping treatment with imatinib, based on a company review of the company Core Data Sheet. The PL has been updated accordingly."}, {"id":"IB/0122/G","type":"IB","opinion":"2021-02-01","decision":"2021-05-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.7.b","C.I.11.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of - a strength; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of wording agreed by the competent authority"}, {"id":"IB/0120/G","type":"IB","opinion":"2020-10-22","decision":"2021-05-21","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.1.e","B.II.b.2.c.2","B.II.b.3.a","B.II.b.3.z","B.II.e.2.z","B.II.e.3.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process."}, {"id":"IAIN/0116/G","type":"IAIN","opinion":"2019-08-14","decision":"2020-04-03","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0114/G","type":"IA","opinion":"2019-05-10","decision":"2020-04-03","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.e.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Qualitative and quantitative composition - Solid pharmaceutical forms"}, {"id":"PSUSA/00001725/201805","type":"PSUSA","opinion":"2019-01-31","decision":"2019-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - imatinib"}, {"id":"T/0110","type":"T","opinion":"2018-05-16","decision":"2018-06-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0109","type":"II","opinion":"2018-03-22","decision":"2018-06-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC to add a new warning regarding phototoxicity, and section 4.8 of the SmPC to add the new ADR ‘pseudoporphyria’ with a frequency of ‘not known’. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the contact details of the local representatives in the Package Leaflet."}, {"id":"II/0108","type":"II","opinion":"2017-09-14","decision":"2018-06-25","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of SmPC section 4.4 based on the final CSR for study STI571A2405; the International Study for Chronic Myeloid Leukaemia (CML) in childhood and adolescents (I-CML-Ped Study). The provision of the study report addresses the post-authorisation measure MEA 162.8."}, {"id":"II/0106","type":"II","opinion":"2016-11-10","decision":"2017-05-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to update the safety information on the existing ADR ‘musculoskeletal pain including myalgia’ so as to inform that musculoskeletal pain during treatment with imatinib or after discontinuation has been observed in post-marketing. The Package Leaflet has been updated accordingly. Further, the MAH has taken the opportunity to merge the SmPCs of the different strengths of the same pharmaceutical form i.e. 50 mg and 100 mg hard capsules, and 100 mg and 400 mg film coated tablets, respectively, and to align the annexes with version 10 of the QRD template."}, {"id":"II/0104","type":"II","opinion":"2016-09-15","decision":"2017-05-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC, upon request by the CHMP, to reflect the results of Study CSTI571L2401, an observational registry collecting long-term safety and efficacy data in patients with myeloid neoplasms with platelet derived growth factor receptor beta rearrangement (MPN with PDGFRB rearrangement) treated with imatinib mesylate, in fulfilment of the post-authorisation measure MEA 168.8."}, {"id":"II/0100","type":"II","opinion":"2016-09-15","decision":"2017-05-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the Final Clinical Study Report for Study CSTI571A2403: “A global Gleevec/Glivec and Tasigna Pregnancy Exposure Registry” (Category 3)."}, {"id":"IB/0105","type":"IB","opinion":"2016-08-31","decision":"2017-05-08","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0102","type":"IAIN","opinion":"2016-05-11","decision":"2017-05-08","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0096","type":"II","opinion":"2015-02-26","decision":"2016-01-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to include chronic renal failure as an adverse drug reaction and a warning related to renal insufficiency following PRAC recommendation. The Package leaflet is updated accordingly."}, {"id":"II/0095","type":"II","opinion":"2014-12-18","decision":"2016-01-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of SmPC section 4.4 to include information about ‘Gastric Antral Vascular Ectasia’ (GAVE) under the existing warning ‘Gatrointestinal haemorrhage’, and SmPC section 4.8 to add GAVE as a new ADR. Further, SmPC section 4.8 has been aligned with current guidelines regarding table layout and estimation of frequencies of adverse reactions. In addition, the MAH took the opportunity to introduce standard text in the SmPC and Package Leaflet regarding additional monitoring in line with the latest QRD templates, and to implement minor editorial changes in the SmPC."}, {"id":"II/0093/G","type":"II","opinion":"2014-12-03","decision":"2016-01-14","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"C.I.4 was withdrawn during the procedure"}, {"id":"II/0090","type":"II","opinion":"2013-10-24","decision":"2014-07-18","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include the term \"Drug rash with eosinophilia and systemic symptoms\" (DRESS) under the SOC Skin and subcutaneous disorders with a frequency of unknown further to the PRAC request following the assessment of a cumulative review of cases of DRESS. The Package Leaflet was proposed to be updated accordingly. Furthermore, the MAH took the opportunity of this variation to add and correct information in the PL to bring it in line with the SmPC. Editorial changes were also proposed to the SmPC."}, {"id":"II/0089","type":"II","opinion":"2013-07-25","decision":"2014-07-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.3"],"scope":"Update of section 5.3 of the SmPC in order to reflect the results of a juvenile development toxicology study. In addition, the MAH took the opportunity to reflect in the PL the adverse drug reaction of “bleeding in the eyes” which was already listed in section 4.8 of the SmPC and update the list of local representatives in the Package Leaflet. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"IAIN/0091","type":"IAIN","opinion":"2014-06-19","decision":"2014-07-18","affects":["SmPC","PL"],"codes":["B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"II/0085","type":"II","opinion":"2012-11-15","decision":"2013-06-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC in order to reflect paediatric data related to rare diseases. The Package Leaflet was proposed to be updated accordingly."}, {"id":"II/0084","type":"II","opinion":"2012-11-15","decision":"2013-06-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 undesirable effects of the SmPC in order to include the term subdural haematoma with the CIOMS frequency of \"uncommon\". The Package Leaflet is updated accordingly."}, {"id":"II/0080","type":"II","opinion":"2013-05-30","decision":"2013-06-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2","5.3"],"scope":"Extension of the indication for the treatment of paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ALL) integrated with chemotherapy. Consequently, the MAH proposed the update of sections 4.1, 4.2, 4.8, 5.1, 5.2 and 5.3 of the SmPC. The Package Leaflet was updated in accordance. Furthermore, the MAH proposed this opportunity to bring the PI in line with the latest QRD template version 9."}, {"id":"IAIN/0086","type":"IAIN","opinion":"2012-11-09","decision":"2013-06-27","affects":["SmPC","PL"],"codes":["B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"II/0082","type":"II","opinion":"2012-09-20","decision":"2012-10-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC to update the information on interaction with potent strong CYP3A4 inhibitors and CYP3A4 substrates with narrow therapeutic window as well as to provide guidance on the use of low molecular weight heparin as an alternative to warfarin. In addition, section 4.4 has been updated to clarify the information pertaining to hypereosinophilic syndrome (HES) and cardiac disease. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0070","type":"II","opinion":"2012-01-19","decision":"2012-02-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of section 4.2 Posology and method of administration of the SmPC to indicate that the length of treatment in the clinical trial supporting the adjuvant treatment of adult patients following resection of GIST was 36 months following results of the CSTI571BFI03 study (FUM 180). Section 5.1 Pharmacodynamic properties of the SmPC has also been updated to reflect the efficacy data of the study."}, {"id":"II/0073","type":"II","opinion":"2011-12-15","decision":"2012-01-20","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 special warnings and precautions to include patients with history of renal failure as a caution regarding the risk of oedema and fluid retention as requested by the CHMP following the assessment of the risk management plan version 4.0 (RM2 176.2)."}, {"id":"II/0072","type":"II","opinion":"2011-12-15","decision":"2012-01-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","4.7"],"scope":"Update of section 4.6 Fertility pregnancy and lactation of the SmPC to introduce a sub-section on fertility. Section 4.7 Effects on ability to drive and use machines of the SmPC was updated to include somnolence as one of the undesirable effects experienced by patients treated with Glivec. The PL has been amended accordingly. In addition, the MAH took the opportunity of this variation to bring the PI in line with the latest QRD template version 8.0 and included minor editorial comments"}, {"id":"II/0071","type":"II","opinion":"2011-11-17","decision":"2011-12-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.1"],"scope":"Following a revision of its Core Data Sheet (CDS), the MAH updated section 5.1 of the SmPC to include a mechanism of action sub-section. In addition existing information in section 4.5 of the SmPC related to interactions with medicinal products were reflected in section 4.4. Other editorial changes are included in sections 4.2, 4.4 and 4.5."}, {"id":"II/0064","type":"II","opinion":"2011-04-14","decision":"2011-05-23","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1"],"scope":"This type II variation concerns an update of section 4.5 of the Summary of Product Characteristics (SmPC) to revise information regarding drug-drug interaction with paracetamol. In addition, the MAH took the opportunity of this variation to correct the number of patients in the GIST study included in section 5.1 of the SmPC. Minor editorial amendments have also been made to the Annex II."}, {"id":"II/0063","type":"II","opinion":"2011-01-20","decision":"2011-02-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"This type II variation concerns an update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) to include information regarding growth retardation in children following the review of the Novartis global safety database, clinical trial data and published literature. The Package leaflet has been updated accordingly."}, {"id":"II/0062","type":"II","opinion":"2010-11-18","decision":"2010-12-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"This type II variation concerns an update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) to include information regarding the risk of tumour lysis syndrome as requested by the CHMP following the assessment of FUM 184. The Package leaflet has been updated accordingly. Annex II has been revised to delete the version number of the DDPS."}, {"id":"II/0059","type":"II","opinion":"2010-02-18","decision":"2010-03-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"This type II variation concerns an update of section 4.8 of the SmPC to include palmoplantar erythrodysesthesia syndrome as a post-marketing adverse reaction further to the CHMP request following the assessment of PSUR 10. The Package leaflet has been updated accordingly. In addition, the MAH proposed further improvements to the Package Leaflet and took into account results from a user consultation. Furthermore, the MAH updated the list of local representatives in the Package Leaflet. The MAH also took the opportunity to update the Product information in line with the latest QRD template (version 7.3)."}, {"id":"II/0058","type":"II","opinion":"2010-02-18","decision":"2010-03-26","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance system (DDPS) to version 8.0, including a change of the Qualified Person for Pharmacovigilance (QPPV). Consequently, Annex II has been updated with the new version number of the agreed DDPS."}, {"id":"II/0050","type":"II","opinion":"2009-03-19","decision":"2009-04-29","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SPC concerning an efficacy update based on the availability of a 84 month data analysis from the pivotal phase III study (CSTI571A0106) in newly diagnosed CML patients. This variation also fulfills the MAH follow-up measure (FUM 128) related to the submission of the annual update of this clinical study, including molecular results."}, {"id":"II/0049","type":"II","opinion":"2009-03-19","decision":"2009-04-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.6","4.8","4.9"],"scope":"Update to section 4.2 to the posology for HES/CEL and update of the information on distribution in human milk under section 4.6, addition of Rhabdomyolysis, myopathy, Acute Generalized Exanthematous Pustulosis, ovarian haemorrhage, hemorrhagic ovarian cyst under section 4.8 and update of the information on overdose under section 4.9 of the SPC. The Package Leaflet has been updated accordingly. Furthermore, the SPC and Package Leaflet have been updated according to the latest QRD template."}, {"id":"II/0048","type":"II","opinion":"2009-03-19","decision":"2009-04-29","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment."}, {"id":"II/0045","type":"II","opinion":"2007-10-18","decision":"2007-11-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"The MAH has applied to update section 4.4 of the SPC on the observed increase in hepatotoxocity when used in combination with chemotherapy and section 4.8 to add the Adverse Events \"toxic epidermal necrolysis\", \"lichenoid keratosis\" and \"lichen planus\". The ATC code under section 5.1 was updated and typographical errors in Table 1 of section 4.8 of the SPC have also been corrected. The Package Leaflet has also been updated accordingly and also to reflect a number of adverse events that were already mentioned in the SPC. Furthermore, the contact details for the Slovakian and Latvian local representatives have been updated in the Package Leaflet."}, {"id":"S/0043","type":"S","opinion":"2007-02-22","decision":"2007-04-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0042","type":"II","opinion":"2007-02-22","decision":"2007-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the adverse drug reaction table in section 4.8 of the SPC, and to provide further information on congestive heart failure in imatinib treated patients. Furthermore, the contact details for Bulgaria and Romania have been added in the list of local representatives in section 6 of the Package Leaflet."}, {"id":"II/0041","type":"II","opinion":"2007-02-22","decision":"2007-03-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"The MAH has applied to update section 4.5 of the SPC with pharmacokinetic data regarding the effects of the co-administration with a CYP2D6 substrate (metoprolol) and CYP3A4 inducers (enzyme-inducing antiepileptic drugs and St. John's wort)."}, {"id":"N/0044","type":"N","opinion":"2007-02-12","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0040","type":"II","opinion":"2006-10-18","decision":"2006-11-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SPC with the results of a phase I clinical pharmacology study in patients with varying degrees of renal dysfunction, following the assessment of specific obligation data."}, {"id":"II/0039","type":"II","opinion":"2006-10-18","decision":"2006-11-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SPC (Special warnings and precautions for use) to include: hypothyroidism in patients receiving levothyroxine following thyroidectomy, as well as section 4.8 (Undesirable effects) to include: hepatic necrosis, anaphylactic reactions and acute respiratory failure following the assessments of the 5th, 6th and 7th PSURs. The Package Leaflet has also been updated accordingly."}, {"id":"II/0038","type":"II","opinion":"2006-10-18","decision":"2006-11-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.1","5.1"],"scope":"Update of Section 5.1 of the SPC with the 60 month data analysis from phase II study (CSTI571A0106) in newly diagnosed adult CML patients, which was part of the follow-up measures related to the approval of the indication. In addition, an existing statement in Section 4.1 of the SPC was amended to clarify that this is the only indication for Glivec where controlled trials have been perfomed, and to include the standard statements in the SPC and PL regarding Exceptional Circumstances."}, {"id":"II/0035","type":"II","opinion":"2006-10-18","decision":"2006-11-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the currently approved indications to include \"Treatment of adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL)\" with FIP1L1-PDGFRa rearrangements."}, {"id":"II/0032","type":"II","opinion":"2006-10-18","decision":"2006-11-28","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the current indication for the \"Treatment of adult patients with myelodysplastic/myeloproliferative diseases (MD/MPD) associated with PDGFR gene rearrangements\"."}, {"id":"R/0037","type":"R","opinion":"2006-07-27","decision":"2006-09-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0036","type":"II","opinion":"2006-07-27","decision":"2006-09-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Update of paediatric information in sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SPC on the basis of the data from the phase II clinical study (2108) in paediatric patients with CML, sponsored by the US NCI/COG."}, {"id":"II/0031","type":"II","opinion":"2006-07-27","decision":"2006-09-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Additional indication: \"Treatment of adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy and of adult patients with relapsed or refractory Ph+ ALL as monotherapy\"."}, {"id":"II/0030","type":"II","opinion":"2006-07-27","decision":"2006-09-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the current indication to include: \"Treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP)\"."}, {"id":"S/0029","type":"S","opinion":"2006-01-26","decision":"2006-03-20","affects":["SmPC","Annex II","Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0028","type":"II","opinion":"2006-01-26","decision":"2006-02-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Changes in the SPC section 4.8 in order to include 3 rare serious ADRs: aseptic necrosis of the bone, diverticulitis and gastrointestinal perforation following the 6th PSUR conclusions .The PL is updated accordingly."}, {"id":"II/0027","type":"II","opinion":"2006-01-26","decision":"2006-02-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of the SPC section 5.3 to reflect new animal carcinogenicity findings."}, {"id":"IB/0024","type":"IB","opinion":"2005-10-18","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0022","type":"II","opinion":"2005-05-26","decision":"2005-07-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the SPC and PL on safety and efficacy results from the clinical studies and post-marketing data relevant to the approved GIST indication."}, {"id":"II/0021","type":"II","opinion":"2005-05-26","decision":"2005-07-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the SPC and PL on safety and efficacy results from the clinical studies and post-marketing data relevant to the approved CML indication."}, {"id":"II/0020","type":"II","opinion":"2005-04-21","decision":"2005-06-02","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Revision of the SPC section 5.3 in order to include preclinical carcinogenicity findings."}, {"id":"S/0019","type":"S","opinion":"2005-01-20","decision":"2005-03-31","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"IB/0014","type":"IB","opinion":"2004-05-25","decision":"2004-05-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition of the following pack sizes: 90 x 400 mg film-coated tablets"}, {"id":"IB/0013","type":"IB","opinion":"2004-05-25","decision":"2004-05-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units outside range of appr. pack size"}, {"id":"IB/0012","type":"IB","opinion":"2004-05-25","decision":"2004-05-25","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition of the following pack size: 90 x 400 mg film-coated tablet."}, {"id":"N/0015","type":"N","opinion":"2004-05-14","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"S/0011","type":"S","opinion":"2004-01-21","decision":"2004-03-31","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"X/0007","type":"X","opinion":"2003-07-24","decision":"2003-11-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of a new pharmaceutical form; Addition of new strength"}, {"id":"X/0006","type":"X","opinion":"2003-07-24","decision":"2003-11-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of a new pharmaceutical form; Addition of new strength"}, {"id":"II/0008","type":"II","opinion":"2003-04-25","decision":"2003-07-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"S/0010","type":"S","opinion":"2003-03-19","decision":"2003-06-30","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annual re-assessment."}, {"id":"II/0004","type":"II","opinion":"2002-09-19","decision":"2002-12-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"II/0003","type":"II","opinion":"2002-09-19","decision":"2002-12-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"II/0002","type":"II","opinion":"2002-09-19","decision":"2002-12-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"II/0001","type":"II","opinion":"2002-02-21","decision":"2002-05-24","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"} ] }, "imetelstat__rytelo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/rytelo-epar-procedural-steps-taken-scientific-information-after-information_en.pdf"], "procedures": [] }, "imlunestrant__inluriyo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/inluriyo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000333242","type":"IAIN","opinion":"2026-02-20","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"E.4 Change in the name and/or address of the marketing Term name: E.4 authorisation holder, ASMF holder, storage site of the master and/or working cell bank, manufacturing site for an active substance, intermediate or finished product, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier - E.4.a) The change in the name and/or address concerns the marketing authorisation holder"} ] }, "inavolisib__itovebi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/itovebi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000309145","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Grouped application comprised of a Type II Variation and a Type IA Variation, as follows: Type II (C.I.4): Update of sections 4.2 and 5.2 of the SmPC in order to update posology recommendations for patients with severe renal impairment and to update pharmacokinetics information based on final results from study GP44944; this is a Phase I, open-label, multicenter, single-dose, parallel-group study to evaluate the effect of moderate or severe renal impairment on the pharmacokinetics, safety, and tolerability of a single oral dose of 6 mg inavolisib compared with demographically matched healthy subjects with normal renal function."}, {"id":"EMA/VR/0000312702","type":"IB","opinion":"2026-01-06","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d","B.II.f.1.b.z","B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the shelf-life or storage conditions of the finished product - Change in storage conditions of the finished product or the diluted/reconstituted product; Extension of the shelf life of the finished product - Other variation; Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Change in the holding time of an intermediate"} ] }, "inotuzumab-ozogamicin__besponsa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/besponsa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/besponsa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000278463","type":"IAIN","opinion":"2025-09-11","decision":"2026-05-06","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000257310","type":"II","opinion":"2026-03-26","decision":"2026-05-06","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include treatment of paediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL) for Besponsa, based on final results from studies ITCC-059 (WI203581) and INO-Ped-ALL-1 (WI235086). Study WI203581 is a Phase 1/2, multicenter, European, multi-cohort, open-label study in paediatric patients (≥1 and <18 years of age) with R/R CD22-positive ALL; Study WI235086 is an open-label, Phase 1 study to assess safety and tolerability of InO in Japanese paediatric patients with R/R CD22-positive AL. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 6.6 of the SmPC are updated."}, {"id":"II/0026","type":"II","opinion":"2023-12-14","decision":"2024-11-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.6","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.6, 4.8, 5.1 and 5.2 of the SmPC in order to update paediatric information based on final results from studies ITCC-059 (WI203581) and INO-Ped-ALL-1 (WI235086). Study WI203581 is a Phase 1/2, multicenter, European, multi-cohort, open-label study in pediatric patients (≥1 and <18 years of age) with R/R CD22-positive Acute Lymphoblastic Leukemia (ALL); and study WI235086 is an open-label, multi-center Phase 1 study to assess safety and tolerability of InO in Japanese pediatric patients with R/R CD22-positive ALL. The Package Leaflet is updated accordingly."}, {"id":"R/0023","type":"R","opinion":"2021-12-16","decision":"2022-02-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0019/G","type":"IB","opinion":"2020-10-16","decision":"2021-11-03","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.7","B.I.a.1.k","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - New storage site of MCB and/or WCB; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0022","type":"IAIN","opinion":"2021-05-31","decision":"2021-11-03","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"N/0015","type":"N","opinion":"2019-11-13","decision":"2020-07-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0011","type":"IB","opinion":"2019-08-21","decision":"2020-07-23","affects":["SmPC","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IAIN/0016","type":"IAIN","opinion":"2019-12-11","decision":"2020-07-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0006","type":"II","opinion":"2018-07-26","decision":"2019-07-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2","5.3","6.6"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC based on the supplemental Clinical Study Report for the pivotal phase 3 Study B1931022 (Study 1022) that was prepared following last patient last visit. The Package Leaflet is updated accordingly. The MAH took the opportunity to make minor editorial changes for added clarity in sections 4.2, 4.4, 4.8, 5.1, 5.3 and 6.6 of the SmPC and Package Leaflet."}, {"id":"IB/0008/G","type":"IB","opinion":"2018-10-05","decision":"2019-07-19","affects":["SmPC","Annex II","PL"],"codes":["A.4","A.5.b","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"T/0007","type":"T","opinion":"2018-07-11","decision":"2018-07-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0002","type":"N","opinion":"2017-12-05","decision":"2018-07-26","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0001/G","type":"IA","opinion":"2017-10-30","decision":"2018-07-26","affects":["Annex II"],"codes":["A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"} ] }, "ipilimumab__yervoy": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/yervoy-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/yervoy-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000319172","type":"II","opinion":"2026-05-07","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add 'Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome' to the table of Recommended treatment modifications, to the special warnings and to the list of adverse drug reactions (ADRs)"}, {"id":"EMA/VR/0000285155","type":"IB","opinion":"2025-11-13","decision":null,"affects":["Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To extend the due date related to the PAES study CA2098Y8, listed in the Product Information (PI) Annex II and in the RMP from 28.02.2026 to 28.02.2027. In addition, the MAH included the list of local representatives in the labelling for Yervoy."}, {"id":"WS/2717","type":"WS","opinion":"2025-01-30","decision":"2025-02-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include a new indication for OPDIVO in combination with ipilimumab as first line treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC) based on study CA2099DW. This is a phase 3 randomised, multi-centre, open label study of Nivolumab in combination with Ipilimumab compared to Sorafenib or Lenvatinib as first-line treatment in participants with advanced HCC. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 41.1 of the RMP has also been submitted."}, {"id":"WS/2672","type":"WS","opinion":"2024-11-14","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.6"],"scope":"Extension of indication to include OPDIVO in combination with ipilimumab in the first-line treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) unresectable or metastatic colorectal cancer, based on interim results from study CA2098HW; this is a phase 3 randomised clinical trial of nivolumab alone, nivolumab in combination with ipilimumab, or investigator’s choice chemotherapy in participants with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"WS/2597","type":"WS","opinion":"2024-02-15","decision":"2024-09-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to add ‘myelitis’ as a warning under the subsection “Other immune-mediated adverse reactions” and to the list of adverse drug reactions (ADRs) with their calculated frequencies for monotherapy (not known) and in combination (rare), based on post marketing data and literature; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to the SmPC in line with the QRD."}, {"id":"IB/0112","type":"IB","opinion":"2024-06-28","decision":"2024-09-27","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0113/G","type":"IAIN","opinion":"2024-06-24","decision":"2024-09-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0106","type":"IAIN","opinion":"2023-10-13","decision":"2024-09-27","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0100","type":"II","opinion":"2023-04-26","decision":"2023-05-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with nivolumab the treatment of adolescents (12 years of age and older) for advanced (unresectable or metastatic) melanoma, based on the pivotal study CA209070; this is a multicentre, open-label, single arm, phase 1/2 trial of nivolumab +/- ipilimumab in children, adolescents and young adults with recurrent or refractory solid tumours or lymphomas. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 38.0 of the RMP has also been submitted."}, {"id":"WS/2289","type":"WS","opinion":"2022-09-01","decision":"2023-04-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update sections 4.8 and 5.1 of the SmPC to include 7.5 years of minimum follow-up for all subjects based on addendum 04 Clinical Study Report for Study CA209067; this is a phase 3 randomized, double-blind study of nivolumab monotherapy or nivolumab in combination with ipilimumab versus ipilimumab monotherapy in subjects with previously untreated, unresectable melanoma. MAH has taken the opportunity to introduce minor editorial revisions in the SmPC."}, {"id":"WS/2187","type":"WS","opinion":"2022-10-27","decision":"2023-04-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in alignment with the recommendations made by the CHMP to revise the pooling approach used to describe irARs and tabulated summaries of ADRs following II/0096. Individual study data included within this application has been previously reviewed by the CHMP. The updated Opdivo RMP version 29.0 and Yervoy RMP version 37.0 have also been submitted. The MAH took the opportunity to introduce editorial changes. The Package Leaflet was updated accordingly."}, {"id":"IB/0104","type":"IB","opinion":"2023-03-21","decision":"2023-04-24","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0097","type":"IB","opinion":"2022-04-22","decision":"2023-04-24","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update Annex II of the PI with revised due date related to a PAES study."}, {"id":"IA/0103","type":"IA","opinion":"2023-02-14","decision":"2023-04-24","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"WS/2170","type":"WS","opinion":"2022-01-13","decision":"2022-04-01","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 and 5.1 of the SmPC in order to update efficacy information based on 5 years follow-up OS data from study CA209214; this is a phase 3, randomised, open-label study in previously untreated, intermediate/poor risk advanced RCC."}, {"id":"WS/2153","type":"WS","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"Update of sections 4.2 and 6.6 of the SmPC to change the infusion time for ipilimumab at a dose of 3 mg/kg from 90 minutes to 30 minutes when used as monotherapy or in combination with nivolumab in the melanoma indications."}, {"id":"WS/2113","type":"WS","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) with tumour cell PD-L1 expression ≥ 1% for Opdivo in combination with Yervoy; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 26.2 of the Opdivo RMP and version 35.0 of the Yervoy RMP have also been submitted."}, {"id":"IAIN/0096/G","type":"IAIN","opinion":"2022-02-17","decision":"2022-04-01","affects":["SmPC","Annex II","PL"],"codes":["A.5.a","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"WS/2134","type":"WS","opinion":"2021-10-28","decision":"2022-01-07","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8, and 5.1 of the SmPC following based on final results from study CA209908; this is a Phase Ib/II clinical trial of nivolumab monotherapy and nivolumab in combination with ipilimumab in paediatric subjects with high grade primary CNS malignancies; The RMP version 22.4 for Opdivo has also been submitted."}, {"id":"WS/2043","type":"WS","opinion":"2021-06-10","decision":"2022-01-07","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00009200/202103","type":"PSUSA","opinion":"2021-11-11","decision":"2022-01-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"IAIN/0092","type":"IAIN","opinion":"2021-08-26","decision":"2022-01-07","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/1840","type":"WS","opinion":"2021-05-20","decision":"2021-06-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the combination of nivolumab with ipilimumab in the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability_high (MSI-H) metastatic colorectal cancer (CRC) after prior fluoropyrimidine based combination chemotherapy; as a consequence, sections 4.1, 4.2 ,4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 20.2 for Opdivo and version 30.2 for Yervoy of the RMP have also been submitted."}, {"id":"WS/1881","type":"WS","opinion":"2021-04-22","decision":"2021-06-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM) for combination treatment of Opdivo and Yervoy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 (for both products) and 6.6 (for Opdivo) of the SmPC are updated. The Package Leaflet is updated in accordance. Version 20.1 for Opdivo and version 30.1 for Yervoy of the RMP has also been adopted."}, {"id":"PSUSA/00009200/202003","type":"PSUSA","opinion":"2020-11-12","decision":"2021-01-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"WS/1790","type":"WS","opinion":"2020-07-23","decision":"2020-11-05","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to include at least 5 years (60 months) of follow-up for all subjects from study CA209067. Updated efficacy data provided in this submission include overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)."}, {"id":"WS/1783","type":"WS","opinion":"2020-09-17","decision":"2020-11-05","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include first-line treatment of metastatic non-small cell lung cancer in adults whose tumours have no sensitising EGFR mutation or ALK translocation for combination of OPDIVO/Yervoy and chemotherapy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 17.1 of the RMP for OPDIVO and version 28.1 for Yervoy have also been submitted."}, {"id":"II/0080","type":"II","opinion":"2020-07-09","decision":"2020-11-05","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of an updated RMP version 28.0 in order to propose the discontinuation of the Healthcare Professional Adverse Reaction Management Guide as an additional risk minimization measure described in the RMP Annex 6 and in the Product Information Annex II.D. The RMP and the annex II.D are updated accordingly. The MAH also took the occasion to align the PI to the latest QRD version 10.1 and to include standard text on sodium excipient information."}, {"id":"IAIN/0079","type":"IAIN","opinion":"2020-05-11","decision":"2020-11-05","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"WS/1714","type":"WS","opinion":"2019-12-12","decision":"2020-01-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to update the safety information on myocarditis management for nivolumab monotherapy or for nivolumab in combination with ipilimumab therapy."}, {"id":"PSUSA/00009200/201903","type":"PSUSA","opinion":"2019-10-17","decision":"2019-12-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"N/0071","type":"N","opinion":"2019-07-31","decision":"2019-12-17","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0064","type":"II","opinion":"2019-10-03","decision":"2019-12-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to add stomatitis to the list of ADRs with a frequency uncommon, to further explain the components of the existing ADR musculoskeletal pain in a footnote and to update safety information based on final results from study CA184143 (A Multi-National, Prospective, Observational Study in Patients with Unresectable or Metastatic Melanoma) listed as a category 3 study in the RMP (MEA017.11); the Package Leaflet and the RMP have been updated accordingly (version 26.2)."}, {"id":"IG/1059","type":"IG","opinion":"2019-02-15","decision":"2019-04-02","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"IAIN/0062","type":"IAIN","opinion":"2018-11-22","decision":"2019-04-02","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/1278","type":"WS","opinion":"2018-11-15","decision":"2019-01-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the combination treatment with nivolumab and ipilimumab of adult patients with intermediate/poor-risk advanced renal cell carcinoma. As a consequence sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the Opdivo and Yervoy SmPCs were proposed to be updated. The Package Leaflet and the Risk Management Plan (version 19.0 for Yervoy and version 13.0 for Opdivo) were proposed to be updated in accordance. In addition, the Worksharing applicant (WSA) would take the opportunity to correct some typos throughout the Yervoy and Opdivo product information."}, {"id":"II/0058/G","type":"II","opinion":"2018-09-13","decision":"2019-01-11","affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.b","B.II.b.2.c.3","B.II.d.2.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated to include Swords Laboratories T/A Bristol-Myers Squibb Cruiserath Biologics, Cruiserath Road Mulhudarft, Dublin 15 Ireland as an alternative batch release site. The PL has also been updated to include the site as alternative manufacturing site."}, {"id":"II/0054","type":"II","opinion":"2018-06-14","decision":"2019-01-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to update the overall survival data of ipilimumab 3mg/kg monotherapy pooled across studies based on the final results of studies CA184332 and CA184338 listed as category 3 studies in the RMP, in order to fulfil MEA 035 and MEA 030.1 respectively. Study CA184332 is a multi-site retrospective observational study of US patients with unresectable or metastatic melanoma receiving ipilimumab as first line therapy in a community practice setting and study CA184438 is a multi-site retrospective observational study of US patients with unresectable or metastatic melanoma receiving ipilimumab as first line therapy."}, {"id":"II/0055","type":"II","opinion":"2018-04-26","decision":"2018-05-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of advanced (unresectable or metastatic) melanoma in adults in combination with nivolumab for Yervoy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and the RMP (version 20.1) are updated in accordance. In addition, the Marketing Authorisation Holder (MAH) took the opportunity to update the contact details of the Irish local representative in the Package Leaflet."}, {"id":"II/0044","type":"II","opinion":"2017-12-14","decision":"2018-01-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older for Yervoy. As a consequence sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and the RMP (version 15) are updated in accordance."}, {"id":"PSUSA/00009200/201703","type":"PSUSA","opinion":"2017-11-09","decision":"2018-01-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"II/0047/G","type":"II","opinion":"2017-09-01","decision":"2018-01-08","affects":["SmPC"],"codes":["C.I.4","C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of section 4.4 to revise the current warning on concurrent administration with vemurafenib to enhance awareness on the potential of hypersensitivity reactions when ipilimumab is used sequentially with vemurafenib as requested by the PRAC following the assessment of PSUSA/00009200/201603. Update of sections 4.8 of the SmPC to amend the frequency of the adverse drug reaction ‘Vogt-Konyanagi-Haranda syndrome’ from ‘not known’ to ‘rare’. The Package Leaflet and RMP (version 16.1) have been updated accordingly."}, {"id":"II/0042","type":"II","opinion":"2017-11-09","decision":"2018-01-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC to reflect the final results of study CA184-169, a randomized double-blind phase III study of ipilimumab administered at 3 mg/kg versus at 10 mg/kg in subjects previously treated or untreated with unresectable or metastatic melanoma, in order to fulfil ANX 014.1. The MAH also provided with this variation application efficacy and safety data from study CA184-169 in two subgroups: female ≥ 50 years of age and with brain metastases in order to fulfil MEA 015.1. Annex II.D and the RMP (version 14.1) are updated accordingly."}, {"id":"N/0039","type":"N","opinion":"2016-05-18","decision":"2017-05-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0036/G","type":"II","opinion":"2016-06-23","decision":"2017-05-31","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.a.1.k","B.I.a.4.z","B.II.b.1.c","B.II.b.4.f","B.II.e.1.b.2","B.III.2.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - New storage site of MCB and/or WCB; Change to in-process tests or limits applied during the manufacture of the AS - Other variation."}, {"id":"IAIN/0041","type":"IAIN","opinion":"2016-11-30","decision":"2017-05-31","affects":["SmPC","PL"],"codes":["C.I.12"],"outcome":"accepted","kind":"other","sections":[],"scope":"Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring"}, {"id":"IA/0046","type":"IA","opinion":"2017-03-31","decision":"2017-05-31","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"R/0035","type":"R","opinion":"2016-02-25","decision":"2016-04-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0037","type":"N","opinion":"2015-11-18","decision":"2016-04-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00009200/201503","type":"PSUSA","opinion":"2015-10-22","decision":"2015-12-14","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"II/0028/G","type":"II","opinion":"2015-04-23","decision":"2015-12-14","affects":["Annex II"],"codes":["B.I.a.2.c","B.I.a.1.e","B.I.a.1.f","B.I.b.1.f","B.I.b.2.d","B.I.b.2.e","B.II.b.1.c","B.II.b.3.a","B.II.b.4.f","B.II.d.1.e","B.II.f.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - The change refers to a [-] substance in the manufacture of a biological/immunological substance which may have a significant impact on the medicinal product and is not related to a protocol; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place."}, {"id":"PSUSA/00009200/201409","type":"PSUSA","opinion":"2015-04-23","decision":"2015-06-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ipilimumab"}, {"id":"II/0029","type":"II","opinion":"2015-03-26","decision":"2015-06-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to revise the description of mechanism of action in the Yervoy (ipilimumab). The requested variation leads to amendments to the Summary of Product Characteristics."}, {"id":"II/0027","type":"II","opinion":"2014-09-25","decision":"2015-06-19","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Change(s) with new additional data submitted by the MAH"}, {"id":"II/0026/G","type":"II","opinion":"2014-09-25","decision":"2015-06-19","affects":["SmPC"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUV/0020","type":"PSUV","opinion":"2013-10-24","decision":"2013-12-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0014","type":"II","opinion":"2013-05-30","decision":"2013-10-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to add a warning with regard to the combined use of ipilimumab and vemurafenib at the request of the CHMP following information on results of a clinical trial. The Package leaflet has been updated accordingly. The product information has also been updated in line with QRD template version 9 and the list of local representatives in the package leaflet has been revised to add the contact in Croatia."}, {"id":"II/0008","type":"II","opinion":"2013-10-24","decision":"2013-10-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1","5.2"],"scope":"Extension of indication of Yervoy for the treatment of previously untreated adult patients with advanced (unresectable or metastatic) melanoma. Consequently, sections 4.1, 4.2, 4.5, 4.8, 5.1 and 5.2 of the Summary of Product Characteristics (SmPC) have been updated. The Package Leaflet has been updated accordingly. Editorial changes were also made to the SmPC and Package Leaflet."}, {"id":"II/0002","type":"II","opinion":"2012-05-24","decision":"2012-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC with the results of a pre- and post-natal development study in cynomolgus monkeys conducted at the request of the CHMP (FUM 013). The MAH also took the opportunity to update the product information in line with the QRD template version 8.1 and to make minor corrections to the SmPC."}, {"id":"II/0001","type":"II","opinion":"2012-03-15","decision":"2012-04-26","affects":["Annex II"],"codes":["B.I.b.2.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"To replace the current method used to determine host cell protein (HCP) levels in unformulated bulk drug substance by a new process specific HCP method. This type II variation addresses Quality Obligation 001."} ] }, "isatuximab__sarclisa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/sarclisa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"II/0035","type":"II","opinion":"2025-06-19","decision":"2025-07-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include, in combination with bortezomib, lenalidomide and dexamethasone, the induction treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant (ASCT) for SARCLISA, based on the results from study IIT15403 (GMMG-HD7); this is a randomised phase III study designed to assess the efficacy and safety of Sarclisa for the induction and maintenance treatment of NDMM. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI."}, {"id":"R/0033","type":"R","opinion":"2024-12-12","decision":"2025-02-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0032","type":"N","opinion":"2024-07-24","decision":"2025-01-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0030","type":"II","opinion":"2024-11-14","decision":"2025-01-20","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.7","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with bortezomib, lenalidomide, and dexamethasone the treatment of adult patients with newly diagnosed active multiple myeloma who are not eligible for autologous stem cell transplant (ASCT) for Sarclisa, based on results from EFC12522 (IMROZ) pivotal phase III study and the supportive TCD13983 phase 1b/2 study. EFC12522 is an ongoing prospective, multicenter, international, randomized, open-label, 2-arm parallel group study to assess the clinical benefit of VRd (control group) versus IVRd (active group) for the treatment of participants with NDMM who are not eligible for ASCT. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.7, 4.8, 5.1 and 5."}, {"id":"II/0028","type":"II","opinion":"2024-04-04","decision":"2025-01-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to update information on paediatric population based on final results from study ACT15378 (ISAKIDS). This was a Phase 2, single-arm, multicenter, open-label study evaluating the antitumor activity, safety, and PK of isatuximab in combination with standard salvage chemotherapies in paediatric participants with R/R ALL (including both T-ALL and B-ALL) and AML conducted in 3 separate cohorts. Male and female children from 28 days to less than 18 years of age with R/R T-ALL, B-ALL, or AML in first or second relapse were eligible."}, {"id":"II/0027","type":"II","opinion":"2024-04-11","decision":"2025-01-20","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Thrombocytopenia’ and ‘Anaemia’ to the list of adverse drug reactions (ADRs) and to amend the frequency of all remaining ADRs with their appropriate frequencies, following PRAC request in the outcome of the PSUSA procedure PSUSA/00010851/202303."}, {"id":"II/0026","type":"II","opinion":"2024-02-22","decision":"2025-01-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC based on final results from study TED16414, listed as a category 3 study in the RMP; this is a phase 1b/2 open label, non-randomized, multi center study to evaluate the safety, pharmacokinetics, and preliminary efficacy of isatuximab (SAR650984) in patients awaiting kidney transplantation. The Package Leaflet is updated accordingly. The RMP version 1.6 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0025","type":"II","opinion":"2024-04-11","decision":"2025-01-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to amend an existing warning on second primary malignancies and to update efficacy and safety information based on Overall Survival analysis from study EFC15246 (IKEMA - Randomized, open label, multicenter study assessing the clinical benefit of isatuximab combined with carfilzomib (Kyprolis) and dexamethasone versus carfilzomib with dexamethasone in patients with relapsed and/or refractory multiple myeloma previously treated with 1 to 3 prior lines). In addition, the MAH took this opportunity to introduce editorial changes to the PI."}, {"id":"N/0022","type":"N","opinion":"2023-06-29","decision":"2024-02-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0020","type":"II","opinion":"2023-03-30","decision":"2024-02-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to update an existing warning on ‘second primary malignancies’, update the list of adverse drug reactions (ADRs) and update the efficacy and safety information based on final OS analysis from ICARIA study (EFC14335), following a recommendation by the CHMP during the initial MAA. This is a phase 3 randomized, open-label, multicenter study designed to assess the efficacy, safety, and pharmacokinetics (PK) of isatuximab in combination with pomalidomide and low-dose dexamethasone (IPd) compared with pomalidomide and low-dose dexamethasone (Pd) in patients with refractory or relapsed and refractory multiple myeloma."}, {"id":"II/0018/G","type":"II","opinion":"2022-12-15","decision":"2024-02-16","affects":["SmPC"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1","5.2"],"scope":"Update of sections 4.5, 5.1 and 5.2 of the SmPC in order to update the efficacy and pharmacokinetic data based on final progression-free survival (PFS) efficacy results from IKEMA study (EFC15246) and to introduce the Sebia Hydrashift assay, a validated assay to determine the complete response rate. IKEMA study (EFC15246) is a phase 3 randomized, open label, multicenter study assessing the clinical benefit of isatuximab combined with carfilzomib (Kyprolis) and dexamethasone versus carfilzomib with dexamethasone in patients with relapsed and/or refractory multiple myeloma previously treated with 1 to 3 prior lines."}, {"id":"II/0017/G","type":"II","opinion":"2022-12-15","decision":"2024-02-16","affects":["Annex II"],"codes":["B.I.b.1.z","B.I.a.3.c","B.I.a.2.c","B.I.a.1.j","B.I.a.1.k","B.I.a.4.d","B.I.a.1.e","B.II.b.5.z","B.I.b.2.d","B.I.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of an AS, starting material/intermediate/reagent - Other variation; Change in batch size (including batch size ranges) of AS or intermediate - The change requires assessment of the comparability of a biological/immunological AS; Changes in the manufacturing process of the AS - The change refers to a [-] substance in the manufacture of a biological/immunological substance which may have a significant impact on the medicinal product and is not related to a protocol."}, {"id":"T/0019","type":"T","opinion":"2022-10-28","decision":"2022-12-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00010851/202203","type":"PSUSA","opinion":"2022-10-13","decision":"2022-12-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - isatuximab"}, {"id":"N/0011","type":"N","opinion":"2021-11-09","decision":"2022-12-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0014","type":"II","opinion":"2022-06-02","decision":"2022-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to amend an existing warning on Infections by adding herpes zoster prophylaxis as antiviral prophylaxis, following FDA post-market survey and request to update the US PI based on a cumulative assessment of Sanofi global PV database and scientific literature. The Package Leaflet is updated accordingly. is recommended for approval."}, {"id":"PSUSA/00010851/202009","type":"PSUSA","opinion":"2021-04-22","decision":"2021-06-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - isatuximab"}, {"id":"II/0003","type":"II","opinion":"2021-02-25","decision":"2021-04-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","4.9","5.1","5.2","6.3","6.6"],"scope":"An Extension of indication for Sarclisa to add combination with carfilzomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. As a consequence the sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 have been updated. The PL is updated accordingly. The MAH took the opportunity to introduce minor changes in the SmPC sections 4.9, 6.3 and 6.6 and update the details of local representatives. Editorial changes have been also introduced to the Annex II key elements of the RMMs. The RMP version 1.2 has been updated."} ] }, "ivosidenib__tibsovo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tibsovo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tibsovo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000316586","type":"IB","opinion":"2026-02-24","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.1"],"scope":"To change ATC level name from 'Antineoplastic agents; other antineoplastic agents' to 'Antineoplastic agents; isocitrate dehydrogenase (IDH) inhibitors' in Section 5.1 of the Summary of Product Characteristics (SmPC), as per WHO request and to change the ATC Code from L01XM62 to L01XM02. To update SmPC section 4.2 to provide clear and precise guidance on administration and to enhance the comprehension and correct usage of the medication by HCPs posology of TIBSOVO for the treatment of Acute Myeloid Leukemia (AML) . To update section 4.5 of the SmPC to include atazanavir as an example of a drug– drug interaction with Ivosidenib."}, {"id":"N/0009","type":"N","opinion":"2024-08-02","decision":"2024-12-12","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0004","type":"IB","opinion":"2023-12-22","decision":"2024-12-12","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "ixazomib__ninlaro": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ninlaro-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ninlaro-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000334802","type":"II","opinion":"2026-05-21","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on haemolytic uremic syndrome based on post-marketing data and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial updates to the PI, to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template version 10.4."}, {"id":"IB/0048","type":"IB","opinion":"2024-09-10","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.e.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in container closure system of the Finished Product - Other variation"}, {"id":"PSUSA/00010535/202311","type":"PSUSA","opinion":"2024-06-27","decision":"2024-08-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ixazomib PSUSA/10535/202311."}, {"id":"PSUSA/00010535/202305","type":"PSUSA","opinion":"2024-01-25","decision":"2024-03-19","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ixazomib"}, {"id":"II/0045","type":"II","opinion":"2023-09-14","decision":"2023-11-03","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the Clinical Study Report (Addendum 2) for study C16019 listed as a Specific Obligation in the Annex II of the Product Information. This is a phase 3, randomized, double-blind, placebo-controlled study of single-agent oral ixazomib as maintenance therapy following autologous stem cell transplant (ASCT) for patients with newly diagnosed multiple myeloma. In addition, the MAH proposes to remove NINLARO from the list of medicines subject to additional monitoring and to remove the black triangle from the SmPC. The Annex II and Package Leaflet are updated accordingly. The RMP version 10.0 has also been submitted."}, {"id":"IB/0044/G","type":"IB","opinion":"2023-08-23","decision":"2023-10-05","affects":["Annex II","PL"],"codes":["B.I.a.4.z","B.I.b.2.c","B.I.a.1.f","B.I.a.2.a","B.I.a.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Other variation"}, {"id":"II/0041","type":"II","opinion":"2023-01-12","decision":"2023-09-01","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study NSMM-5001 (INSIGHT) listed as a Specific Obligation in the Annex II of the Product Information. This is a global, prospective, non-interventional, observational study of presentation, treatment patterns, and outcomes in multiple myeloma patients. The Annex II and the RMP (submitted version 9.0) are updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0033","type":"II","opinion":"2021-12-02","decision":"2022-09-13","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Submission of the final report for the final analysis of OS for study C16010 fulfilling an obligation in the Annex II of the Product Information. This is a phase 3 study to evaluate efficacy and safety of ixazomib in combination with LenDex in adult patients with relapsed and/or refractory multiple myeloma. Section 4.4 is also updated to include a warning about occurrence of Stevens-Johnson syndrome. The Package Leaflet is updated accordingly. An updated RMP (version 7.0) has been submitted. The applicant also took the opportunity to update the list of local representatives. 1is recommended for approval."}, {"id":"IB/0039","type":"IB","opinion":"2022-06-16","decision":"2022-09-13","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"R/0030","type":"R","opinion":"2021-09-16","decision":"2021-11-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0026","type":"II","opinion":"2021-03-11","decision":"2021-11-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of Annex II of the Product Information and the Risk Management Plan v. 5.1 following the completion of study C16014 comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in adult patients with newly diagnosed multiple myeloma not eligible for stem cell transplantation (SCT) in fulfilment of SOB 003. A minor editorial change is proposed to section 4.2 Posology and Method of administration, for consistency with other sections of the SmPC. In addition, an update is proposed to the local representatives information in the Package Leaflet."}, {"id":"II/0025","type":"II","opinion":"2021-01-21","decision":"2021-11-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.9"],"scope":"Update of the SmPC section 4.9 with additional information on Ninlaro overdose. The Package leaflet is updated accordingly."}, {"id":"II/0022","type":"II","opinion":"2020-11-12","decision":"2021-11-12","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update section 4.8 undesirable effects of the Ninlaro (Ixazomib) Summary of Product Characteristics (SmPC) following the adoption of the CHMP opinion in 25 June 2020 on PSUR assessment procedure EMEA/H/C/PSUSA/00010535/201911. Consequently the ADRs: acute febrile neutrophilic dermatosis, Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy disorders and tumour lysis syndrome have been assigned frequency rare."}, {"id":"IB/0032","type":"IB","opinion":"2021-06-28","decision":"2021-11-12","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IA/0029/G","type":"IA","opinion":"2021-04-12","decision":"2021-11-12","affects":["SmPC","Annex II","PL"],"codes":["A.7","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0021","type":"R","opinion":"2020-09-17","decision":"2020-11-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0024","type":"IAIN","opinion":"2020-09-09","decision":"2020-11-20","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUSA/00010535/201911","type":"PSUSA","opinion":"2020-06-25","decision":"2020-08-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ixazomib"}, {"id":"II/0019/G","type":"II","opinion":"2020-06-25","decision":"2020-08-25","affects":["Annex II"],"codes":["C.I.11.b","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Group of variations consisting of the: C.I.11.b: Submission of the final report from study NSMM-5001 listed as a Specific Obligation in the Annex II of the Product Information. This is a global, prospective, non-interventional, observational study in multiple myeloma patients. The Annex II and the RMP (submitted version 5) are updated accordingly. C.I.11.z: Submission of an updated RMP version 5 in order to extend the due date of the Post-authorisation efficacy study (PAES) C16010 listed in Annex IID. The MAH also took the opportunity to correct a typographical error in Annex II."}, {"id":"IAIN/0018/G","type":"IAIN","opinion":"2019-08-19","decision":"2020-08-25","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","B.I.a.1.f"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place"}, {"id":"II/0014/G","type":"II","opinion":"2019-07-25","decision":"2019-09-16","affects":["Annex II"],"codes":["C.I.11.b","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Group of variations consisting of a type 2 variation to include submission of final report of progression free survival (PFS) in fulfilment of SOB 004 and a type IB variation to request and extension of the due date of SOB 003. The Annex II is amended accordingly. Consequently, the RMP is updated (version 4.2). In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce minor editorial changes throughout the PI and to bring the PI in line with the latest QRD template version 10.1."}, {"id":"R/0012","type":"R","opinion":"2018-07-26","decision":"2018-09-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0007","type":"IB","opinion":"2017-12-12","decision":"2018-07-06","affects":["SmPC","Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0004","type":"IAIN","opinion":"2017-07-18","decision":"2018-07-06","affects":["SmPC","PL"],"codes":["B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"R/0003","type":"R","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","Annex II","Labelling"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0002","type":"II","opinion":"2017-07-06","decision":"2017-09-18","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to reflect the final overall survival analysis of C16010 China continuation study, a phase III study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma, in order to fulfil SOB (Specific Obligation) 002. Annex II.E and the RMP (version 2.1) are updated accordingly. In addition the Marketing Authorisation Holder (MAH) took the opportunity to include the date of marketing authorisation in section 9 of the SmPC, to make a small correction in the Product Information to the Finnish, German and Swedish translations."} ] }, "lapatinib__tyverb": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tyverb-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tyverb-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000320526","type":"IA","opinion":"2026-01-05","decision":null,"affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000291894","type":"IAIN","opinion":"2025-08-21","decision":null,"affects":["Annex II","PL"],"codes":["A.5.a","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)"}, {"id":"IAIN/0081/G","type":"IAIN","opinion":"2024-12-11","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0080","type":"IAIN","opinion":"2024-10-07","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0076/G","type":"IAIN","opinion":"2023-05-10","decision":"2024-05-10","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"II/0072/G","type":"II","opinion":"2022-01-13","decision":"2023-01-30","affects":["SmPC","PL"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add skin fissures to the list of adverse drug reactions (ADRs) with frequency common, following recently analyzed safety data regarding skin fissures. The Package Leaflet is updated accordingly. The ATC code is also updated."}, {"id":"N/0070","type":"N","opinion":"2021-09-07","decision":"2021-10-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0067","type":"IB","opinion":"2020-10-26","decision":"2021-10-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0065/G","type":"IA","opinion":"2019-09-16","decision":"2020-09-17","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"R/0060","type":"R","opinion":"2019-07-25","decision":"2019-09-19","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0062","type":"II","opinion":"2019-07-11","decision":"2019-09-19","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0057","type":"II","opinion":"2018-12-13","decision":"2019-05-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC in order to update the safety information on pregnancy and breast-feeding following review of the company Core Data Sheet (CDS). The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives for Estonia and Lithuania in the Package Leaflet. Moreover, the MAH took the opportunity to make minor editorial changes in the Labelling of the bottle presentations."}, {"id":"IB/0061","type":"IB","opinion":"2019-04-26","decision":"2019-05-22","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0056","type":"IAIN","opinion":"2018-07-25","decision":"2019-05-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0051","type":"II","opinion":"2018-06-28","decision":"2018-07-30","affects":["SmPC","Annex II"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","5.1"],"scope":"Update of sections 4.1, 4.4 and 5.1 of the SmPC based on results from study EGF114299/LAP016A2307 listed as a condition (ANX027.4) in the Annex II; a Phase III trial to compare the safety and efficacy of lapatinib plus trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI versus lapatinib plus an AI as first- or second-line therapy in postmenopausal subjects with hormone receptor positive, HER2-positive metastatic breast cancer (MBC) who have received prior trastuzumab and endocrine therapies. Annex II has been updated accordingly. A revised RMP version 35.1 has also been approved."}, {"id":"IB/0055","type":"IB","opinion":"2018-06-20","decision":"2018-07-30","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"T/0052","type":"T","opinion":"2018-04-04","decision":"2018-05-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0050/G","type":"II","opinion":"2018-01-25","decision":"2018-05-22","affects":["Annex II"],"codes":["C.I.13","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of the final non-clinical study report 09DMR047 listed as a category 3 study in the RMP. This is a non-clinical mechanistic study related to lapatinib metabolite identification in dog plasma, bile and liver. An updated RMP (version 33.0) is included to reflect the completion of a dog study and integration of the results. Change to the final due date of study EGF117165 to evaluate biomarkers of drug resistance in patients with HER2+ metastatic breast cancer whilst on treatment with trastuzumab in combination with either lapatinib or chemotherapy (category 1, ANX034.2) from June 2018 to June 2019 in Annex II and the RMP."}, {"id":"II/0048/G","type":"II","opinion":"2017-07-20","decision":"2018-05-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH updated the SmPC in order to: - add in section 4.4 a warning on concentration-dependent increase of the QTc interval, concomitant use of CYP3A4 inhibitors, and a strengthened recommendation of ECG monitoring (), - to add to the tabulated list of adverse reactions in section 4.8 Ventricular arrhythmias/Torsades de Pointes, electrocardiogram QT prolonged (frequency Not known)"}, {"id":"II/0041/G","type":"II","opinion":"2015-06-25","decision":"2016-06-29","affects":["Annex II"],"codes":["C.I.11.b","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of a revised RMP in order to include general updates in the RMP regarding posology update, addition of some new studies to Pharmacovigilance Activities and addition of details of three newly available study reports; timelines have been also changed for study EGF114299 and study EGF117165 and RMP (final version adopted is v29.0) and annex II have been updated accordingly."}, {"id":"IAIN/0045/G","type":"IAIN","opinion":"2015-07-13","decision":"2016-06-29","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00001829/201409","type":"PSUSA","opinion":"2015-04-23","decision":"2015-06-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lapatinib"}, {"id":"T/0043","type":"T","opinion":"2015-03-30","decision":"2015-05-05","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation from Glaxo Group Ltd. to Novartis Europharm Limited. Transfer of Marketing Authorisation"}, {"id":"II/0037","type":"II","opinion":"2014-12-18","decision":"2015-02-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with information on lapatinib effect on CNS metastasis further to comparative data on the incidence of CNS metastases from studies EGF108919 (COMPLETE), EGF105485 (TEACH) and EGF106708 (ALTTO) (SOB 002.4). Annex II is also updated further to the fulfilment of the specific obligation."}, {"id":"II/0038","type":"II","opinion":"2014-12-18","decision":"2015-02-11","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC further to disease-free survival (DFS) results from hormone receptor-positive patients in the adjuvant EGF106708 (ALTTO) study (REC 037)."}, {"id":"II/0033","type":"II","opinion":"2014-07-24","decision":"2015-02-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"R/0030","type":"R","opinion":"2014-01-23","decision":"2014-03-12","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0022","type":"II","opinion":"2013-06-27","decision":"2013-07-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include treatment for adult patients with breast cancer whose tumours overexpress HER2 (ErbB2), in combination with trastuzumab for patients with hormone receptor-negative metastatic disease, that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy. As a consequence sections 4.1, 4.2, 4.8 and 5.1 of the SmPC have been updated. The Package Leaflet is updated accordingly. Changes were also made to the PI to bring it in line with the QRD template version 9 and make minor corrections. In addition, the list of local representatives in the PL is revised to add contact details for the representative of Croatia."}, {"id":"IG/0279","type":"IG","opinion":"2013-04-18","decision":"2013-07-25","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"R/0028","type":"R","opinion":"2013-02-21","decision":"2013-04-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0027","type":"II","opinion":"2012-11-15","decision":"2013-04-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on results from interim analyses of two phase III studies which compared lapatinib and trastuzumab in combination with chemotherapy in women with advanced or metastatic breast cancer. The Package leaflet is updated accordingly."}, {"id":"II/0026","type":"II","opinion":"2012-12-13","decision":"2013-04-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information regarding hepatotoxicity with the results of a pharmacogenetic analysis from study EGF114471, a sub-study of EGF105485 (TEACH)."}, {"id":"II/0024","type":"II","opinion":"2012-06-21","decision":"2012-07-31","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1","5.2"],"scope":"Update of SmPC sections 4.5, 5.1 and 5.2 with information on the variability in exposure depending on when lapatinib is administered in relation to food intake as requested by CHMP following the assessment of FU2 007.1."}, {"id":"IAIN/0025","type":"IAIN","opinion":"2012-05-23","decision":"2012-07-31","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"IA/0018/G","type":"IA","opinion":"2011-07-15","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.1.b","B.II.b.1.a","B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"II/0016","type":"II","opinion":"2011-04-14","decision":"2011-05-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Following CHMP request with assessment of FU2 8.1 the MAH proposed an update of SPC section 4.5 with results from study EGF109275 (effect of long-acting acid-lowering agents on lapatinib absorption)."}, {"id":"IB/0015/G","type":"IB","opinion":"2011-02-04","decision":"2011-02-04","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Type of container - Sterile medicinal products and biological/immunological medicinal products"}, {"id":"IG/0034/G","type":"IG","opinion":"2011-01-06","decision":null,"affects":["Annex II"],"codes":["C.I.9.b","C.I.9.c","C.I.9.e","C.I.9.g","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the contact details of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Changes in the major contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations and described in the DD; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the site undertaking pharmacovigilance activities."}, {"id":"II/0013","type":"II","opinion":"2010-06-24","decision":"2010-07-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Following CHMP request (FUM30) the MAH proposed an update of SPC section 4.8 with information relating to acute renal failure arising from dehydration due to severe diarrhoea. The package leaflet has been updated accordingly. In addition, information on cardiac function has been revised in PL section 4 to be better aligned with SPC section 4.8 as recommended and a correction has been performed to PL section 6."}, {"id":"II/0012","type":"II","opinion":"2010-05-20","decision":"2010-06-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of SPC section 4.5 to include information regarding digoxin interaction further to results of a clinical study. In addition, the MAH proposed to add information regarding interaction with docetaxel as well as to strengthen the existing text regarding the interaction information on paclitaxel in SPC section 4.5. The package leaflet has been updated accordingly."}, {"id":"II/0004","type":"II","opinion":"2010-02-18","decision":"2010-05-05","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.8","5.1","6.5"],"scope":"Extension of indication of Tyverb in combination with an aromatase inhibitor for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer whose tumour overexpress HER-2 not currently intended for chemotherapy. The patients in the pivotal study were not previously treated with trastuzumab or an aromatase inhibitor. SPC sections 4.1, 4.2, 4.3, 4.4, 4.8 and 5.1 have been amended accordingly. Minor editorial changes were also made to the SPC. Consequently, the MAH applied also for an additional pack-size of 84 tablets reflecting the proposed daily dose for this indication. SPC section 6.5, labelling and section 6 of the PL have been updated in this respect."}, {"id":"R/0010","type":"R","opinion":"2010-01-21","decision":"2010-04-29","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0011","type":"II","opinion":"2010-01-21","decision":"2010-04-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.9"],"scope":"Update of SPC sections 4.4 and 4.5 regarding information on interaction with midazolam as well as update of SPC section 4.5 regarding the interaction between lapatinib and irinotecan upon CHMP request. The PL is updated accordingly. Furthermore, SPC section 4.9 has been revised to provide up to date information regarding overdose following CHMP assessment of the last PSUR."}, {"id":"II/0009","type":"II","opinion":"2009-12-17","decision":"2010-01-20","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS) including change of the Qualified Person for Pharmacovigilance (QPPV). Consequently, Annex II has been updated with the new version number."}, {"id":"II/0005","type":"II","opinion":"2009-09-24","decision":"2009-11-05","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of SPC section 4.8 with the Adverse Drug Reactionss \"hypersensitivity reactions including anaphylaxis\" with the frequency rare and \"nail disorders including paronychia\" with the frequency common. The PL has been updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the PL."}, {"id":"II/0003","type":"II","opinion":"2009-01-22","decision":"2009-02-26","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Detailed Description of the Pharmacovigilance System"}, {"id":"II/0001","type":"II","opinion":"2009-01-22","decision":"2009-02-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 to include 2-year carcinogenicity study results. In addition, the MAH took the opportunity to include the Marketing Authorisation numbers and the date of authorization in the respective sections of the SPC and labelling as well as to update the list of local representatives in the package leaflet."} ] }, "larotrectinib__vitrakvi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vitrakvi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/vitrakvi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000361659","type":"IB","opinion":"2026-07-31","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol)"}, {"id":"EMA/R/0000335017","type":"R","opinion":"2026-05-21","decision":"2026-07-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation"}, {"id":"EMA/VR/0000286907","type":"IB","opinion":"2025-08-04","decision":"2026-03-09","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"EMA/VR/0000277850","type":"II","opinion":"2026-01-29","decision":"2026-03-09","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"To update sections 4.2 and 5.2 of the SmPC to reduce the recommended starting dose for paediatric patients from birth to less than 3 months following the assessment of an updated population PK analysis based on the outcome of the Article 46 procedure (EMEA/H/C/004919 P46/009)."}, {"id":"N/0038","type":"N","opinion":"2024-08-14","decision":"2025-07-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"EMA/R/0000257511","type":"R","opinion":"2025-05-22","decision":"2025-07-18","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of conditional marketing authorisation"}, {"id":"R/0035","type":"R","opinion":"2024-05-30","decision":"2024-07-22","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0030","type":"II","opinion":"2023-07-20","decision":"2023-08-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.5, 4.8, and 5.1 of the SmPC in order to update the efficacy data and the list of adverse drug reactions (ADRs) based on interim results from studies 20289 and 20290. In addition, the MAH revised the posology recommendations in patients with liver function abnormalities and amended an existing warning on hepatotoxicity, updated information on drug-drug interaction regarding the effects of CYP3A inhibitors and inducers and P-gp inducers. The Package Leaflet is updated accordingly."}, {"id":"R/0031","type":"R","opinion":"2023-05-25","decision":"2023-07-07","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0027/G","type":"IB","opinion":"2022-09-20","decision":"2023-07-07","affects":["SmPC","PL"],"codes":["B.II.e.1.z","B.II.a.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Other variation; Changes in the composition (excipients) of the finished product - Other variation"}, {"id":"II/0021","type":"II","opinion":"2022-06-10","decision":"2022-08-25","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.2"],"scope":"Update of section 5.2 of the SmPC in order to reflect the outcome of an updated analysis of the population pharmacokinetic (PopPk) model based on additional PK sampling in patients aged 1 month to 6 years from study LOXO-TRK-15003 (SCOUT) imposed as a specific obligation (SOB). The MAH is also proposing to delete this SOB from Annex II. The MAH took the opportunity of this variation to introduce corrections to section 4.8 of the SmPC and to Annex II. In addition the MAH corrected the name of a local representative in the PL."}, {"id":"II/0017","type":"II","opinion":"2021-11-11","decision":"2022-08-25","affects":["SmPC","PL"],"codes":["B.II.d.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Change outside the approved specifications limits range"}, {"id":"IB/0022/G","type":"IB","opinion":"2022-02-08","decision":"2022-08-25","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"R/0014","type":"R","opinion":"2021-06-24","decision":"2021-08-18","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0010/G","type":"II","opinion":"2021-01-28","decision":"2021-08-18","affects":["SmPC","Labelling","PL"],"codes":["A.7","B.II.a.3.b.2","B.II.b.2.a","B.II.b.3.b","B.II.d.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Changes in the composition (excipients) of the finished product - Other excipients - Qualitative or quantitative changes in one or more excipients that may have a significant impact on the safety, quality or efficacy of the product; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change in the manufacturing process of the finished or intermediate product - Substantial changes to a manufacturing process that may have a significant impact on the quality, safety and efficacy of the medicinal product."}, {"id":"IB/0015/G","type":"IB","opinion":"2021-04-16","decision":"2021-08-18","affects":["SmPC","Annex II"],"codes":["A.6","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0008","type":"IAIN","opinion":"2020-08-21","decision":"2021-08-18","affects":["SmPC","PL"],"codes":["B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"R/0006","type":"R","opinion":"2020-06-25","decision":"2020-08-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0001","type":"II","opinion":"2020-06-25","decision":"2020-08-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to reflect the results of study PH-40955 investigating the inductive potential of Larotrectinib on the expression of cytochrome P450 (CYP) enzymes showing that larotrectinib is a weak inducer of PXR regulated enzymes."} ] }, "lazertinib__lazcluze": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lazcluze-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000357738","type":"II","opinion":"2026-09-10","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Can be administered after dispersion in non-carbonated water; and ii) if required, Lazcluze tablet(s) (80 mg or 240 mg) can be administered through a nasogastric tube 8 French or greater. The PL have been updated accordingly."}, {"id":"EMA/VR/0000315717","type":"II","opinion":"2026-02-12","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add information regarding elevations in alkaline phosphatase and bilirubin with lazertinib monotherapy within the ‘hepatotoxicity’ subsection, based on a cumulative safety review. The RMP version 2.1 has also been agreed."}, {"id":"EMA/VR/0000261993","type":"II","opinion":"2025-09-18","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC for Rybrevant and Lazcluze in order to include updated information on enhanced dermatologic management regimen as prophylactic treatment to reduce the risk of dermatological toxicities during treatment, based on results from study 61186372NSC2007. Study 61186372NSC2007 (COCOON) is a Phase 2, open-label, randomized trial evaluating the impact of enhanced versus standard dermatologic management on selected dermatologic adverse events among patients with locally advanced or metastatic EGFR-mutated NSCLC treated first-line with amivantamab + lazertinib. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000253354","type":"II","opinion":"2025-06-19","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to provide final Overall Survival (OS) data following Rybrevant extension of indication procedure (EMEA/H/C/005454/II/0013), and Lazcluze MAA approval (EMEA/H/C/006074/0000), and based on final results from study 73841937NSC3003 (MARIPOSA); this is a pivotal randomized, open-label, Phase 3 study that compares the efficacy and safety of the combination of amivantamab and lazertinib (Arm A) versus osimertinib monotherapy (Arm B) and lazertinib monotherapy (Arm C) in participants with EGFRm NSCLC."} ] }, "lenalidomide__revlimid": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/revlimid-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"II/0130","type":"II","opinion":"2025-06-05","decision":null,"affects":["Annex II"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study CC-5013-MCL-005 listed as a category 3 study in the RMP. This is a non-interventional, post-authorization safety study of patients with relapsed or refractory mantle cell lymphoma to further investigate and characterize the association of lenalidomide with tumor flare reaction and high tumor burden. The RMP version 42.2 was agreed."}, {"id":"SW/0131","type":"SW","opinion":"2025-01-30","decision":"2025-03-28","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Post Authorisation Safety Study results - EMEA/H/C/PSR/S/0049 – Variation"}, {"id":"II/0126","type":"II","opinion":"2023-09-28","decision":"2024-10-09","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Submission of the final report from study CC-5013-MDS-010 listed as an obligation in the Annex II of the Product Information. This is a prospective non-interventional post-authorisation safety study (PASS), designed as a disease registry of patients with transfusion dependent IPSS low or intermediate-1-risk myelodysplastic syndromes (MDS) and isolated del(5q). Section 4.8 of the SmPC is updated with the adverse drug reaction of anaemia in patients with myelodysplastic syndromes. Section D of the Annex II and the RMP (version 39.1) are updated accordingly."}, {"id":"IB/0129/G","type":"IB","opinion":"2024-01-04","decision":"2024-10-09","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0124","type":"II","opinion":"2023-02-09","decision":"2023-07-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update 5-year Overall Survival data following the assessment of procedure II/107 based on study CC-5013-NHL-007, A Phase 3, Double-Blind Randomized Study To Compare The Efficacy And Safety Of Rituximab Plus Lenalidomide (Cc-5013) Versus Rituximab Plus Placebo In Subjects With Relapsed/Refractory Indolent Lymphoma."}, {"id":"II/0123","type":"II","opinion":"2023-06-08","decision":"2023-07-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimisation measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)- approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted."}, {"id":"II/0122","type":"II","opinion":"2022-09-15","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Section 4.2 • Patients with renal impairment The table for Follicular lymphoma patients is updated to also reflect dose adjustment for those with severe renal impairment and end of stage renal disease Follicular lymphoma Renal function (CLcr) Dose adjustment (days 1 to 21 of repeated 28 day cycles)"}, {"id":"IB/0120","type":"IB","opinion":"2021-12-21","decision":"2022-10-14","affects":["Annex II"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"IAIN/0121","type":"IAIN","opinion":"2021-12-09","decision":"2022-10-14","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0116","type":"T","opinion":"2020-10-30","decision":"2020-11-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00001838/201912","type":"PSUSA","opinion":"2020-07-23","decision":"2020-09-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lenalidomide"}, {"id":"II/0112/G","type":"II","opinion":"2020-04-30","decision":"2020-06-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.z","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","6.6"],"scope":"Group of variations including one type II to update sections 4.2, 4.4 and 4.8 of the SmPC and section 4 of the PL with anaphylactic reactions reported with a rare frequency following a safety review and a Type IB variation to update section 6.6 of the SmPC in order to include recommendations to minimise the risk of unintended occupational exposures in healthcare professionals. Section 4.4 of the SmPC and Annex IID have been updated regarding the educational materials, prescribing and dispensing restrictions in order to provide more clarity about the recommended maximum duration of treatment. Finally the MAH took the opportunity to make editorial changes throughout the product information."}, {"id":"II/0107","type":"II","opinion":"2019-11-14","decision":"2019-12-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include Revlimid in combination with rituximab (anti-CD20 antibody) for the treatment of adult patients with previously treated follicular lymphoma (Grade 1 – 3a); as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated; the PL is updated in accordance. The RMP version 37.0 has also been agreed."}, {"id":"II/0102/G","type":"II","opinion":"2019-03-28","decision":"2019-05-13","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.5"],"scope":"Extension of indication to include treatment with Revlimid in combination with bortezomib and dexamethasone of adult patients with previously untreated multiple myeloma who are not eligible for transplant. As a consequence, the MAH submitted a request to add 7-capsule pack sizes for the 7.5 mg, 20 mg and 25 mg strengths of Revlimid (lenalidomide) to support the proposed posology and lenalidomide dose modification. Sections 4.1, 4.2, 4.4, 4.8, 5.1, 6.5 and 8 of the SmPC are updated; the Package Leaflet is updated in accordance."}, {"id":"IB/0103","type":"IB","opinion":"2018-11-13","decision":"2019-05-13","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0106","type":"IAIN","opinion":"2019-02-11","decision":"2019-05-13","affects":["Annex II"],"codes":["C.I.11.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of wording agreed by the competent authority"}, {"id":"IAIN/0104/G","type":"IAIN","opinion":"2018-11-19","decision":"2019-05-13","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.c.1","B.II.e.6.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that does not affect the product information"}, {"id":"IA/0109","type":"IA","opinion":"2019-03-13","decision":"2019-05-13","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"T/0101","type":"T","opinion":"2018-06-15","decision":"2018-06-29","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0098","type":"II","opinion":"2018-05-17","decision":"2018-06-29","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC and of the Annex II key elements of the risk minimisation programme with information on prescription duration and to revise due dates of the PASS CC-5013-MDS-10 and 12; furthermore, the RMP version 35.1 has been revised in line with the updated Guideline on Good Pharmacovigilance Practices (GVP) Module V to propose the reclassification and/or renaming of known safety concerns associated with the use of lenalidomide. Consequently, Annex IID has been updated accordingly also to remove activities deemed not to belong to the risk minimisation measures."}, {"id":"II/0097","type":"II","opinion":"2018-04-19","decision":"2018-06-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the SmPC section 4.8 to include solid organ transplant rejection as an adverse reaction (ADR) with the frequency not known in line with the Company Core Data Sheet (CCDS). The MAH also took the opportunity to further align the SmPC section 4.8 with the CCDS by adding the following ADRs reported as serious in some clinical trials: cellulitis, hypercalcaemia, and musculoskeletal and connective tissue pain and discomfort (including back pain). Minor editorial changes have been introduced throughout the PI. The Package leaflet has been updated accordingly."}, {"id":"PSUSA/00001838/201612","type":"PSUSA","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lenalidomide"}, {"id":"IB/0092/G","type":"IB","opinion":"2017-01-31","decision":"2017-09-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0089/G","type":"II","opinion":"2017-01-26","decision":"2017-02-23","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to add maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation; as a consequence, SmPC sections 4.1, 4.2, 4.4, 4.8 and 5.1 have been updated and the Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC and Package Leaflet. A revised version of the RMP (version 34.0) has been approved as part of this application. Furthermore, the MAH introduced 7-day pack sizes for the 10 mg and 15 mg strengths with subsequent changes to the Product Information."}, {"id":"R/0091","type":"R","opinion":"2016-12-15","decision":"2017-02-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0090","type":"IB","opinion":"2016-10-26","decision":"2017-02-16","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"PSUSA/1838/ Periodic Safety Update EU Single assessment - 21/07/2016 09/09/2016 SmPC Refer to Scientific conclusions and grounds recommending 201512 lenalidomide the variation to terms of the Marketing Authorisation(s)’ for PSUSA/1838/201512."}, {"id":"IB/0088","type":"IB","opinion":"2016-07-14","decision":"2016-09-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0079","type":"II","opinion":"2016-01-28","decision":"2016-07-08","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.7","4.8","5.1","5.2"],"scope":"Extension of Indication to add treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL); as a consequence, SmPC sections 4.1, 4.2, 4.4, 4.7, 4.8, 5.1 and 5.2 have been updated and the Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC and Package Leaflet. A revised version of the RMP (version 29.0) has been approved as part of this application."}, {"id":"II/0082","type":"II","opinion":"2015-06-11","decision":"2016-06-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IAIN/0081","type":"IAIN","opinion":"2015-04-16","decision":"2016-06-01","affects":["SmPC","PL"],"codes":["C.I.12"],"outcome":"accepted","kind":"other","sections":[],"scope":"Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring"}, {"id":"X/0073/G","type":"X","opinion":"2014-12-18","decision":"2015-02-19","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0072","type":"II","opinion":"2014-02-20","decision":"2014-09-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.6","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add hyperthyroidism and leukocytoclastic vasculitis as adverse drug reactions (ADRs) further to a PRAC request made during the assessment of Revlimid PSUR 08. The MAH took this opportunity to include minor changes to sections 4.4, 4.5, 4.6, 4.8 and 5.1 of the SmPC based on previously approved wordings. The Package Leaflet is updated accordingly."}, {"id":"II/0070","type":"II","opinion":"2014-07-24","decision":"2014-09-30","affects":["SmPC","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUV/0069","type":"PSUV","opinion":"2013-09-19","decision":"2013-11-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0056","type":"II","opinion":"2013-04-25","decision":"2013-06-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication to include patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate for Revlimid."}, {"id":"IB/0061/G","type":"IB","opinion":"2013-04-19","decision":"2013-06-13","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"II/0060","type":"II","opinion":"2012-12-13","decision":"2013-01-17","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to propose 7.5 mg daily dosing as an alternative to 15 mg dosing every other day for patients with severe renal impairment (creatinine clearance [CLcr] < 30 mL/min, not requiring dialysis). Furthermore, the PI is being brought in line with the latest QRD template version 8 rev.2 for the update of the Annex II."}, {"id":"II/0058","type":"II","opinion":"2012-10-18","decision":"2012-11-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC regarding lenalidomide-induced hepatotoxicity further to the request of the CHMP (PSUR 7 and FU2 006.1). The Package Leaflet has been udpated accordingly. Section 4.5 of the SmPC was also updated to include a caution with potent P-gp inhibitors, whereby their concomitant use should be avoided due to increased plasma levels and toxicity."}, {"id":"X/0046/G","type":"X","opinion":"2012-06-21","decision":"2012-09-10","affects":[],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"R/0054","type":"R","opinion":"2012-02-16","decision":"2012-04-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"A20/0048","type":"A20","opinion":"2011-09-22","decision":"2012-01-13","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Pursuant to Article 20 of Regulation (EC) No 726/2004, the European Commission requested on 09 March 2011 the opinion of the CHMP on measures necessary to ensure the safe and effective use of the above mentioned medicinal product further to an increased incidence of second primary malignancies observed in newly diagnosed multiple myeloma patients, and to review its impact on the benefit risk balance of the currently approved indication."}, {"id":"IA/0051/G","type":"IA","opinion":"2011-07-04","decision":null,"affects":["Annex II","PL"],"codes":["B.I.a.1.f","B.II.b.2.a","B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place; Change to batch release arrangements and quality control testing of the FP - Replacement or addition of a site where batch control/testing takes place; Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"IA/0049","type":"IA","opinion":"2011-05-16","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0042/G","type":"II","opinion":"2010-12-16","decision":"2011-01-21","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the Summary of Product Characteristics regarding the absorption of lenalidomide in both the fed and fasted state based on data from Phase I studies in healthy volunteers and a Phase II study in patients with multiple myeloma. Changes were also made regarding the metabolism and excretion of lenalidomide in both healthy volunteers and in patients with multiple myeloma. As a consequence, redundant text was deleted and minor corrections were also made. The Marketing Authorisation Holder also took the opportunity to update Annex II to delete the version number of the DDPS."}, {"id":"II/0041","type":"II","opinion":"2010-10-21","decision":"2010-12-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","4.9"],"scope":"Update of section 4.2 of the Summary of Product Characteristics (SmPC) and the Package Leaflet to clarify that Revlimid capsules should not be opened and that dose management in patients with renal impairment should be based upon individual patient treatment tolerance as well as update of section 4.9 of the SmPC with additional information relating to available experience with overdose with lenalidomide."}, {"id":"II/0034","type":"II","opinion":"2010-10-21","decision":"2010-12-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the Summary of Product Characteristics (SmPC) to bring it in line with the Company Core Data Sheet and the SmPC guideline. The Package leaflet has been updated accordingly."}, {"id":"II/0032","type":"II","opinion":"2010-09-23","decision":"2010-12-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the Summary of Product Characteristics with respect to arterial thromboembolic events and risk of thromboembolic events, following the request of the CHMP in the assessment of PSUR 5. Annex II, Annex 127a and the package leaflet have been updated accordingly. The MAH has taken the opportunity to also update the Product Information to the latest QRD template, version 7.3.1, along with minor formatting corrections."}, {"id":"II/0033","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC, with respect to data from ECOG E4A03 study, further to the request of the CHMP (FU2 022.2). The package leaflet has been updated accordingly."}, {"id":"IA/0043","type":"IA","opinion":"2010-10-13","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"IA/0037/G","type":"IA","opinion":"2010-07-06","decision":null,"affects":["Annex II"],"codes":["C.I.9.a","C.I.9.c","C.I.9.e","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Changes in the major contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations and described in the DD; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"II/0027","type":"II","opinion":"2010-02-18","decision":"2010-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the Summary of Product Characteristics (SmPC) to add a warning on myocardial infarction and to add it as a common adverse reaction in section 4.8 of the SmPC and in the package leaflet, further to the request of the CHMP in the assessment of the 4th Periodic Safety Update Report."}, {"id":"IB/0031","type":"IB","opinion":"2010-03-22","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Implementation of change(s) requested following the assessment of an USR, class labelling, a PSUR, RMP, FUM/SO, data submitted under A 45/46, or amendments to reflect a Core SPC - Changes with NO new additional data are submitted by the MAH"}, {"id":"II/0028","type":"II","opinion":"2009-11-19","decision":"2010-01-12","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Summary of Product Characteristics (SPC) with the updated pooled follow-up analysis from Study CC-5013-MM-009 and Study CC-5013-MM-010, further to the request of the CHMP (FUM 020). Annex II was also updated in line with the latest QRD template (version 7.3) and the MAH also took the opportunity to update the version number of the Risk Management Plan with the latest agreed version 10.0."}, {"id":"II/0029","type":"II","opinion":"2009-10-22","decision":"2010-01-08","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the Summary of Product Characteristics (SPC) with the final results from the pilot embryo-foetal development Study CC-5013-TOX-004, at the request of the CHMP (FUM 014). Annex II & IV have been updated accordingly to reflect that the results are now final."}, {"id":"IB/0030","type":"IB","opinion":"2009-12-17","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"To change the storage conditions of the finished product"}, {"id":"II/0026","type":"II","opinion":"2009-09-24","decision":"2009-12-16","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","5.2"],"scope":"Update of sections 4.4, 4.6 and 5.2 of the SPC further to the results of study CC-5013-PK-008, conducted as a post-authorisation commitment to evaluate the transfer of lenalidomide in semen in healthy volunteers which confirmed the presence of lenalidomide in human semen (FU2 025.1). Annex II, the Package Leaflet and Annex IV have been updated accordingly."}, {"id":"II/0024","type":"II","opinion":"2009-09-24","decision":"2009-10-19","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS) to version 6.0, in light of a reorganisation within Celgene's Drug Safety Department concerning the risk management activities. Consequently, Annex II has been updated with the new version number of the agreed DDPS."}, {"id":"II/0025","type":"II","opinion":"2009-06-25","decision":"2009-08-07","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Further to the request of the CHMP during the assessment of the 3rd PSUR, the Marketing Authorisation Holder (MAH) applied to update section 4.4 of the Summary of Product Characteristics (SPC) to add warnings on allergic reactions (including hypersensitivity reactions and cross-allergy with thalidomide) and on severe skin reactions, and to update the warning concerning the use of erythropoietic agents with the currently approved threshold of Hb target (i.e 12 g/dl), and section 4.8 to add hypersensitvity reactions and Tumour Lysis Syndrome as rare adverse reactions. The Package Leaflet has been updated accordingly."}, {"id":"II/0014","type":"II","opinion":"2009-01-22","decision":"2009-02-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SPC to add the adverse events Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Angioedema reported during the post-marketing period, and of section 4.4 and 4.8 of the SPC in order to include haemorrhagic potential related to concomitant antithrombotic treatment and haemorragic adverse reactions, further to the request from the CHMP following the assessment of the 2nd PSUR. The Package Leaflet is updated accordingly."}, {"id":"IB/0020","type":"IB","opinion":"2009-01-23","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0017","type":"II","opinion":"2008-11-20","decision":"2008-12-22","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"The scope of this variation is to update the section 4.2 of the SPC in line with the outcome of FUM 019 (dose schedule in renal impairment). In this same section 4.2, for the sake of clarity, the MAH also proposes to amend the table that describes the dose adjustment for patients who are affected by neutropenia during treatment."}, {"id":"II/0015","type":"II","opinion":"2008-10-23","decision":"2008-11-20","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS). Consequently, Annex II of the product information has been updated to include the latest version number (version 5.1) of the DDPS agreed by the CHMP."}, {"id":"II/0016","type":"II","opinion":"2008-09-25","decision":"2008-10-27","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of the information on the interaction with oral contraceptives in section 4.5 further to the request of the CHMP following the assessment of the results of in vitro evaluation of Revlimid as an inducer of cytochrome P450 expression in cultured hepatocytes (FUM 018). The study indicates that lenalidomide up to 10 ?M CC-5013, twice daily for three consecutive days does not induce CYP1A2, 2B6, 2C9, 2C19 and CYP3A4/5 in cultured human hepatocytes."}, {"id":"II/0005","type":"II","opinion":"2008-06-26","decision":"2008-08-22","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS). Consequently, Annex II of the product information has been updated to include the latest version number (version 5.1) of the DDPS agreed by the CHMP."}, {"id":"IA/0013","type":"IA","opinion":"2008-08-07","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"II/0008","type":"II","opinion":"2008-05-30","decision":"2008-07-31","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","5.3"],"scope":"Update of sections 4.4, 4.6 and 5.3 of the SPC with regard to non-clinical safety findings of teratogenicity in monkeys, upon request from the CHMP. A new version of the EU RMP is also proposed to reflect these findings. Annex II, Labelling, Package Leaflet and Annex IV have been updated accordingly."}, {"id":"II/0002","type":"II","opinion":"2008-01-24","decision":"2008-03-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.6"],"scope":"This type II variation concerns an update of section 4.4 of the SPC with a clarification on the interval between prescription and dispensing and a warning on potential Tumour Lysis Syndrome and sections 4.4 and 4.6 of the SPC with clarifications regarding pregnancy testing and information concerning female partners of male patients who become pregnant. The Package Leaflet has been updated accordingly. Further, the Marketing Authorisation Holder (MAH) takes the opportunity to implement minor changes to the annexes IIB and IV in line with the latest Risk Management Plan approved by the CHMP (version 6.0) and to make minor editorial changes to the SPC, labelling and Package Leaflet."}, {"id":"IA/0003","type":"IA","opinion":"2007-12-11","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"} ] }, "lenvatinib__kisplyx": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kisplyx-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kisplyx-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000328217","type":"IB","opinion":"2026-03-26","decision":null,"affects":["SmPC"],"codes":["C.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Type IB, to update section 4.8 of the EN SmPC, resulting from the final assessment report, dated 11 December 2025, for paediatric study E7080-G000-231, which was submitted in accordance with Article 46 of regulation (EC) No 1901/2006 (Procedure no.: EMA/PAM/0000279817 and EMA/PAM/0000279841)."}, {"id":"EMA/VR/0000254997","type":"IAIN","opinion":"2025-04-17","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"WS/2631","type":"WS","opinion":"2024-03-21","decision":"2024-05-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC for Kisplyx and sections 4.8, 5.1 and 5.2 of the SmPC for Lenvima, in order to reflect the results of two completed paediatric clinical studies E7080-G000-216 (216) and E7080-G000-231 (231). Study 216 is a Phase 1/2, multicenter, open-label, single arm study of lenvatinib in combination with everolimus in pediatric subjects (and young adults aged ≤21 years) with relapsed or refractory malignant solid tumors. Study 231 is a Phase 2, open-label, multicenter basket study to evaluate the antitumor activity and safety of Lenvatinib in children, adolescents, and young adults with relapsed or refractory solid malignancies."}, {"id":"II/0058","type":"II","opinion":"2024-03-14","decision":"2024-05-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-B61; this is a phase 2, single-arm, open-label clinical trial of pembrolizumab plus lenvatinib in participants with first-line advanced/metastatic non-clear cell Renal Cell Carcinoma (nccRCC). In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0055","type":"II","opinion":"2023-08-31","decision":"2024-05-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information (OS, PFS, ORR and PFS2) in first-line treatment of patients with advanced renal cell carcinoma treated with Kisplyx in combination with pembrolizumab, based on the final analysis for the overall population and by risk prognosis subgroups from study E7080-G000-307/CLEAR; this is a multicenter, randomized, open-label, phase 3 study comparing the efficacy and safety of lenvatinib in combination with either pembrolizumab or everolimus versus sunitinib alone in first-line treatment of subjects with advanced renal cell carcinoma (RCC)."}, {"id":"II/0052","type":"II","opinion":"2023-04-14","decision":"2024-05-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC based on pooled safety data including results of Study 307, an ongoing, multicenter, randomised, open-label study that is being conducted to compare the efficacy and safety of lenvatinib in combination with everolimus or pembrolizumab versus sunitinib as first-line (1L) treatment in adults with advanced renal cell carcinoma (RCC). The provision of the CSR addresses the post-authorisation measure MEA/FSR 009.3. The Package Leaflet is updated accordingly. An updated RMP version 15.0 has been submitted."}, {"id":"IG/1641","type":"IG","opinion":"2023-07-25","decision":"2024-05-06","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2312","type":"WS","opinion":"2023-02-23","decision":"2023-04-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"To update of SmPC sections 4.2 and 6.6 to include the option of administering the capsules as a suspension, including instructions for the administration and preparation of the suspension. The MAH also took the opportunity to include some editorial changes to the SmPC. The package leaflet have been updated accordingly."}, {"id":"WS/2235","type":"WS","opinion":"2022-04-07","decision":"2023-04-17","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC of Lenvima and Kisplyx in order to add colitis to the list of ADRs with frequency uncommon for monotherapy/ combination with everolimus and common for combination with pembrolizumab, following PRAC Signal assessment of colitis with lenvatinib (EPITT no: 19691). The Package Leaflets are updated accordingly."}, {"id":"II/0045","type":"II","opinion":"2021-10-14","decision":"2021-11-26","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include Kisplyx in combination with pembrolizumab first line treatment of adults with advanced renal cell carcinoma (RCC); as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 13 of the RMP has also been submitted. In addition, the Marketing authorisation holder took the opportunity to make editorial changes and update the list of local representatives in the Package Leaflet."}, {"id":"WS/1861/G","type":"WS","opinion":"2020-12-10","decision":"2021-06-17","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC following the submission of the final clinical study report (CSR) for Study E7080-G000-201 (Study 201) - To evaluate the long-term safety of lenvatinib in Medullary and Iodine-131 Refractory, Unresectable differentiated thyroid carcinoma (DTC), Stratified by Histology (MEA 001 for Lenvima; from initial MAA for Kisplyx). Submission of the final CSR for Study E7080-G000-303 (Study 303) - To evaluate long-term safety of lenvatinib in patients with RR-DTC (radioiodine refractory differentiated thyroid cancer) in a randomized, double-blind, placebo-controlled Phase 3 study (MEA 004 for Lenvima; MEA 002 for Kisplyx)."}, {"id":"R/0043","type":"R","opinion":"2021-04-22","decision":"2021-06-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0041","type":"II","opinion":"2021-03-18","decision":"2021-06-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update the drug-drug interaction with everolimus based on data from study 221, a single-arm, multicenter, Phase 2 trial to evaluate the safety and efficacy of lenvatinib in combination with everolimus in subjects with unresectable advanced or metastatic nccRCC who have not received any chemotherapy for advanced disease. (MEA 008.1). The RMP version 12.1 is submitted."}, {"id":"IG/1370","type":"IG","opinion":"2021-03-17","decision":"2021-06-17","affects":["SmPC","Annex II"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IG/1366/G","type":"IG","opinion":"2021-03-04","decision":"2021-06-17","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"PSUSA/00010380/202002","type":"PSUSA","opinion":"2020-09-17","decision":"2020-11-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lenvatinib"}, {"id":"IG/1263","type":"IG","opinion":"2020-06-24","decision":"2020-11-18","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IG/1260/G","type":"IG","opinion":"2020-06-24","decision":"2020-11-18","affects":["SmPC","Labelling","PL"],"codes":["A.1","A.5.a","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"WS/1607","type":"WS","opinion":"2019-06-27","decision":"2020-06-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on the results of Study E7080-A001- 010, a Multicenter Phase 0 Study in Healthy Subjects and Subjects with Either Hepatic or Renal Impairment to Obtain Plasma for Assessment of in Vitro Lenvatinib Protein Binding."}, {"id":"IB/0028/G","type":"IB","opinion":"2019-10-04","decision":"2020-06-25","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IAIN/0029","type":"IAIN","opinion":"2019-09-18","decision":"2020-06-25","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"WS/1444","type":"WS","opinion":"2018-10-25","decision":"2019-02-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of Sections 4.4 and 4.8 of the SmPC to amend the existing warnings on proteinuria and non-gastro-intestianl fistula and to add pneumothorax and nephrotic syndrome as new adverse drug reactions (ADRs) with uncommon frequency. The PL is updated accordingly."}, {"id":"WS/1396","type":"WS","opinion":"2018-09-13","decision":"2019-02-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to include that there is no significant drug-drug interaction risk with midazolam, based on the results of study E7080-A001-109 (A Phase 1 Study to determine DDI of lenvatinib and midazolam, a cytochrome P450 3A4 (CYP3A4) substrate, in subjects with advanced solid tumors). The RMP is updated (version 10.4)"}, {"id":"WS/1363","type":"WS","opinion":"2018-06-21","decision":"2019-02-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Serious complications of poorly controlled hypertension, including aortic dissection, have been reported with the use of lenvatinib. No formal studies of the effect of lenvatinib on wound healing have been conducted. Impaired wound healing has been reported in patients receiving lenvatinib. Temporary interruption of lenvatinib should be considered in patients undergoing major surgical procedures. There is limited clinical experience regarding the timing of reinitiation of lenvatinib following a major surgical procedure. Therefore, the decision to resume lenvatinib following a major surgical procedure should be based on clinical judgment of adequate wound healing."}, {"id":"T/0022","type":"T","opinion":"2019-01-17","decision":"2019-02-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IG/1045","type":"IG","opinion":"2019-01-11","decision":"2019-02-07","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/1161","type":"WS","opinion":"2017-06-01","decision":"2018-03-07","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"WS/1123","type":"WS","opinion":"2017-03-23","decision":"2018-03-07","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.2"],"scope":"Update of section 4.8 of the SmPC to add the adverse events “cholecystitis” with frequency common, and the adverse events “pancreatitis”, “amylase Increased” and “lipase increased” with frequencies uncommon, common and common, respectively. The Package Leaflet is updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to implement a correction to section 5.2 of the SmPC for both products and to combine the Kisplyx SmPC."}, {"id":"N/0008","type":"N","opinion":"2017-11-22","decision":"2018-03-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0001","type":"II","opinion":"2017-01-26","decision":"2017-02-27","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to add a warning on \"haemorrhage\" and posology recommendations and a warning on \"non-gastrointestinal fistula\" in line with what was approved for Lenvima. The package leaflet is updated accordingly. In addition, the format of the EU authorisation numbers is corrected throughout the product information."} ] }, "lenvatinib__lenvima": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lenvima-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lenvima-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000328217","type":"IB","opinion":"2026-03-26","decision":null,"affects":["SmPC"],"codes":["C.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Type IB, to update section 4.8 of the EN SmPC, resulting from the final assessment report, dated 11 December 2025, for paediatric study E7080-G000-231, which was submitted in accordance with Article 46 of regulation (EC) No 1901/2006 (Procedure no.: EMA/PAM/0000279817 and EMA/PAM/0000279841)."}, {"id":"EMA/VR/0000254997","type":"IAIN","opinion":"2025-04-17","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"IB/0057","type":"IB","opinion":"2024-10-18","decision":null,"affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update SmPC section 4.8 and 5.1 to add the final data from Study 230 following assessment in two P46 procedures. The PIP compliance with EMEA-001119-PIP02-12-M08 has been confirmed."}, {"id":"WS/2631","type":"WS","opinion":"2024-03-21","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC for Kisplyx and sections 4.8, 5.1 and 5.2 of the SmPC for Lenvima, in order to reflect the results of two completed paediatric clinical studies E7080-G000-216 (216) and E7080-G000-231 (231). Study 216 is a Phase 1/2, multicenter, open-label, single arm study of lenvatinib in combination with everolimus in pediatric subjects (and young adults aged ≤21 years) with relapsed or refractory malignant solid tumors. Study 231 is a Phase 2, open-label, multicenter basket study to evaluate the antitumor activity and safety of Lenvatinib in children, adolescents, and young adults with relapsed or refractory solid malignancies."}, {"id":"II/0053","type":"II","opinion":"2023-11-30","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Submission of interim results from study E7080-M000-508 (STELLAR), listed as a category 3 PASS in the RMP. This is a non-interventional multicentre, observational, phase 4 study to evaluate the safety and tolerability of lenvatinib in patients with advanced or unresectable HCC. Update of section 4.8 of the SmPC to include ‘gastrointestinal perforation’ as an adverse drug reaction with frequency ‘common’. The package leaflet has been updated accordingly. RMP version 15.2 has also been submitted."}, {"id":"II/0050","type":"II","opinion":"2023-11-09","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to update paediatric information based on final results from studies E7080-G000-207 and E7080-G000-230. Study E7080-G000-207 is a multicenter, open-label, Phase 1/2 study of lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma; Study E7080-G000-230 is a multicenter, open-label, randomized Phase 2 study to compare the efficacy and safety of lenvatinib in combination with ifosfamide and etoposide versus ifosfamide and etoposide in children, adolescents and young adults with Relapsed or Refractory Osteosarcoma (OLIE). The Package Leaflet is updated accordingly."}, {"id":"IG/1641","type":"IG","opinion":"2023-07-25","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2312","type":"WS","opinion":"2023-02-23","decision":"2023-05-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"To update of SmPC sections 4.2 and 6.6 to include the option of administering the capsules as a suspension, including instructions for the administration and preparation of the suspension. The MAH also took the opportunity to include some editorial changes to the SmPC. The package leaflet have been updated accordingly."}, {"id":"WS/2235","type":"WS","opinion":"2022-04-07","decision":"2023-05-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC of Lenvima and Kisplyx in order to add colitis to the list of ADRs with frequency uncommon for monotherapy/ combination with everolimus and common for combination with pembrolizumab, following PRAC Signal assessment of colitis with lenvatinib (EPITT no: 19691). The Package Leaflets are updated accordingly."}, {"id":"II/0049","type":"II","opinion":"2023-03-09","decision":"2023-05-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the efficacy information of \"Endometrial carcinoma\" based on the final OS analysis data for the overall population as well as for MMR subgroups from study E7080-G000-309 / KEYNOTE-775. This is a Multicenter, Open-label, Randomized, Phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician’s choice in participants with advanced endometrial cancer. In addition, the MAH took the opportunity to implement editorial changes in the SmPC."}, {"id":"WS/1861/G","type":"WS","opinion":"2020-12-10","decision":"2021-11-26","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC following the submission of the final clinical study report (CSR) for Study E7080-G000-201 (Study 201) - To evaluate the long-term safety of lenvatinib in Medullary and Iodine-131 Refractory, Unresectable differentiated thyroid carcinoma (DTC), Stratified by Histology (MEA 001 for Lenvima; from initial MAA for Kisplyx). Submission of the final CSR for Study E7080-G000-303 (Study 303) - To evaluate long-term safety of lenvatinib in patients with RR-DTC (radioiodine refractory differentiated thyroid cancer) in a randomized, double-blind, placebo-controlled Phase 3 study (MEA 004 for Lenvima; MEA 002 for Kisplyx)."}, {"id":"II/0042","type":"II","opinion":"2021-10-14","decision":"2021-11-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include lenvatinib in combination with pembrolizumab for the treatment of adult patients with advanced endometrial carcinoma (EC) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 14.1 of the RMP has also been agreed. In addition, the MAH took the opportunity to make minor editorial changes to the SmPC, Annex II and to update the list of local representatives in the Package Leaflet in line with the latest QRD template version 10.2."}, {"id":"IG/1370","type":"IG","opinion":"2021-03-17","decision":"2021-11-26","affects":["SmPC","Annex II"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IG/1366/G","type":"IG","opinion":"2021-03-04","decision":"2021-11-26","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"PSUSA/00010380/202002","type":"PSUSA","opinion":"2020-09-17","decision":"2020-11-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lenvatinib"}, {"id":"IG/1263","type":"IG","opinion":"2020-06-24","decision":"2020-11-18","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IG/1260/G","type":"IG","opinion":"2020-06-24","decision":"2020-11-18","affects":["SmPC","Labelling","PL"],"codes":["A.1","A.5.a","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"WS/1607","type":"WS","opinion":"2019-06-27","decision":"2020-05-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on the results of Study E7080-A001- 010, a Multicenter Phase 0 Study in Healthy Subjects and Subjects with Either Hepatic or Renal Impairment to Obtain Plasma for Assessment of in Vitro Lenvatinib Protein Binding."}, {"id":"R/0031","type":"R","opinion":"2020-03-26","decision":"2020-05-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0030/G","type":"IB","opinion":"2019-10-04","decision":"2020-05-20","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IAIN/0029","type":"IAIN","opinion":"2019-09-18","decision":"2020-05-20","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"WS/1444","type":"WS","opinion":"2018-10-25","decision":"2019-02-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of Sections 4.4 and 4.8 of the SmPC to amend the existing warnings on proteinuria and non-gastro-intestianl fistula and to add pneumothorax and nephrotic syndrome as new adverse drug reactions (ADRs) with uncommon frequency. The PL is updated accordingly."}, {"id":"WS/1396","type":"WS","opinion":"2018-09-13","decision":"2019-02-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to include that there is no significant drug-drug interaction risk with midazolam, based on the results of study E7080-A001-109 (A Phase 1 Study to determine DDI of lenvatinib and midazolam, a cytochrome P450 3A4 (CYP3A4) substrate, in subjects with advanced solid tumors). The RMP is updated (version 10.4)"}, {"id":"T/0024","type":"T","opinion":"2019-01-17","decision":"2019-02-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IG/1045","type":"IG","opinion":"2019-01-11","decision":"2019-02-07","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/1363","type":"WS","opinion":"2018-06-21","decision":"2018-08-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Serious complications of poorly controlled hypertension, including aortic dissection, have been reported with the use of lenvatinib. No formal studies of the effect of lenvatinib on wound healing have been conducted. Impaired wound healing has been reported in patients receiving lenvatinib. Temporary interruption of lenvatinib should be considered in patients undergoing major surgical procedures. There is limited clinical experience regarding the timing of reinitiation of lenvatinib following a major surgical procedure. Therefore, the decision to resume lenvatinib following a major surgical procedure should be based on clinical judgment of adequate wound healing."}, {"id":"II/0011/G","type":"II","opinion":"2018-06-28","decision":"2018-08-20","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy; consequently, sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2 of the SmPC are being updated and the package leaflet is updated accordingly. In addition, section 4.2 of the SmPC is being updated to add that the product can be administered as a suspension in water or apple juice. In addition, the labelling is updated to include the unique identifier. The RMP was updated (version 10.6). The Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"WS/1161","type":"WS","opinion":"2017-06-01","decision":"2017-09-21","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"WS/1123","type":"WS","opinion":"2017-03-23","decision":"2017-09-21","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.2"],"scope":"Update of section 4.8 of the SmPC to add the adverse events “cholecystitis” with frequency common, and the adverse events “pancreatitis”, “amylase Increased” and “lipase increased” with frequencies uncommon, common and common, respectively. The Package Leaflet is updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to implement a correction to section 5.2 of the SmPC for both products and to combine the Kisplyx SmPC."}, {"id":"II/0004","type":"II","opinion":"2016-09-15","decision":"2017-09-21","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to amend the already existing information on haemorrhage and fistula formation. The package leaflet is updated accordingly. Minor changes were made throughout the product information and changes were made in line with the product information of Kisplyx. The SmPCs of the 4mg and 10mg strengths were combined in line with the latest QRD template (version 10)."} ] }, "leuprorelin__camcevi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/camcevi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/camcevi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000349380","type":"IB","opinion":"2026-09-15","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["Q.II.f.1.d","C.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the shelf life or storage - Change in storage conditions of the finished product or the diluted/reconstituted product; Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a Union referral procedure - Other variation"}, {"id":"EMA/X/0000258054","type":"X","opinion":"2026-02-26","decision":"2026-04-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to add a new strength of 21 mg for Leuproelin prolonged-release suspension for injection pre-filled syringe, for subcutaneous (SC) administration."}, {"id":"EMA/VR/0000261705","type":"IAIN","opinion":"2025-04-03","decision":"2025-06-27","affects":["Annex II","PL"],"codes":["B.II.b.2.a","B.II.b.2.c.2","B.II.b.1.a","A.5.b","A.4","B.I.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the finished product - Replacement or addition of a site where batch control/testing takes place; Replacement or addition of a manufacturer responsible for importation and/or batch release - Including batch control/testing; Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Secondary packaging site; Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release."}, {"id":"IB/0006/G","type":"IB","opinion":"2024-07-05","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.b.5.z","B.IV.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to in-process tests or limits applied during the manufacture of the finished product - Other variation; Change of a measuring or administration device - Other variation"}, {"id":"N/0008","type":"N","opinion":"2024-06-19","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00010877/202307","type":"PSUSA","opinion":"2024-03-21","decision":"2024-05-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - leuprorelin (depot formulations)"}, {"id":"IB/0001","type":"IB","opinion":"2023-05-11","decision":"2024-05-27","affects":["SmPC","PL"],"codes":["C.I.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the SPC, Labelling or PL of a generic/hybrid/biosimilar products following assessment of the same change for the reference product - Implementation of change(s) for which NO new additional data is required to be submitted by the MAH"} ] }, "linvoseltamab__lynozyfic": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lynozyfic-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000273555","type":"IB","opinion":"2025-07-21","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.5","B.I.d.1.a.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol; Re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data"} ] }, "lisocabtagene-maraleucel__breyanzi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/breyanzi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/breyanzi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000327431","type":"II","opinion":"2026-07-23","decision":null,"affects":["Annex II","Labelling"],"codes":["C.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study CA082-1105 listed as a Specific Obligation in the Annex II of the Product Information. This is a non-interventional study submitted to summarize the consistency of Breyanzi product batch quality data measured at the time of release and clinical outcomes in patients treated with Breyanzi in the post-marketing setting for R/R LBCL within the approved indications and dose range per the EU PI. The Annex II and the RMP version 10.0 are updated accordingly. In addition, the MAH took the opportunity to make a minor editorial update by removing some grey shading from Annex III."}, {"id":"EMA/VR/0000272242","type":"II","opinion":"2025-10-16","decision":"2025-11-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.7","4.8"],"scope":"Update of sections 4.2, 4.4, 4.7 and 4.8 of the SmPC in order to update the post-treatment safety monitoring information based on clinical trials and real-world data. The Package leaflet section and the annex II are updated in accordance. The applicant also took the occasion to update the list of local representatives for Iceland in the package leaflet. Version 9.1 of the RMP has also been submitted. Breyanzi should refrain from driving or operating heavy or potentially dangerous machines for at least 4 weeks after Breyanzi infusion, or longer at the physician’s discretion For more information, please refer to the Summary of Product Characteristics."}, {"id":"EMA/VR/0000265024","type":"II","opinion":"2025-10-16","decision":"2025-11-21","affects":["SmPC","Labelling","PL"],"codes":["B.II.d.1.e","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Change in the specification parameters and/or limits of the finished product - Change outside the approved specifications limits range"}, {"id":"EMA/VR/0000264124","type":"II","opinion":"2025-10-16","decision":"2025-11-21","affects":["SmPC","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"A grouped application consisting of: Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study JCAR017-BCM-003; this is a global randomized multicenter phase 3 trial to compare the efficacy and safety of JCAR017 to standard of care in adult subjects with high-risk, transplant-eligible relapsed or refractory aggressive B-cell Non-Hodgkin lymphomas (TRANSFORM). In addition, final study reports for studies 017006 and JCAR017-BCM-001 Cohort 2 are submitted to support the main scope. remove the dose verification worksheet statement from the Labelling."}, {"id":"II/0043/G","type":"II","opinion":"2025-01-30","decision":"2025-03-12","affects":["SmPC","PL"],"codes":["B.II.d.1.e","B.II.d.1.a","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for Breyanzi to include treatment of adult patients with 3rd line + follicular lymphoma (FL) based on final results from the pivotal study JCAR017-FOL-001 (FOL-001, TRANSCEND-FL). This is a phase 2, open-label, single-arm, multicohort, multicenter study to evaluate efficacy and safety of JCAR017 in adult subjects with relapsed or refractory (r/r) follicular Lymphoma (FL) or marginal zone lymphoma (MZL). As a consequence, sections 4.1, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is also updated in accordance. Version 5.1 of the RMP was also submitted."}, {"id":"IAIN/0052","type":"IAIN","opinion":"2024-11-20","decision":"2025-03-12","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0044","type":"IAIN","opinion":"2024-09-03","decision":"2025-03-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0036/G","type":"II","opinion":"2024-06-27","decision":"2024-09-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Grouped application comprising two variations as follows: C.I.4 – Update of sections 4.4 of the SmPC in order to add immune effector cell-associated neurotoxicity syndrome (ICANS) and ICE scoring in the table for neurologic adverse reaction and update of section 4.8 of the SmPC to add immune effector cell-associated neurotoxicity syndrome (ICANS) as an adverse drug reaction (ADR) with a “not known” frequency based on the cumulative review of MAH safety database and literature. The Package Leaflet is updated accordingly. An updated RMP version 4.1 has been provided including the relevant changes in accordance with the scope of this procedure."}, {"id":"II/0018/G","type":"II","opinion":"2023-12-14","decision":"2024-09-27","affects":["Annex II"],"codes":["B.II.b.2.b","B.II.b.1.c","B.I.a.1.e","B.I.a.1.j","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated to include the new manufacturer of the biological active substance(s) Celgene Corporation."}, {"id":"II/0014","type":"II","opinion":"2023-09-14","decision":"2024-09-27","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 and 5.1 of the SmPC in order to update efficacy information based on final results from studies 017001 and JCAR-017-BCM-001 listed as obligations in the Annex II. These studies aimed to further characterise the long-term efficacy and safety of Breyanzi in patients treated with relapsed or refractory DLBCL, PMBCL, FL3B after two or more lines of systemic therapy. Study 017001 is a phase 1, open-label, single-arm, multicohort, multicenter, seamless design trial, while study JCAR-017-BCM-001 is a phase 2, open-label, single-arm, multicohort, multicenter trial. The Annex II is updated accordingly. The RMP version 3.0 has also been submitted."}, {"id":"II/0005","type":"II","opinion":"2023-03-30","decision":"2023-04-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with Second-line (2L) Transplant Intended (TI) Large B-Cell Lymphoma (LBCL) for BREYANZI, based on interim analyses from pivotal study JCAR017-BCM-003; this is a global randomized multicentre Phase III Trial to compare the efficacy and safety of JCAR017 to standard of care in adult subjects with high-risk, transplant-eligible relapsed or refractory aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM); As a consequence, sections 4.1, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The annex II and Package Leaflet is updated in accordance. The MAH also took the opportunity to implement editorial changes in line to the core SmPC."} ] }, "loncastuximab-tesirine__zynlonta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zynlonta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/zynlonta-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000366108","type":"IB","opinion":"2026-09-10","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.e","Q.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the shelf life or storage - Change to an approved stability protocol of the finished product; Extension of the shelf life of the finished product - Extension of the shelf life of the finished product based on extrapolation of stability data in accordance with relevant stability guidelines"}, {"id":"PSUSA/00011027/202504","type":"PSUSA","opinion":"2025-12-11","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - loncastuximab tesirine"}, {"id":"EMA/R/0000281443","type":"R","opinion":"2025-09-18","decision":"2025-10-24","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation."}, {"id":"PSUSA/00011027/202410","type":"PSUSA","opinion":"2025-05-22","decision":"2025-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - loncastuximab tesirine"}, {"id":"IB/0019","type":"IB","opinion":"2024-09-30","decision":"2025-07-23","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0020","type":"IAIN","opinion":"2024-10-30","decision":"2025-07-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0009","type":"R","opinion":"2023-09-14","decision":"2023-11-15","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0004","type":"IB","opinion":"2023-04-28","decision":"2023-11-15","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"T/0002","type":"T","opinion":"2023-01-25","decision":"2023-03-09","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0001","type":"IAIN","opinion":"2023-01-12","decision":"2023-03-09","affects":["SmPC","Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "lorlatinib__lorviqua": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lorviqua-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lorviqua-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00010760/202509","type":"PSUSA","opinion":"2026-04-23","decision":"2026-06-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"EURD: PSUSA/00010760/202509 Active"}, {"id":"EMA/VR/0000292366","type":"II","opinion":"2026-02-26","decision":"2026-04-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet due to new quality, preclinical, clinical or pharmacovigilance data Variation type II Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to update dosing recommendations in patients with moderate and severe hepatic impairment based on final results from study B7461040 listed as a category 3 study in the RMP; this is a Phase 1, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Plasma Pharmacokinetics and Safety of Lorlatinib in Participants with Moderate and Severe Hepatic Impairment Relative to Participants with Normal Hepatic Function. The Package Leaflet is updated accordingly."}, {"id":"R/0040","type":"R","opinion":"2025-02-27","decision":"2025-05-08","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0038","type":"IAIN","opinion":"2024-07-29","decision":"2025-03-20","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"R/0031","type":"R","opinion":"2024-01-25","decision":"2024-04-05","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010760/202303","type":"PSUSA","opinion":"2023-11-09","decision":"2024-01-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lorlatinib"}, {"id":"R/0025","type":"R","opinion":"2023-01-26","decision":"2023-04-04","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"R/0019","type":"R","opinion":"2022-01-27","decision":"2022-04-04","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0018","type":"N","opinion":"2021-10-25","decision":"2022-01-27","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0015","type":"II","opinion":"2021-12-16","decision":"2022-01-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor based on results from the phase III randomised CROWN (1006) study listed as a specific obligation (SOB) in the Annex II; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package leaflet is updated accordingly. Version 4.1 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to include minor editorial changes in the PI."}, {"id":"II/0013","type":"II","opinion":"2021-06-24","decision":"2021-07-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to include hypertension and hyperglycaemia as new adverse drug reactions (ADRs) with frequency common and very common respectively together with recommended dose modifications and warnings, based on data from Phase 3 study B7461006, comparing lorlatinib versus crizotinib for the first line treatment of advanced ALK-positive NSCLC. The Package Leaflet is updated accordingly. The RMP version 2.1 has also been submitted."}, {"id":"N/0010","type":"N","opinion":"2020-11-27","decision":"2021-03-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0009/G","type":"II","opinion":"2021-01-28","decision":"2021-03-09","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to change the posology recommendations in patients with severe renal impairment based on the results from Study B7461010 (a phase 1, single dose open-label study to evaluate the pharmacokinetics of lorlatinib in subjects with impaired renal function). The package leaflet has been updated accordingly."}, {"id":"II/0008","type":"II","opinion":"2020-11-12","decision":"2020-12-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to replace the term “Hallucinations” with the new term “Psychotic effects” and to include the new term of “mental status changes” as adverse drug reactions (ADRs) further to the cumulative review of the data available through Clinical Databases and Safety Database. The package leaflet has been updated accordingly."}, {"id":"II/0002","type":"II","opinion":"2020-04-02","decision":"2020-12-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to further reflect the induction potential of lorlatinib on CYP2C9, P-gp, CYP2B6 and UGT1A1 substrates based on the results from the drug-drug interaction sub-study of B7461001. Furthermore, the Marketing authorisation holder (MAH) corrected information regarding ADRs in section 4.8 of the SmPC and added clarification regarding linearity/non-linearity of lorlatinib PK in section 5.2 of the SmPC. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1."}, {"id":"IB/0003","type":"IB","opinion":"2019-12-04","decision":"2020-04-03","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0001","type":"IB","opinion":"2019-08-01","decision":"2020-04-03","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Other variation"} ] }, "lurbinectedin__zepzelca": { "source": [], "procedures": [] }, "lutetium-177lu-oxodotreotide__lutathera": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lutathera-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lutathera-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000367921","type":"N","opinion":"2026-08-13","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives. Marketing Authorisation"}, {"id":"EMA/T/0000349423","type":"T","opinion":"2026-06-15","decision":"2026-07-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation from Advanced Accelerator Applications to Novartis Europharm Limited"}, {"id":"II/0058","type":"II","opinion":"2025-10-21","decision":"2025-11-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","4.8","5.1","5.2"],"scope":"To update sections 4.2, 4.8, 5.1, 5.2 and 11 of the SmPC to update the efficacy and safety information based on primary analysis results from study CAAA601A32201 (NETTER-P) as well as results from modelling and simulation analysis of PK and dosimetry data of Lutathera in adolescents. NETTER-P study is a Phase II, multicenter open-label study which evaluated the safety and dosimetry of Lutathera in adolescent patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and pheochromocytoma and paragangliomas (PPGLs). The package leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"N/0059","type":"N","opinion":"2025-01-10","decision":"2025-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0056","type":"N","opinion":"2024-09-26","decision":"2025-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0049","type":"N","opinion":"2024-03-19","decision":"2025-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0048","type":"II","opinion":"2024-05-02","decision":"2025-04-23","affects":["SmPC","PL"],"codes":["B.I.a.1.g"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Introduction of a new manufacturer of the AS that is not supported by an ASMF and requires significant update to the relevant AS section in the dossier"}, {"id":"EMA/N/0000263398","type":"N","opinion":"2025-04-03","decision":"2025-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"EMA/N/0000253874","type":"N","opinion":"2025-03-03","decision":"2025-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"N/0045","type":"N","opinion":"2023-09-19","decision":"2024-01-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0038","type":"II","opinion":"2023-04-20","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of sections 2, 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 4.9, 5.1, 5.2, 5.3, 6.2, 6.4, 6.5, 6.6, 11 and 12 of the SmPC to align the Lutathera product information to the latest Core Data Sheet (CDS) version 2.0 (changes to the CDS based on data from the Lutathera existing dossier, current medical practice and new literature). Annex IIIA and the package leaflet are updated accordingly. In addition, additional corrections and changes are made throughout the product information (PI) to comply with the latest QRD template and to improve the language."}, {"id":"IAIN/0041","type":"IAIN","opinion":"2023-02-10","decision":"2024-01-25","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUSA/00010643/202112","type":"PSUSA","opinion":"2022-07-21","decision":"2022-09-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lutetium (177Lu) oxodotreotide"}, {"id":"R/0032","type":"R","opinion":"2022-05-19","decision":"2022-07-08","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0030","type":"II","opinion":"2022-03-24","decision":"2022-07-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of the SmPC sections 4.4, 4.8, 5.1 based on the pivotal Phase III study, NETTER-1. Additionally, updates are proposed in the PI to correct some information based on currently approved data. The MAH also took the opportunity to add some minor editorial changes in the PI. The PL is updated accordingly. The MAH took also the opportunity to update the details of all local representatives in the PL. The RMP v. 2.0 has been submitted."}, {"id":"IA/0033/G","type":"IA","opinion":"2022-02-09","decision":"2022-07-08","affects":["Annex II","PL"],"codes":["B.I.a.2.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0022","type":"II","opinion":"2020-12-10","decision":"2021-01-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.6","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.5, 4.6, 4.8 and 5.1 of the SmPC in order to introduce structural changes in the dosing and administration and warnings and precautions section, include clarifications in the pregnancy and overdose sections, update instructions for use based on end user feedback and update of amino acid solution information based on review and approval of LysaKare; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to include correction of typographical errors and editorial changes in the PI in line with the latest QRD template version 10.1."}, {"id":"PSUSA/00010643/201906","type":"PSUSA","opinion":"2020-01-30","decision":"2020-04-01","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - lutetium (177Lu) oxodotreotide"}, {"id":"N/0008","type":"N","opinion":"2018-12-17","decision":"2019-03-25","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0005","type":"II","opinion":"2019-01-31","decision":"2019-03-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the SmPC section 5.1 to include information on the quality of life based on relevant analyses of NETTER-I study data."}, {"id":"IAIN/0003","type":"IAIN","opinion":"2018-03-21","decision":"2019-03-25","affects":["Annex II","Labelling","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"} ] }, "lutetium-177lu-vipivotide-tetraxetan__pluvicto": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/pluvicto-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/pluvicto-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000361057","type":"N","opinion":"2026-07-20","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representative."}, {"id":"EMA/VR/0000325276","type":"IB","opinion":"2026-02-17","decision":"2026-05-11","affects":["SmPC"],"codes":["C.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update Section 11 (Table 4) of the SmPC to correct the dosimetry data."}, {"id":"EMA/N/0000306844","type":"N","opinion":"2025-10-17","decision":"2026-05-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representative."}, {"id":"EMA/N/0000257727","type":"N","opinion":"2025-03-25","decision":"2026-05-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"EMA/N/0000244915","type":"N","opinion":"2025-02-10","decision":"2026-05-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"II/0022","type":"II","opinion":"2025-05-08","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.6","4.8"],"scope":"Update of section 4.2, 4.4., 4.6 and 4.8 of the SmPC based on final results from study PSMA-617-01 (CAAA617A12301 – VISION) listed as a category 3 study in the RMP; this is an international, prospective, open-label, multicenter, randomized Phase 3 study of 177Lu-PSMA-617 in the treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer. The Package Leaflet is updated accordingly. The RMP version 2.0 has also been submitted. In addition, the MAH took the opportunity to implement editorial changes to the PI."}, {"id":"N/0021","type":"N","opinion":"2024-09-26","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0015","type":"N","opinion":"2024-04-26","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0012","type":"N","opinion":"2023-11-27","decision":"2024-04-19","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0009","type":"N","opinion":"2023-10-18","decision":"2024-04-19","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0001","type":"N","opinion":"2023-01-30","decision":"2024-04-19","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0004/G","type":"IB","opinion":"2023-04-19","decision":"2024-04-19","affects":["Annex II","Labelling","PL"],"codes":["B.II.b.2.c.2","B.II.b.1.a","B.I.a.1.z","B.II.b.1.f","B.II.b.1.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Other variation; Replacement or addition of a manufacturing site for part or all of the manufacturing process of the FP - Site where any manufacturing operation(s) take place, except batch release, batch control, and secondary packaging, for sterile medicinal products (including those that are aseptically manufactured) excluding biological/ immunological medicinal products."}, {"id":"N/0014","type":"N","opinion":"2024-03-20","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "midostaurin__rydapt": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/rydapt-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/rydapt-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000320179","type":"IA","opinion":"2026-01-13","decision":null,"affects":["Annex II","PL"],"codes":["A.7","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release"}, {"id":"IAIN/0036/G","type":"IAIN","opinion":"2024-12-11","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0035/G","type":"IAIN","opinion":"2024-06-26","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0029","type":"II","opinion":"2023-06-22","decision":"2023-09-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add “Acute febrile neutrophilic dermatosis” to the list of adverse drug reactions (ADRs) with frequency not known based on pre-clinical data, clinical trial datasets, scientific literature and safety databases. The Package Leaflet is updated accordingly. The MAH took the occasion to also include some editorial/formatting changes in the Product information. The MAH has also taken the occasion to align the annex A to the correct expression of pack size as included in the registered system (Siamed)."}, {"id":"II/0028","type":"II","opinion":"2023-03-30","decision":"2023-09-18","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update efficacy and safety information in elderly patients based on final results from study CPKC412A2408 - An open-label, multi-center, Phase IIIb study to assess the safety and efficacy of midostaurin (PKC412) in patients 18 years of age or older with newly diagnosed FLT3-mutated Acute Myeloid Leukemia who are eligible for “7+3” or “5+2” chemotherapy, listed as a PAES in the Annex II. The RMP version 8.1 has also been submitted."}, {"id":"II/0024","type":"II","opinion":"2022-09-15","decision":"2023-09-18","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study CPKC412E2301 listed as an obligation in the Annex II of the Product Information. This is a Phase III study to investigate the efficacy in elderly patients. A final pharmacogenomic report is also provided to fulfil MEA004. The Annex II and the RMP (submitted version 7.0) are updated accordingly."}, {"id":"R/0023","type":"R","opinion":"2022-03-24","decision":"2022-05-30","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0022","type":"II","opinion":"2021-12-16","decision":"2022-03-04","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information in elderly patients, based on final results from study ADE02T listed as PAES in the Annex II; this is a phase II study to investigate the efficacy of midostaurin in combination with intensive induction, consolidation including allogenic SCT and single agent maintenance in patients aged 18-70 with FLT3 ITD mutated AML."}, {"id":"II/0018/G","type":"II","opinion":"2022-01-27","decision":"2022-03-04","affects":["SmPC","PL"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.1","5.2"],"scope":"Section 4.2 Under Hepatic impairment it is added that “Exposure to midostaurin and its active metabolite CGP62221 is substantially lower in patients with severe hepatic impairment than that in patients with normal hepatic function (see section 5.2). However, there are insufficient efficacy data in patients with severe hepatic impairment to suggest a dose adjustment is required.” The relevant warning is removed from section 4.4. Section 4.5 Information in section “Effect of Rydapt on other medicinal products” is updated to reflect new information."}, {"id":"PSUSA/00010638/202010","type":"PSUSA","opinion":"2021-06-24","decision":"2021-08-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - midostaurin"}, {"id":"II/0014","type":"II","opinion":"2020-12-10","decision":"2021-01-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.1"],"scope":"Update of sections 4.2, and 4.4 of the SmPC in order to change posology recommendations and add Special warnings and precautions for use in Paediatric population following the occurrence of severe dose limiting toxicities (DLTs) in the pediatric study CPKC412A2218 which is currently on clinical hold. The study is part of the agreed PIP (EMEA-000780-PIP01-09-M05) for which a Request for Modification was submitted on 20-Apr-2020. Section 5.1 of the SmPC and the Package Leaflet are updated accordingly. The RMP version 5.0 has also been submitted. In addition, the MAH takes this opportunity to introduce minor editorial changes to align the PI to the updated QRD template version 10.1."}, {"id":"IB/0013","type":"IB","opinion":"2020-06-25","decision":"2021-01-22","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0002","type":"II","opinion":"2018-04-26","decision":"2019-04-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","4.6","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to reflect the results from study R1701192 “In vitro assessment of cytochrome P450 3A4 and 3A5 enzyme inhibition by midostaurin, CGP52421 and CGP62221” and update of section 5.2 of the SmPC to reflect the results from study R1600721 “Assessment of midostaurin and its metabolites (CGP052421 and CGP062221) as inhibitors of human bile salt export pump (BSEP)\", in fulfilment of the post-authorisation measures MEA 011 and REC 014."}, {"id":"T/0003","type":"T","opinion":"2018-03-20","decision":"2018-04-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0001","type":"IB","opinion":"2017-11-15","decision":"2018-04-30","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "mirdametinib__ezmekly": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ezmekly-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000363326","type":"IB","opinion":"2026-09-03","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol)"}, {"id":"EMA/VR/0000371059","type":"IAIN","opinion":"2026-09-02","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition or replacement of a site responsible for batch release (QP certification) - Not including batch control/testing"}, {"id":"EMA/VR/0000363069","type":"IAIN","opinion":"2026-08-12","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.1.a","Q.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation"}, {"id":"EMA/VR/0000313332","type":"II","opinion":"2026-03-12","decision":"2026-04-23","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"A grouped application consisting of: Update of section 5.2 of the SmPC in order to introduce the results from the in vitro study KC245128 investigating the reversible inhibitory potential of mirdametinib and PD-0315209 on CYP2C8, CYP2C9, CYP2C19, CYP1A2, CYP2D6, and CYP3A4. Update of section 5.2 of the SmPC in order to introduce the results from the in vitro study KC255037 investigating the potential inhibitory effect of PD-0315209 on UGT enzymes. Update of section 5.2 of the SmPC in order to introduce the results from the in vitro studies KC245140 and KC248110 investigating the CYP enzyme and transporter inhibitory potential of M22."}, {"id":"EMA/T/0000334329","type":"T","opinion":"2026-03-27","decision":"2026-04-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from SpringWorks Therapeutics Ireland Limited to Merck Europe B.V."} ] }, "mirvetuximab-soravtansine__elahere": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/elahere-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/elahere-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000323227","type":"IAIN","opinion":"2026-01-22","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Secondary packaging site; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/VR/0000286590","type":"IB","opinion":"2025-08-20","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To propose changes in sections 1, 2, 3, 4, 5 and 6 of the Package Leaflet following an assessment carried out on target patient groups. The MAH took the opportunity to make some editorial changes in the SmPC and additional editing amendments have been carried out in FI, DE, NO, PL, SL, ES and LT annexes. In addition, Annex II has been amended by reporting the correct manufacturer of the biological active substance: Bsp Pharmaceuticals S.p.A, Via Appia Km 65561, Latina Scalo, LT 04013 Italy. Finally, an editorial correction has been performed in the contact details of the Icelandic local representative in section 6 of the PL."} ] }, "mogamulizumab__poteligeo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/poteligeo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/poteligeo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000340939","type":"II","opinion":"2026-09-17","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to amend the Special warnings and precautions for use based on the data from three non-interventional real-world studies among mycosis fungoides and Sézary syndrome patients, also the post-marketing data and literature review. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"EMA/VR/0000339221","type":"IAIN","opinion":"2026-04-08","decision":"2026-06-19","affects":["Annex II","PL"],"codes":["Q.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition or replacement of a site responsible for batch release (QP certification) - Not including batch control/testing"}, {"id":"EMA/VR/0000273196","type":"IAIN","opinion":"2025-05-21","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update section 4.8 of the SmPC and section 4 of the PL following the PRAC signal assessment for colitis"}, {"id":"IAIN/0024","type":"IAIN","opinion":"2024-05-13","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0021","type":"R","opinion":"2023-06-22","decision":"2023-09-01","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IA/0016","type":"IA","opinion":"2022-04-25","decision":"2023-04-24","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0010/G","type":"II","opinion":"2021-03-25","decision":"2022-04-29","affects":["SmPC","Annex II","PL"],"codes":["C.I.z","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","4.8"],"scope":"Update section 4.8 of the SmPC with the submission of data from Study 0761-010 for ADA based on the revised assay as requested by the CHMP in order to review the revised data, and a reanalysis of the effect of ADA on safety, efficacy and mogamulizumab PK of subjects previously considered “inconclusive” now resulting in ADA positive. Update of section 4.6 to remove the statement on contraception requirements for male subjects/patients from the product information. The PL is updated accordingly. The MAH took the opportunity to update the PI in accordance with the QRD template v10.1."}, {"id":"IB/0011","type":"IB","opinion":"2021-06-23","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IA/0014","type":"IA","opinion":"2021-12-13","decision":"2022-04-29","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0003/G","type":"IAIN","opinion":"2019-11-06","decision":"2020-10-19","affects":["Annex II","PL"],"codes":["A.4","A.5.b","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Replacement or addition of a manufacturing site for the FP - Secondary packaging site."} ] }, "momelotinib__omjjara": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/omjjara-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/omjjara-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000307131","type":"II","opinion":"2026-04-10","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add erythema multiforme and hypersensitivity to the list of adverse drug reactions (ADRs) based on postmarketing data. The Package Leaflet is updated accordingly. In addition, the MAH implement editorial changes to the PI."}, {"id":"II/0004/G","type":"II","opinion":"2025-03-27","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4","C.I.z","A.6"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"A grouped application comprised of one Type II, one Type IB and one Type IA Variation, as follows: Type II (C.I.4): Update of section 4.8 of the SmPC in order to add 'rash' to the list of adverse drug reactions (ADRs) with frequency 'common' based on a safety review of clinical studies and post-marketing safety data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to add editorial changes to the PI and update the list of local representatives in the Package Leaflet."} ] }, "mosunetuzumab__lunsumio": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lunsumio-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lunsumio-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00010999/202512","type":"PSUSA","opinion":"2026-07-23","decision":"2026-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - mosunetuzumab"}, {"id":"EMA/VR/0000343033","type":"II","opinion":"2026-07-09","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to update the existing warning on serious infections to add information regarding progressive multifocal leukoencephalopathy (PML), based on a safety review. The Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000350590","type":"IB","opinion":"2026-06-30","decision":null,"affects":["Annex II"],"codes":["C.9.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the RMP and section E of the Annex II of the Product Information to propose a change of the due date of the Specific Obligation #1 (to provide the results of Study GO42909) from 'Q3 2026' to 'Q1 2028'."}, {"id":"X/0015","type":"X","opinion":"2025-09-18","decision":"2025-11-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"R/0014","type":"R","opinion":"2025-02-27","decision":"2025-04-14","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010999/202312","type":"PSUSA","opinion":"2024-07-25","decision":"2024-09-19","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - mosunetuzumab"}, {"id":"IB/0011/G","type":"IB","opinion":"2024-04-17","decision":"2024-09-19","affects":["SmPC"],"codes":["B.II.g.5.c","B.I.b.2.a","B.II.d.2.a","B.I.b.2.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product; Change in test procedure for AS or starting material/reagent/intermediate - Minor changes to an approved test procedure; Change in test procedure for the finished product - Minor changes to an approved test procedure; Change in test procedure for AS or starting material/reagent/intermediate - Other variation"}, {"id":"IB/0009/G","type":"IB","opinion":"2024-04-17","decision":"2024-09-19","affects":["Annex II"],"codes":["B.I.a.2.a","B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"PSUSA/00010999/202306","type":"PSUSA","opinion":"2024-01-25","decision":"2024-03-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - mosunetuzumab"}, {"id":"IB/0007/G","type":"IB","opinion":"2023-10-19","decision":"2024-03-21","affects":["SmPC"],"codes":["B.II.f.1.b.5","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0001","type":"R","opinion":"2023-02-23","decision":"2023-04-19","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation. Changes were also made to the PI to bring it in line with the current Agency/QRD template, SmPC guideline and other minor editorial changes have been implemented."} ] }, "nadofaragene-firadenovec__adstiladrin": { "source": [], "procedures": [] }, "neratinib__nerlynx": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/nerlynx-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/nerlynx-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000265110","type":"IB","opinion":"2025-05-22","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update sections 1, 2, 3 and 4 of the PL to ensure alignment of the information with the approved sections of the SmPC, as well as to add some key information to improve understanding by the patients. In addition, some linguistic improvements have been included in the French translation of the PI and the date of latest renewal has been included in section 9 of the SmPC."}, {"id":"R/0031","type":"R","opinion":"2023-03-30","decision":"2023-05-26","affects":["SmPC","Annex II","Labelling"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0029","type":"II","opinion":"2022-11-10","decision":"2023-05-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to add information on distribution and on the effect of neratinib on CYP substrates based on non-clinical studies XT218036 and 20325317; Study XT218036 was designed to evaluate neratinib as a substrate of the human transporters OATP1B1 and OATP1B3 and study 20325317 objective was to determine the inactivation kinetic constants (kinact and KI) of Neratinib and M6 for the human cytochrome P450 (CYP) isoenzymes 2B6 and 3A4 using pooled human liver microsomes (HLM). In addition, MAH is also taking this opportunity to introduce editorial changes."}, {"id":"PSUSA/00010712/202107","type":"PSUSA","opinion":"2022-02-24","decision":"2022-04-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - neratinib"}, {"id":"IAIN/0028","type":"IAIN","opinion":"2022-01-24","decision":"2022-04-25","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0021","type":"II","opinion":"2021-09-02","decision":"2021-10-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3","6.6"],"scope":"Update of sections 5.3 and 6.6 of the SmPC based on an updated environmental risk assessment including ERA studies."}, {"id":"II/0015","type":"II","opinion":"2020-10-15","decision":"2021-10-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include final OS results from study 3144A2-3004-WW, a randomised, double-blind, placebo-controlled trial of neratinib after trastuzumab in women with early-stage HER-2/neu overexpressed/amplified breast cancer. The MAH has also taken the opportunity to make some corrections in the SmPC and package leaflet."}, {"id":"IA/0023","type":"IA","opinion":"2021-05-19","decision":"2021-10-25","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"To change the ATC Code of neratinib from L01XE45 to L01EH02."}, {"id":"N/0010","type":"N","opinion":"2020-01-16","decision":"2020-07-27","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0011/G","type":"II","opinion":"2020-06-25","decision":"2020-07-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.3","4.4","4.5","5.2"],"scope":"Update of sections 4.2, 4.3, 4.4, 4.5 and 5.2 of the SmPC in order to update the pharmacokinetics properties of neratinib and amend drug-drug interaction (DDI) information with CYP3A4/P-gp inducers and inhibitors based on two ADME studies (PUMA-NER-0105 and PUMA-NER-0102), a PBPK model report and in vitro studies; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make minor corrections to the PI and to bring the PI in line with the latest QRD template version 10 and SmPC Guideline."}, {"id":"II/0007","type":"II","opinion":"2019-12-12","decision":"2020-07-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of section 5.1 of the SmPC to update the results of the multicentre, randomised, double-blind, placebo-controlled, pivotal phase III study, ExteNET (3004) in women with early-stage HER2-positive breast cancer who had completed adjuvant treatment with trastuzumab, based on a re-analysis conducted with corrected stratification factors. Furthermore, the MAH took the opportunity to make some corrections in section 4.4 of the SmPC."}, {"id":"IB/0004","type":"IB","opinion":"2019-09-27","decision":"2020-07-27","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0006/G","type":"IAIN","opinion":"2019-10-02","decision":"2020-07-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.5.b","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0003","type":"T","opinion":"2019-06-11","decision":"2019-07-04","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"T/0001","type":"T","opinion":"2019-03-15","decision":"2019-03-28","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "nilotinib__tasigna": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tasigna-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tasigna-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000318973","type":"IA","opinion":"2025-12-17","decision":null,"affects":["Annex II","PL"],"codes":["A.7","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release"}, {"id":"IAIN/0128/G","type":"IAIN","opinion":"2024-11-28","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0122/G","type":"IAIN","opinion":"2023-11-24","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.1.b","B.II.b.1.a","B.II.b.2.c.1","B.II.e.2.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in the specification parameters and/or limits of the immediate packaging of the finished product - Addition of a new specification parameter to the specification with its corresponding test method"}, {"id":"II/0115/G","type":"II","opinion":"2022-05-19","decision":"2023-06-13","affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the ADRs frequency category based on pooled safety data from 13 interventional clinical studies, 5 of which have not been previously assessed (CAMN107A2303 - 120 months data; CAMN107A2404; CAMN107E2401; CAMN107ECN02 and CAMN107EIC01). In addition, the MAH took the opportunity to merge the current 2 SmPCs (one for 150mg and one for 50mg/200mg) into one single SmPC, by including all information from the 150mg SmPC into the 50mg/200mg SmPC; and to implement editorial changes. The Package Leaflet is proposed to be updated accordingly. A.6: Update of nilotinib ATC code based on the last update of the WHO ATC index."}, {"id":"II/0109","type":"II","opinion":"2021-06-24","decision":"2022-03-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of SmPC sections 4.4, 4.8, 5.1 based on the 5-year follow up data from the study CAMN107A2203 in paediatric patients. Annex II D has been updated to reflect the fulfilment of the obligation to conduct the post authorisation efficacy study (PAES). The Package leaflet is updated accordingly. In addition, the Tasigna EU RMP version 25 has been updated to remove the corresponding additional pharmacovigilance activity and the missing information ‘Long-term follow-up in paediatric patients’."}, {"id":"II/0107","type":"II","opinion":"2021-03-11","decision":"2022-03-28","affects":["SmPC"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of the 5 year data including data on late relapses from the ongoing studies ENESTfreedom (CAMN107I2201): A Phase II, single-arm, open-label, multicenter nilotinib TFR study in patients with BCR-ABL1 positive CML-CP, who had achieved durable minimal residual disease (MRD) status on first-line nilotinib treatment and ENESTop (CAMN107A2408): A Phase II, single-arm, open-label, multicenter study, evaluating TFR in patients with BCR-ABL1-positive CML-CP who achieved a sustained molecular response of MR4.5 on nilotinib treatment after switching from imatinib to nilotinib."}, {"id":"IAIN/0111/G","type":"IAIN","opinion":"2021-05-05","decision":"2022-03-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.e.6.b","B.II.e.1.b.3","B.II.b.2.c.1","B.II.b.1.b","B.II.b.1.a","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that does not affect the product information; Change in immediate packaging of the finished product - Change in type/addition of a new container - Deletion of an immediate packaging container without a complete deletion of a strength or pharmaceutical form; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Primary packaging site."}, {"id":"PSUSA/00002162/202001","type":"PSUSA","opinion":"2020-09-17","decision":"2020-11-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nilotinib"}, {"id":"II/0106","type":"II","opinion":"2020-09-03","decision":"2020-11-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of the section \"4.8 Undesirable effects\" of the SmPC with 'Facial paralysis' with the frequency unknown. Section \"4 possible side effects\" of the package leaflet has been updated accordingly. The QRD template version 10.1 has been implemented as part of this PI update. The Annex III has been updated accordingly. Editorial changes have been made to the Annex II to follow the new QRD template."}, {"id":"IAIN/0102/G","type":"IAIN","opinion":"2020-03-09","decision":"2020-11-16","affects":["Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0101","type":"IAIN","opinion":"2019-12-11","decision":"2020-11-16","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00002162/201901","type":"PSUSA","opinion":"2019-09-19","decision":"2019-11-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nilotinib"}, {"id":"II/0095","type":"II","opinion":"2018-07-19","decision":"2019-07-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.6","4.8","6.1"],"scope":"Update of section 4.6 of the SmPC to include the recommendation that women should not breast-feed during Tasigna treatment and for 2 weeks after the last dose. The Package Leaflet has been updated accordingly. Further, the MAH took the opportunity to implement minor editorial changes, corrections and/or additions in the SmPC and Package Leaflet based on data already submitted and assessed previously, including the alignment of section 4 of the Package Leaflet with section 4.8 of the SmPC, the completeness of the list of excipients in SmPC section 6.1 and minor changes to SmPC sections 4.4 and 4.5."}, {"id":"II/0092","type":"II","opinion":"2018-07-12","decision":"2019-07-11","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of an updated RMP version 21.1 in order to delete the important identified risk 'Myelosuppression', to implement changes in the definition of the identified risks 'Hepatotoxicity' and 'Fluid retention', and to reflect the discontinuation of the educational material as additional risk minimisation measure. Annex II has been updated accordingly."}, {"id":"T/0094","type":"T","opinion":"2018-03-26","decision":"2018-04-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"X/0088/G","type":"X","opinion":"2017-09-14","decision":"2017-11-15","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0084/G","type":"II","opinion":"2017-04-21","decision":"2017-05-24","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","4.4","4.6","4.8","5.1","6.6"],"scope":"Update of sections 4.2, 4.4, 4.6, 4.8, 5.1 and 6.6 of the SmPC based on the results from: - Study CAMN107I2201 (ENESTfreedom: A Phase II, single-arm study evaluating nilotinib treatment discontinuation (treatment-free remission (TFR)) in newly-diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP) who achieved a sustained deep molecular response; - Study CAMN107A2408 (ENESTop): A Phase II, single-arm study evaluating nilotinib treatment discontinuation (treatment-free remission (TFR)) in patients with Ph+ CML-CP who achieved a sustained deep molecular response on nilotinib treatment after switching from imatinib treatment."}, {"id":"IAIN/0082","type":"IAIN","opinion":"2016-05-11","decision":"2017-05-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0075","type":"II","opinion":"2015-06-25","decision":"2016-06-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to amend the safety information based on the results from a 26-week oral gavage carcinogenicity study in 001178 T. The requested variation proposed amendments to the Summary of Product Characteristics and to the Risk Management Plan (RMP)."}, {"id":"II/0073","type":"II","opinion":"2015-09-24","decision":"2016-06-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of Annex II of the product information with the submission of the results of the pivotal phase III study in adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myelogenous leukaemia in chronic phase (CML-CP) (study CAMN107A2303). In addition, section 5.1 has also been amended. Package leaflet has been updated accordingly. The RMP has also been updated. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct some minor errors."}, {"id":"IB/0076","type":"IB","opinion":"2015-05-27","decision":"2016-06-02","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IAIN/0077","type":"IAIN","opinion":"2015-05-29","decision":"2016-06-02","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"II/0070/G","type":"II","opinion":"2014-12-03","decision":"2014-12-15","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0068","type":"II","opinion":"2014-06-26","decision":"2014-12-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4 and 4.5 of the SmPC further to the results of a drug-drug interaction study using multiple doses of nilotinib in combination with midazolam. The package leaflet is updated accordingly. The MAH also took the opportunity to make editorial changes to sections 4.5 and 5.2 of the SmPC to improve clarity."}, {"id":"II/0067","type":"II","opinion":"2014-06-26","decision":"2014-12-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC further to 60 month data analysis from the phase III multicentre, open-label, randomised study CAMN107A2303 of imatinib versus nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia in chronic phase (CML-CP) (ANX 40.3). The package leaflet has been updated accordingly. Annex II has also been updated in order to correct an inconsistency with the SmPC."}, {"id":"II/0065","type":"II","opinion":"2014-03-20","decision":"2014-12-15","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with regards to fluid retention and oedema and cardiovascular events, further to the request of the PRAC during the assessment of PSUR 8. The Package leaflet is updated accordingly."}, {"id":"II/0064","type":"II","opinion":"2013-12-18","decision":"2014-12-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC to add a recommendation to use highly effective contraception for up to two weeks after ending treatment with Tasigna. The package leaflet is updated accordingly."}, {"id":"II/0062","type":"II","opinion":"2013-12-18","decision":"2014-12-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC with recommendation for monitoring blood glucose levels before and during Tasigna therapy. The package leaflet is updated accordingly. Editorial changes and corrections to the SmPC were also made."}, {"id":"II/0060","type":"II","opinion":"2013-07-25","decision":"2013-12-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC to recommend lipid monitoring prior to initiating Tasigna therapy and as clinically indicated during treatment. The package leaflet is updated accordingly. The product information is also updated in line with QRD template version 9.0. The contact details in the Netherlands are also updated in the list of local representatives in the package leaflet."}, {"id":"II/0058","type":"II","opinion":"2013-05-30","decision":"2013-12-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC further to 48 month data analysis from the phase III multicentre, open-label, randomised study of imatinib versus nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia in chronic phase (CML-CP) (CAMN107A2303). The package leaflet has been updated accordingly. The MAH also proposed minor editorial changes and to update Annex II in line with the latest QRD template (version 8.3). The contact details of the local representative in Croatiahave also been added in the package Leaflet."}, {"id":"II/0051/G","type":"II","opinion":"2013-01-17","decision":"2013-12-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of section 4.5 of the SmPC with regards to the concomitant use of nilotinib and gastric pH-elevating agents. Update of section 5.2 of the SmPC to include study results regarding the relative bioavailability of nilotinib. The Package leaflet is updated accordingly. Annex II has also been updated in line with the latest QRD template version 8.2."}, {"id":"IB/0054","type":"IB","opinion":"2013-01-16","decision":"2013-12-20","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"R/0047","type":"R","opinion":"2012-07-19","decision":"2012-09-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0046","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC further to 36 month data analysis from the phase III multicenter, open-label, randomized study of imatinib versus nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) (CAMN107A2303). The package leaflet has been updated accordingly."}, {"id":"IAIN/0048","type":"IAIN","opinion":"2012-05-03","decision":"2012-06-27","affects":["SmPC"],"codes":["B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"II/0037","type":"II","opinion":"2011-11-17","decision":"2011-12-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of 4.8 of the SmPC in order to add the adverse reaction peripheral arterial occlusive disease with a frequency “uncommon” and to consequently delete the adverse reaction arteriosclerosis obliterans. The Package Leaflet is updated in accordance."}, {"id":"II/0036","type":"II","opinion":"2011-10-20","decision":"2011-11-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the Summary of Product Characteristics with the results of a 2-year oral carcinogenicity study in rats further to the request of the CHMP (FUM 007). The MAH also took the opportunity to update the contact details of the local representatives in Poland and Romania in the package leaflet."}, {"id":"IB/0038/G","type":"IB","opinion":"2011-09-15","decision":"2011-09-15","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"II/0034","type":"II","opinion":"2011-05-19","decision":"2011-06-17","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC and of the Package Leaflet further to 24 month data analysis from the phase III multicenter, open-label, randomized study of imatinib versus nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) (CAMN107A2303). The Risk Management Plan version number (version 9) has also been updated in Annex II."}, {"id":"II/0033","type":"II","opinion":"2011-04-14","decision":"2011-05-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) and the package leaflet with information regarding tumour lysis syndrome. The MAH also took the opportunity to update the contact details of the local representatives in Poland and Romania in the package leaflet."}, {"id":"IA/0035/G","type":"IA","opinion":"2011-05-19","decision":"2011-05-19","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.4.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shape or dimensions of the container or closure (immediate packaging) - Non-sterile medicinal products"}, {"id":"IG/0032/G","type":"IG","opinion":"2010-12-21","decision":null,"affects":["Annex II"],"codes":["C.I.9.c","C.I.9.e","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the Detailed Description of the Pharmacovigilance System (DDPS) to version 9.0, to include: - a change in the deputy of the Qualified Person for Pharmacovigilance (QPPV); - a change in the major contractual arrangements. - administrative changes not impacting the operation of the pharmacovigilance system. Annex II.B has also been updated with the latest wording as per October 2010 CHMP procedural announcement."}, {"id":"X/0028","type":"X","opinion":"2010-09-23","decision":"2010-12-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH submitted an extension application to the marketing authorisation for a new strength: 150 mg hard capsules, in the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) ."}, {"id":"II/0029","type":"II","opinion":"2010-09-23","decision":"2010-12-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3"],"scope":"Extension of indication of Tasigna in the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase. Consequently, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the SmPC and the package leaflet have been updated. Annex II has been updated to included the updated version of the risk management plan (version 8.1). The Marketing Authorisation Holder also took the opportunity to update the product information with the latest QRD template."}, {"id":"II/0031","type":"II","opinion":"2010-07-22","decision":"2010-08-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the Summary of Product Characteristics further to 24-months follow up safety and efficacy data from the Phase II study CAMN107A2101 for patients with imatinib-resistant or intolerant chronic myelogenous leukaemia in chronic phase and in accelerated phase. The final study report for CAMN107A2101 was requested with FUM 032 and FUM033. In addition, a correction to SmPC section 4.4 has been introduced based on these follow-up data. Section 4 of the package leaflet has been updated accordingly. The MAH also took the opportunity to update the list of local representatives in the package leaflet."}, {"id":"II/0027","type":"II","opinion":"2010-02-18","decision":"2010-03-23","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance system (DDPS) to version 8.0, including a change of the Qualified Person for Pharmacovigilance (QPPV). Consequently, Annex II has been updated with the new version number of the agreed DDPS."}, {"id":"II/0026","type":"II","opinion":"2009-11-19","decision":"2009-12-22","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the Summary of Product Characteristics (SPC) with the results of a drug-drug interaction study with warfarin, further to the request of the CHMP (FUM 010). Annex II was also updated in line with the latest QRD template (version 7.3) and the Marketing Authorisation Holder also took the opportunity to update the version number of the Risk Management Plan with the latest agreed version 6. The MAH also took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0018","type":"II","opinion":"2009-07-23","decision":"2009-08-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of section 4.5 of the SPC, with the results from a drug-drug interaction study with esomeprazole (FUM 012). Section 4.4 has been updated accordingly to remove the precautionary statement on concomitant use with antacids, H2 blockers, or proton pump inhibitors. The Package Leaflet has been updated accordingly."}, {"id":"II/0016","type":"II","opinion":"2009-07-23","decision":"2009-08-06","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.9"],"scope":"Update of section 4.9 of the Summary of Product Characteristics further to reports of overdose."}, {"id":"II/0015","type":"II","opinion":"2009-06-25","decision":"2009-08-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Sudden death was identified as a potential risk in February 2006, at which time the Marketing Authorisation Holder of Tasigna (nilotinib) had received 6 reports of sudden and/or unexpected deaths in patients in clinical trials of nilotinib. Further to a cumulative review, a total of 14 cases of sudden cardiac deaths have been identified from clinical trials and compassionate use programs up to the cut-off date of 31 January 2009. The CHMP considered that all fourteen cases identified as sudden cardiac death involve patients who had cardiac disease, either known at the time of study entry or as determined upon autopsy, or who had significant cardiac risk factors."}, {"id":"II/0017","type":"II","opinion":"2009-06-25","decision":"2009-07-27","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the Summary of Product Characteristics to add the term \"myelosuppression\" further to the request from the CHMP in the assessment of the 2nd PSUR."}, {"id":"II/0008","type":"II","opinion":"2009-04-23","decision":"2009-06-08","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4, 4.5 and 5.2 of the SPC with pharmacokinetic results from a study of nilotinib in combination with imatinib, a P-gp substrate, further to the request of the CHMP (FUM 011)."}, {"id":"II/0006","type":"II","opinion":"2009-03-19","decision":"2009-04-21","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of Pharmacovigilance System (DDPS) to version 3.0. Consequently, Annex II of the Product Information is updated with the agreed version number of the DDPS (version 3.0) and the latest agreed version number of the Risk Management plan (version 5.0)."}, {"id":"II/0007","type":"II","opinion":"2009-02-19","decision":"2009-04-07","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.2 and 4.4 of the SPC with the results from a pharmacokinetic study in patients suffering from various degrees of hepatic impairment, further to the request from the CHMP (FUM 016)."}, {"id":"II/0009","type":"II","opinion":"2009-01-22","decision":"2009-02-26","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SPC, further to the request from the CHMP with the results from a drug-drug interaction study with the CYP3A4 inducer rifampicin (FUM 009)."}, {"id":"II/0005","type":"II","opinion":"2008-11-20","decision":"2009-01-05","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SPC further to the request from the CHMP following the assessment of pre- and postnatal development study in rats (FUM 008)."}, {"id":"IB/0002","type":"IB","opinion":"2008-08-04","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"} ] }, "nintedanib__ofev": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ofev-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ofev-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000304681","type":"IB","opinion":"2026-01-05","decision":null,"affects":["SmPC","PL"],"codes":["B.II.b.3.a","B.II.b.5.z","B.II.a.1.a","B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Minor change in the manufacturing process; Change to in-process tests or limits applied during the manufacture of the finished product - Other changes; Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings."}, {"id":"EMA/VR/0000256380","type":"IB","opinion":"2025-03-28","decision":null,"affects":["SmPC","PL"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in the shelf-life or storage conditions of the finished product - Change to an approved stability protocol"}, {"id":"X/0057/G","type":"X","opinion":"2024-12-12","decision":"2025-02-12","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2","6.1","6.3","6.4","6.5"],"scope":"Extension application to add a new strength of 25 mg hard capsules, grouped with an extension of indication (C.I.6.a) in children and adolescents from 6 to 17 years of age. This is based on results from study 1199-0337 (double-blind, randomised, placebo-controlled trial) in paediatric patients from 6 years of age with clinically significant progressive fibrosing Interstitial Lung Disease to evaluate the dose-exposure and safety of nintedanib on top of standard of care for 24 weeks, followed by open label treatment supplemented by an ongoing prospective Phase III extension trial 1199-0378 over at least 2 years."}, {"id":"WS/2701","type":"WS","opinion":"2024-07-04","decision":"2025-02-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add ‘posterior reversible encephalopathy syndrome (PRES)’ to the list of adverse drug reactions (ADRs) with frequency ‘Not known’ based on postmarketing data and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes in the SmPC and update the list of representatives."}, {"id":"IB/0060/G","type":"IB","opinion":"2024-02-27","decision":"2025-02-12","affects":["SmPC","PL"],"codes":["B.II.b.1.e","B.II.b.2.a","B.II.b.3.a","B.II.d.1.d","B.II.b.3.z","B.II.b.5.z","B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings"}, {"id":"X/0052/G","type":"X","opinion":"2023-06-22","decision":"2023-07-28","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1, 5.2 of the SmPC based on results of the trial 1199-0337 (InPedILD) in paediatric patients with clinically significant interstitial lung disease (ILD) and results of a food compatibility study conducted during paediatric development. The Package leaflet is updated accordingly. Consequently, the RMP is updated. Minor QRD changes are also introduced in the labelling. The CHMP reviewed the available paediatric data of studies subject to the agreed Paediatric Investigation Plan P/0438/2021 and the results of these studies are reflected in the Summary of Product Characteristics (SmPC) and, as appropriate, the Package Leaflet."}, {"id":"IG/1463","type":"IG","opinion":"2021-11-18","decision":"2022-10-31","affects":["SmPC","Labelling","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"WS/2027","type":"WS","opinion":"2021-04-09","decision":"2021-08-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"Update of sections 4.2 & 6.6. of the SmPC in order to include an improved method of administration and handling of the capsules, respectively. This update is based on post-marketing experience. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to correct the name of the local representative in Portugal."}, {"id":"PSUSA/00010319/202010","type":"PSUSA","opinion":"2021-06-24","decision":"2021-08-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"II/0040","type":"II","opinion":"2021-05-06","decision":"2021-08-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.8. and 4.4. of the SmPC in order to add “nephrotic range proteinuria” as a new adverse drug reaction with a frequency of “uncommon” for “Idiopathic pulmonary fibrosis (IPF)” and “Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype” and with a frequency of “not known” for “Systemic sclerosis associated interstitial lung disease (SSc-ILD)”and its relevant warning, respectively; the Package Leaflet is updated accordingly."}, {"id":"II/0038","type":"II","opinion":"2020-11-26","decision":"2021-08-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.6","5.2"],"scope":"Update of sections 4.5, 4.6 and 5.2 of the SmPC in order to add drug-drug interaction information with the oral contraceptive Microgynon, a combination of ethynilestradiol and levonorgestrel based on final) based on final results from clinical study No1199-0340. This was a phase I, open-label, 2-period cross-over, fixed-sequence design trial, investigated the effect of multiple oral doses of nintedanib on the single dose kinetics of a combination of ethinylestradiol and levonorgestrel (Microgynon). The Package Leaflet is updated accordingly. The RMP is likewise updated to version 10."}, {"id":"II/0034","type":"II","opinion":"2020-12-10","decision":"2021-08-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of SmPC to include results of a double-blind, randomised, parallel-group trial to evaluate the efficacy and safety of Ofev co-administered with oral sildenafil, compared to treatment with Ofev alone, in patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment (INSTAGE clinical trial)."}, {"id":"PSUSA/00010319/202004","type":"PSUSA","opinion":"2020-11-12","decision":"2021-01-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"II/0033","type":"II","opinion":"2020-11-06","decision":"2021-01-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of SmPC Sections 5.1. to include additional clinical information from an open-label extension trial 1199.33 (INPULSIS-ON) of the pivotal phase III, randomised, double-blind, placebo-controlled studies with identical design (INPULSIS-1 (1199.32) and INPULSIS-2 (1199.34)). This trial provides safety and efficacy data up to 192 weeks."}, {"id":"IG/1293/G","type":"IG","opinion":"2020-10-16","decision":"2021-01-07","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0027","type":"II","opinion":"2020-05-28","decision":"2020-07-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include new indication for OFEV for the treatment of other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype based on the results of pharmacology studies and the double-blind, randomised, placebo-controlled phase III trial (INBUILD). Consequently, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated in order to reflect the use of Ofev in the new indication. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor formatting changes in the PI. Furthermore, the PI is brought in line with the latest QRD template version 10.1. The RMP version 9.1 has also been adopted."}, {"id":"WS/1722","type":"WS","opinion":"2019-12-12","decision":"2020-04-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add alopecia with a frequency uncommon for Ofev and very common for Vargatef; and headache with a common frequency for both Ofev and Vargatef as new adverse drug reactions based on an overall assessment of the safety data for the nintedanib products. The Package Leaflet is updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to include the latest renewal date in the Vargatef SmPC."}, {"id":"II/0026","type":"II","opinion":"2020-02-27","decision":"2020-04-17","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.5","4.6","4.8","5.1","5.2"],"scope":"Extension of Indication to include a new indication for OFEV for the treatment of Systemic Sclerosis associated Interstitial Lung Disease. As a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet. The MAH takes this opportunity to also introduce minor linguistic corrections to the Annexes for France and Sweden. The RMP version 7.2 has also been adopted."}, {"id":"IAIN/0028","type":"IAIN","opinion":"2019-09-27","decision":"2020-04-17","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0025","type":"R","opinion":"2019-07-25","decision":"2019-09-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010319/201810","type":"PSUSA","opinion":"2019-05-29","decision":"2019-07-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"II/0021","type":"II","opinion":"2018-10-31","decision":"2019-07-25","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include ‘myocardial infarction’ as a new adverse drug reaction with a frequency ‘uncommon’ in order to fulfil LEG 004.1, following the assessment of PSUSA/00010319/201704. The Package Leaflet is updated accordingly. The RMP version 6.3 (in revision 2 of the template) is also updated accordingly."}, {"id":"WS/1307","type":"WS","opinion":"2018-04-26","decision":"2018-07-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC for Ofev and Vargatef to amend the current warning on drug induced liver injury based one case of sever liver injury with fatal outcome reported for Ofev during the post-marketing phase. In addition section 4.4 of the Ofev SmPC is updated to include when the majority of the hepatic events occurred and on the need for hepatic transaminases and bilirubin levels to be measured at regular intervals during the first 3 months of treatment. Section 4.8 of the Vargatef SmPC is also updated to include in the summary of the safety profile that the safety data is also based on post-marketing data. The Package Leaflet is updated accordingly."}, {"id":"PSUSA/00010319/201710","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"II/0018/G","type":"II","opinion":"2018-05-17","decision":"2018-07-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1","5.2"],"scope":"Update of section 4.4 in order to amend the current warning on co-administration with pirfenidone and update of section 5.1 to include the results of study 1199.222, a phase IV, 12 week, open label, randomised, parallel group study to evaluate the safety, tolerability and pharmacokinetics of oral nintedanib in combination with oral pirfenidone in comparison with nintedanib alone in patients with idiopathic pulmonary disease (IPF). The Package Leaflet is updated accordingly."}, {"id":"II/0016","type":"II","opinion":"2017-07-20","decision":"2018-07-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.2"],"scope":"Update of section 4.4 of the SmPC to amend the current warning on the hepatic function to include low body weight, Asian origin, female sex and age as factors of increased risk of liver enzymes elevations, update of section 4.8 of the SmPC to revised the frequency of the ADR ‘drug-induced liver injury’ (DILI) from ‘not known’ to ‘uncommon’ and update of section 5.2 of the SmPC to amend the current information related to the mean exposure to nintedanib by race, based on a review of clinical trials and post-marketing data on DILI and on the exposure safety relationship between nintedanib plasma exposure and liver enzyme elevations. The Package Leaflet is updated accordingly."}, {"id":"PSUSA/00010319/201610","type":"PSUSA","opinion":"2017-05-18","decision":"2017-07-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"WS/0998","type":"WS","opinion":"2016-11-10","decision":"2017-01-09","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUSA/00010319/201604","type":"PSUSA","opinion":"2016-11-10","decision":"2017-01-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"II/0006","type":"II","opinion":"2016-07-21","decision":"2016-09-02","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to revise dose recommendations for patients with mild hepatic impairment, based on PK/PD modelling data. In addition, the marketing authorisation holder took the opportunity to bring the Annex II in line with the latest QRD template version 10. Furthermore, the MAH introduced minor linguistic corrections to the Italian product information."}, {"id":"WS/0766","type":"WS","opinion":"2016-01-28","decision":"2016-07-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to include further information related to patients with hepatic impairment based on the CSRs for studies 1199.37, 1199.39 and 1199.200. In addition, the MAH took the opportunity to make editorial changes in the SmPC, labelling and Package Leaflet, to merge the SmPCs for the 100 mg and 150 mg strengths and to update the contact details of the local representative in Portugal in the Package Leaflet. The provision of the CSR of study 1199.200 addresses the post-authorisation measure MEA 001. A revised RMP version was agreed during the procedure; RMP version 2.1 for OFEV and RMP version 3.1 for Vargatef."}, {"id":"PSUSA/00010319/201510","type":"PSUSA","opinion":"2016-05-26","decision":"2016-07-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"}, {"id":"PSUSA/00010319/201504","type":"PSUSA","opinion":"2015-11-19","decision":"2016-01-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (respiratory indication)"} ] }, "nintedanib__vargatef": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vargatef-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/vargatef-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000355233","type":"N","opinion":"2026-06-10","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives and to delete 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4. Additionally, the MAH took the opportunity to introduce minor editorial corrections in the Norwegian translation to align it with the English product information."}, {"id":"WS/2701","type":"WS","opinion":"2024-07-04","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add ‘posterior reversible encephalopathy syndrome (PRES)’ to the list of adverse drug reactions (ADRs) with frequency ‘Not known’ based on postmarketing data and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes in the SmPC and update the list of representatives."}, {"id":"IB/0052/G","type":"IB","opinion":"2024-04-11","decision":null,"affects":["SmPC","PL"],"codes":["B.II.b.1.e","B.II.b.2.a","B.II.b.3.a","B.II.d.1.d","B.II.b.3.z","B.II.b.5.z","B.II.a.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process; Change in the specification parameters and/or limits of the finished product - Deletion of a non-significant specification parameter."}, {"id":"PSUSA/00010318/202210","type":"PSUSA","opinion":"2023-06-22","decision":"2023-08-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"II/0047/G","type":"II","opinion":"2023-06-22","decision":"2023-08-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"N/0042","type":"N","opinion":"2021-10-04","decision":"2022-11-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IG/1463","type":"IG","opinion":"2021-11-18","decision":"2022-11-09","affects":["SmPC","Labelling","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"WS/2027","type":"WS","opinion":"2021-04-09","decision":"2021-10-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"Update of sections 4.2 & 6.6. of the SmPC in order to include an improved method of administration and handling of the capsules, respectively. This update is based on post-marketing experience. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to correct the name of the local representative in Portugal."}, {"id":"II/0038","type":"II","opinion":"2021-02-11","decision":"2021-10-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add nephrotic range proteinuria to the list of adverse drug reactions (ADRs) with frequency Common, following the quarterly signal detection in EudraVigilance/EVDAS and based on MAH assessment of safety data retrieved from all completed ICTs conducted with nintedanib and the MAH Global Drug Safety System (GDSS); the Package Leaflet is updated accordingly."}, {"id":"II/0037","type":"II","opinion":"2021-01-14","decision":"2021-10-11","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study LUME BioNIS listed as an obligation in the Annex II of the Product Information. This is a non-interventional study in patients eligible for treatment with Vargatef to explore whether genetic or genomic markers (alone or combined with clinical covariates) could be used to predict overall survival. The Annex II and the RMP version 8.0 are updated accordingly."}, {"id":"II/0035/G","type":"II","opinion":"2021-01-28","decision":"2021-10-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.6","5.2"],"scope":"Update of sections 4.5, 4.6 and 5.2 of the SmPC to reflect the results of study 1199-0340 conducted in female patients with Systemic Sclerosis associated Interstitial Lung disease (SSc-ILD), to investigate a potential interaction between nintedanib and the oral contraceptive Microgynon, a combination of ethynilestradiol and levonorgestrel. Update of section 4.6 of the SmPC to reflect that patients receiving Vargatef treatment should use highly effective contraceptive methods. The MAH took the opportunity of this variation to implement the QRD template version 10.1 and introduce minor editorial changes to the labelling. The Package Leaflet is updated accordingly."}, {"id":"IG/1293/G","type":"IG","opinion":"2020-10-16","decision":"2021-10-11","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/1722","type":"WS","opinion":"2019-12-12","decision":"2020-07-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add alopecia with a frequency uncommon for Ofev and very common for Vargatef; and headache with a common frequency for both Ofev and Vargatef as new adverse drug reactions based on an overall assessment of the safety data for the nintedanib products. The Package Leaflet is updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to include the latest renewal date in the Vargatef SmPC."}, {"id":"PSUSA/00010318/201910","type":"PSUSA","opinion":"2020-05-28","decision":"2020-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"IAIN/0027","type":"IAIN","opinion":"2019-09-27","decision":"2020-07-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0025","type":"R","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010318/201810","type":"PSUSA","opinion":"2019-05-29","decision":"2019-07-31","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"II/0021","type":"II","opinion":"2018-07-26","decision":"2019-07-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘pruritus’ as a new adverse drug reaction with a frequency ‘common’ following a routine review of post-marketing data. The Package Leaflet is updated accordingly."}, {"id":"IB/0024","type":"IB","opinion":"2019-02-08","decision":"2019-07-31","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"WS/1307","type":"WS","opinion":"2018-04-26","decision":"2018-07-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC for Ofev and Vargatef to amend the current warning on drug induced liver injury based one case of sever liver injury with fatal outcome reported for Ofev during the post-marketing phase. In addition section 4.4 of the Ofev SmPC is updated to include when the majority of the hepatic events occurred and on the need for hepatic transaminases and bilirubin levels to be measured at regular intervals during the first 3 months of treatment. Section 4.8 of the Vargatef SmPC is also updated to include in the summary of the safety profile that the safety data is also based on post-marketing data. The Package Leaflet is updated accordingly."}, {"id":"PSUSA/00010318/201710","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"II/0018","type":"II","opinion":"2017-09-14","decision":"2018-07-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.2"],"scope":"Update of section 4.4 of the SmPC to amend the current warning on hepatic function to include that drug liver induced injury was associated with nintendanib administration, to include low body weight, Asian origin, female sex and age as factors of increased risk of liver enzymes elevations, update of section 4.8 of the SmPC to add ‘drug-induced liver injury’ (DILI) as new ADR with an ‘uncommon’ frequency and update of section 5.2 of the SmPC to amend the current information related to the mean exposure to nintedanib by race, based on a review of clinical trials and post-marketing data on DILI and on the exposure safety relationship between nintedanib plasma exposure and liver enzyme…"}, {"id":"II/0017","type":"II","opinion":"2017-09-14","decision":"2018-07-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘weight decreased’ as a new adverse drug reaction based on a safety review of clinical trials and post-marketing data. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to implement a minor correction in the English product information, minor corrections to the Croatian, Danish, Dutch and Finnish translations and to bring section 4 of the Package Leaflet in line with QRD template version 10."}, {"id":"PSUSA/00010318/201611","type":"PSUSA","opinion":"2017-06-22","decision":"2017-08-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"WS/0998","type":"WS","opinion":"2016-11-10","decision":"2017-02-23","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUSA/00010318/201605","type":"PSUSA","opinion":"2016-12-15","decision":"2017-02-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"II/0009","type":"II","opinion":"2016-09-15","decision":"2017-02-23","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC to amend the current wording on hepatic impairment and to reflect the limited experience in patients with moderate hepatic impairment (Child Pugh B) based on the final clinical study report for study 1199.120: an open label, dose escalation phase I study to evaluate the safety and tolerability of continuous twice-daily oral treatment of nintedanib in Japanese patients with hepatocellular carcinoma. This submission fulfils MEA 003. The RMP has been amended accordingly. In addition the MAH took the opportunity to update the RMP with the required updates requested as part of EMEA/H/C/WS0766."}, {"id":"PSUSA/00010318/201511","type":"PSUSA","opinion":"2016-06-23","decision":"2016-08-18","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nintedanib (oncology indications)"}, {"id":"WS/0766","type":"WS","opinion":"2016-01-28","decision":"2016-03-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to include further information related to patients with hepatic impairment based on the CSRs for studies 1199.37, 1199.39 and 1199.200. In addition, the MAH took the opportunity to make editorial changes in the SmPC, labelling and Package Leaflet, to merge the SmPCs for the 100 mg and 150 mg strengths and to update the contact details of the local representative in Portugal in the Package Leaflet. The provision of the CSR of study 1199.200 addresses the post-authorisation measure MEA 001. A revised RMP version was agreed during the procedure; RMP version 2.1 for OFEV and RMP version 3.1 for Vargatef."}, {"id":"IA/0002","type":"IA","opinion":"2015-04-10","decision":"2016-03-31","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "niraparib__zejula": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zejula-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/zejula-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000296756","type":"II","opinion":"2026-04-23","decision":"2026-06-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the Zejula SmPC and update of sections 4.2, 5.1 and 5.2 of the Jemperli SmPC to include the final results from study 213406 (SCOOP)"}, {"id":"EMA/T/0000303299","type":"T","opinion":"2025-10-15","decision":"2025-11-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from GlaxoSmithKline (Ireland) Limited to GlaxoSmithKline Trading Services Limited"}, {"id":"II/0057/G","type":"II","opinion":"2025-06-19","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0056","type":"II","opinion":"2025-03-27","decision":null,"affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update efficacy and safety information based on the final results from the PRIMA study (PR-30-5017-C), an annex II.D PAES, in order to fulfil ANX 005; this is a phase III, randomised, double-blind, placebo-controlled, multicentre study of niraparib maintenance treatment in patients with advanced ovarian cancer following response on front-line platinum-based chemotherapy. The RMP version 11.0 has also been submitted. In addition, the MAH took the opportunity to implement editorial changes throughout the PI."}, {"id":"N/0051","type":"N","opinion":"2024-01-03","decision":"2024-10-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0047","type":"IB","opinion":"2023-11-06","decision":"2024-10-28","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0049/G","type":"IAIN","opinion":"2023-11-24","decision":"2024-10-28","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.a.1","B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Qualitative and quantitative composition - Solid pharmaceutical forms; Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"II/0037","type":"II","opinion":"2023-04-26","decision":"2023-05-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update recommendations regarding food intake and information on absorption based on results from food effect study 3000-01-004 Stage 3. The package leaflet has been updated accordingly. Furthermore, minor corrections have been made to the product information to reflect that film-coated tablets are provided in blisters. Annex A has been revised accordingly."}, {"id":"II/0033","type":"II","opinion":"2022-12-15","decision":"2023-05-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to amend an existing warning and add MDS/AML to the list of adverse drug reactions (ADRs) with frequency common, and update of section 5.1 based on final results from NOVA study (213356); this is a Phase 3 Randomized double-blind trial of maintenance with niraparib versus placebo in patients with platinum sensitive relapsed ovarian cancer. In addition, the MAH took this opportunity to update sections 4.4 and 4.6 to update information on contraception based on EMA and CTFG recommendations and to make minor editorial changes in the SmPC. The Package Leaflet is updated accordingly. The RMP version 6.0 is approved."}, {"id":"IAIN/0036/G","type":"IAIN","opinion":"2022-06-22","decision":"2023-05-31","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0034","type":"R","opinion":"2022-05-19","decision":"2022-07-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"X/0029","type":"X","opinion":"2022-03-24","decision":"2022-05-30","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"IA/0031","type":"IA","opinion":"2021-08-09","decision":"2022-05-30","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00010655/202009","type":"PSUSA","opinion":"2021-05-20","decision":"2021-07-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - niraparib"}, {"id":"II/0024","type":"II","opinion":"2021-04-22","decision":"2021-06-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to include information and dosing recommendation for patients with moderate hepatic impairment and a warning on the risk of increased exposure of niraparib in patients with severe hepatic impairment based on final results from hepatic study 3000-01-003 (HEPATIC). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to introduce editorial changes in SmPC section 4.4."}, {"id":"IAIN/0027/G","type":"IAIN","opinion":"2021-03-05","decision":"2021-06-01","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0021","type":"II","opinion":"2020-06-25","decision":"2020-10-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.3"],"scope":"Update of section 4.5 of the SmPC in order to add pharmacokinetic interaction information based non-clinical drug-drug interaction (DDI) studies. In addition, the MAH took the opportunity to update section 5.3 of the SmPC in line with the SmPC guideline. The requested variation proposed amendments to the Summary of Product Characteristics."}, {"id":"II/0020","type":"II","opinion":"2020-07-23","decision":"2020-10-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add hypersensitivity, confusional state, and pneumonitis to the list of adverse drug reactions (ADRs) with the frequency “common”, “uncommon” and “uncommon” respectively based on safety evaluations; the Package Leaflet is updated accordingly."}, {"id":"II/0019","type":"II","opinion":"2020-09-17","decision":"2020-10-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the use of Zejula as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The MAH is also taking the opportunity to make minor corrections throughout the PI. The Package Leaflet is updated in accordance."}, {"id":"IAIN/0022/G","type":"IAIN","opinion":"2020-04-30","decision":"2020-10-27","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010655/201909","type":"PSUSA","opinion":"2020-04-30","decision":"2020-06-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - niraparib"}, {"id":"T/0016","type":"T","opinion":"2019-12-19","decision":"2020-01-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0014","type":"IB","opinion":"2019-09-24","decision":"2020-01-31","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUSA/00010655/201809","type":"PSUSA","opinion":"2019-04-26","decision":"2019-06-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - niraparib"}, {"id":"T/0007","type":"T","opinion":"2018-11-12","decision":"2018-12-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0001/G","type":"IB","opinion":"2017-12-19","decision":"2018-12-17","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "niraparib-abiraterone-acetate__akeega": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/akeega-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/akeega-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000282377","type":"II","opinion":"2026-01-29","decision":"2026-03-05","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.3","6.6"],"scope":"Extension of indication to include AKEEGA with prednisone or prednisolone for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) and BRCA1/2 mutations (germline and/or somatic), based on interim results from study 67652000PCR3002 (AMPLITUDE); this is a phase 3 randomized, placebo-controlled, double-blind study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for the treatment of participants with deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC)."}, {"id":"II/0003","type":"II","opinion":"2024-07-11","decision":"2025-06-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"} ] }, "nirogacestat__ogsiveo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ogsiveo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000370753","type":"IAIN","opinion":"2026-08-31","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition or replacement of a site responsible for batch release (QP certification) - Not including batch control/testing"}, {"id":"EMA/VR/0000342459","type":"II","opinion":"2026-07-02","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘hypersensitivity’ to the list of adverse drug reactions (ADRs) with frequency ‘not known’, based on a comprehensive safety review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce a correction to the PI."}, {"id":"EMA/VR/0000325119","type":"II","opinion":"2026-06-11","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Photopsia’, ‘Vitreous floaters’, and ‘Dry eye’ to the list of adverse drug reactions (ADRs) with frequency ‘Common’, based on a safety review regarding eye disorders. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor changes and editorial corrections to the PI, including to the Excipient and the Manufacturer’s information."}, {"id":"EMA/VR/0000296267","type":"IAIN","opinion":"2025-09-23","decision":"2026-04-08","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/T/0000334320","type":"T","opinion":"2026-03-11","decision":"2026-04-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from Springworks Therapeutics Ireland Limited to Merck Europe B.V."} ] }, "nivolumab__opdivo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/opdivo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/opdivo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000372659","type":"IB","opinion":"2026-10-16","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["Q.II.f.1.b.5","Q.II.f.1.e","Q.II.f.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf life of the finished product based on extrapolation of stability data in accordance with relevant stability guidelines; Change in the shelf life or storage - Change to an approved stability protocol of the finished product; Extension of the shelf life of the finished product - After first opening (supported by real time data)"}, {"id":"EMA/VR/0000339488","type":"II","opinion":"2026-07-23","decision":null,"affects":["SmPC"],"codes":["C.3.c"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the outcomes of the Overall Survival (OS) data from the 2nd interim analysis (IA2) from the PAES study CA209274, following the request in the final CHMP Assessment Report for the Post-Authorisation Measure (PAM) procedure (EMA/PAM/0000279604)."}, {"id":"EMA/VR/0000325956","type":"IB","opinion":"2026-03-06","decision":"2026-05-28","affects":["Annex II"],"codes":["C.9.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To amend the due date for the Overall Survival (OS) interim analysis associated with the Post Authorisation Efficacy Study (PAES) CA20976K, as specified in Annex II of the Product Information and in the RMP. The proposed change is from “OS data from the first interim OS analysis” due by 31 March 2029 to “OS data from the 5 year OS analysis” due by 31 May 2027."}, {"id":"EMA/VR/0000304938","type":"II","opinion":"2026-04-23","decision":"2026-05-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include OPDIVO for the treatment of adults and adolescents 12 years of age and older with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL), based on results from the pivotal study CA2098UT (SWOG 1826), a Phase 3, randomised, open-label study of nivolumab + doxorubicin/vinblastine/dacarbazine (N-AVD) versus brentuximab vedotin (Bv) + AVD (Bv-AVD) in patients (age ≥12 years) with newly diagnosed, advanced stage cHL. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 51.2 of the RMP has also been submitted."}, {"id":"EMA/VR/0000333329","type":"II","opinion":"2026-05-07","decision":null,"affects":["Annex II"],"codes":["Q.I.a.1.d","Q.I.b.2.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing site of a starting material/intermediate used in the manufacturing process of the active substance or change in the manufacturing site (including where relevant quality control testing sites) of the active substance - Addition or replacement of a manufacturing site of - a biological active substance or - a biological starting material/reagent/raw material/intermediate used in the manufacture of a biological active substance which may have a significant impact on the quality, safety or efficacy of the finished product or - a material for which an assessment is required of viral safety and/or TSE risk."}, {"id":"EMA/VR/0000319172","type":"II","opinion":"2026-05-07","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add 'Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome' to the table of Recommended treatment modifications, to the special warnings and to the list of adverse drug reactions (ADRs)"}, {"id":"EMA/X/0000304427","type":"X","opinion":"2026-02-26","decision":"2026-04-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to add a new strength of 300 mg solution for injection."}, {"id":"EMA/VR/0000288087","type":"II","opinion":"2025-11-27","decision":"2026-03-05","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.1 and 4.2 of the SmPC following procedure EMEA/H/C/003985/X/0144. In addition, the MAH took the opportunity to update sections 4.4, 4.8, and 5.1 of the SmPC to align it with the new indications and to implement editorial changes to the PI. The Package Leaflet is updated in accordance. The RMP version 46.0 has also been submitted."}, {"id":"EMA/VR/0000285155","type":"IB","opinion":"2025-11-13","decision":"2026-03-05","affects":["Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To extend the due date related to the PAES study CA2098Y8, listed in the Product Information (PI) Annex II and in the RMP from 28.02.2026 to 28.02.2027. In addition, the MAH included the list of local representatives in the labelling for Yervoy."}, {"id":"EMA/VR/0000282199","type":"II","opinion":"2026-01-29","decision":"2026-03-05","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for OPDIVO to include treatment of patients paediatric and adults, with relapsed/refractory classical Hodgkin Lymphoma, based on results from study CA209744; a phase 2, open-label study of nivolumab + brentuximab vedotin for children, adolescents, and young adults with R/R CD30+ classical Hodgkin lymphoma after failure of first-line therapy, followed by brentuximab vedotin + bendamustine for participants with a suboptimal response. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1, 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 44.0 of the RMP has also been submitted"}, {"id":"EMA/VR/0000279319","type":"II","opinion":"2025-10-09","decision":"2026-03-05","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to add the final OS data based on final results from study CA209816. This is a randomized, Open-Label, Phase 3 Trial of Nivolumab plus Ipilimumab or Nivolumab plus Platinum-Doublet Chemotherapy versus Platinum-Doublet Chemotherapy in Early Stage NSCLC. The RMP version 47.0 has also been submitted. In addition, the MAH took the opportunity to update Annex II."}, {"id":"EMA/VR/0000278256","type":"II","opinion":"2025-11-27","decision":"2026-03-05","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report for the final Overall Survival analysis from the post authorisation efficacy study (PAES) CA209577 listed as an obligation in the Annex II of the Product Information. This is a randomized, multicenter, double-blind phase 3 study of adjuvant nivolumab in subjects with resected oesophageal cancer or gastroesophageal cancer who have received chemoradiotherapy followed by surgery. The Annex II and the RMP (version 45.0) are updated accordingly."}, {"id":"X/0144","type":"X","opinion":"2025-03-27","decision":"2025-05-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0140","type":"II","opinion":"2025-03-27","decision":"2025-05-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include OPDIVO in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by monotherapy as adjuvant treatment, for the treatment of resectable non-small cell lung cancer at high risk of recurrence in adult patients whose tumours have PD L1 expression ≥ 1%, based on results from study CA209977T; a phase 3, randomised, double-blind study. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 36.3 of the RMP has also been approved."}, {"id":"PSUSA/00010379/202407","type":"PSUSA","opinion":"2025-02-27","decision":"2025-04-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"WS/2717","type":"WS","opinion":"2025-01-30","decision":"2025-02-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include a new indication for OPDIVO in combination with ipilimumab as first line treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC) based on study CA2099DW. This is a phase 3 randomised, multi-centre, open label study of Nivolumab in combination with Ipilimumab compared to Sorafenib or Lenvatinib as first-line treatment in participants with advanced HCC. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 41.1 of the RMP has also been submitted."}, {"id":"WS/2672","type":"WS","opinion":"2024-11-14","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.6"],"scope":"Extension of indication to include OPDIVO in combination with ipilimumab in the first-line treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) unresectable or metastatic colorectal cancer, based on interim results from study CA2098HW; this is a phase 3 randomised clinical trial of nivolumab alone, nivolumab in combination with ipilimumab, or investigator’s choice chemotherapy in participants with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"IB/0143","type":"IB","opinion":"2024-07-03","decision":"2024-12-19","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0142","type":"IB","opinion":"2024-06-12","decision":"2024-12-19","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0145/G","type":"IAIN","opinion":"2024-06-28","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2597","type":"WS","opinion":"2024-02-15","decision":"2024-05-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to add ‘myelitis’ as a warning under the subsection “Other immune-mediated adverse reactions” and to the list of adverse drug reactions (ADRs) with their calculated frequencies for monotherapy (not known) and in combination (rare), based on post marketing data and literature; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement editorial changes to the SmPC in line with the QRD."}, {"id":"II/0137","type":"II","opinion":"2024-04-25","decision":"2024-05-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include OPDIVO in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma, based on interim results from study CA209901 (CheckMate901). This is a Phase 3, open-label, randomised study of nivolumab combined with ipilimumab, or with standard of care chemotherapy, versus standard of care chemotherapy in participants with previously untreated unresectable or metastatic urothelial cancer. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 35.1 of the RMP has also been submitted."}, {"id":"X/0132","type":"X","opinion":"2024-01-25","decision":"2024-03-25","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_1.(c) Replacement of a biological AS with one of a slightly different molecular structure"}, {"id":"IB/0133","type":"IB","opinion":"2023-10-26","decision":"2024-03-25","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0130","type":"II","opinion":"2023-07-20","decision":"2023-08-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include OPDIVO for the adjuvant treatment of adults and adolescents 12 years of age and older with stage IIB or IIC melanoma who have undergone complete resection, based on results from study CA20976K; This is a phase III, randomized, double-blind study of adjuvant immunotherapy with nivolumab versus placebo after complete resection of stage IIB/C melanoma. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Annex II and Package Leaflet are updated in accordance. Version 33.1 of the RMP has also been submitted."}, {"id":"II/0117","type":"II","opinion":"2023-05-25","decision":"2023-06-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.6"],"scope":"Extension of indication to include OPDIVO in combination with platinum-based chemotherapy for neoadjuvant treatment of adult patients with resectable Stage IB-IIIA non-small cell lung cancer (NSCLC), based on results from study CA209816; a randomised, open-label, phase 3 trial of nivolumab plus ipilimumab or nivolumab plus platinum-doublet chemotherapy versus platinum-doublet chemotherapy in early-stage NSCLC. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 27.4 of the RMP has also been submitted."}, {"id":"II/0125/G","type":"II","opinion":"2023-04-26","decision":"2023-05-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include adolescent patients aged 12 years and older in treatment of advanced (unresectable or metastatic) melanoma (nivolumab monotherapy), treatment of advanced (unresectable or metastatic) melanoma (nivolumab in combination with ipilimumab) and adjuvant treatment of melanoma (nivolumab monotherapy) for Opdivo, based on results from a nonclinical biomarker study (Expression of PD-L1 (CD274), and characterization of tumor infiltrating immune cells in tumors of pediatric origin), also based on results from a Phase 1/2 clinical study (CA209070, A Phase 1/2 Study of Nivolumab (Ind# 124729) In Children, Adolescents, And Young Adults With Recurrent Or Refractory Solid…"}, {"id":"WS/2289","type":"WS","opinion":"2022-09-01","decision":"2023-04-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update sections 4.8 and 5.1 of the SmPC to include 7.5 years of minimum follow-up for all subjects based on addendum 04 Clinical Study Report for Study CA209067; this is a phase 3 randomized, double-blind study of nivolumab monotherapy or nivolumab in combination with ipilimumab versus ipilimumab monotherapy in subjects with previously untreated, unresectable melanoma. MAH has taken the opportunity to introduce minor editorial revisions in the SmPC."}, {"id":"WS/2187","type":"WS","opinion":"2022-10-27","decision":"2023-04-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in alignment with the recommendations made by the CHMP to revise the pooling approach used to describe irARs and tabulated summaries of ADRs following II/0096. Individual study data included within this application has been previously reviewed by the CHMP. The updated Opdivo RMP version 29.0 and Yervoy RMP version 37.0 have also been submitted. The MAH took the opportunity to introduce editorial changes. The Package Leaflet was updated accordingly."}, {"id":"IB/0129","type":"IB","opinion":"2023-03-21","decision":"2023-04-24","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0120","type":"IB","opinion":"2022-04-22","decision":"2023-04-24","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update Annex II of the PI with revised due date related to a PAES study."}, {"id":"IA/0128","type":"IA","opinion":"2023-02-02","decision":"2023-04-24","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"PSUSA/00010379/202107","type":"PSUSA","opinion":"2022-02-24","decision":"2022-04-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"WS/2170","type":"WS","opinion":"2022-01-13","decision":"2022-04-01","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 and 5.1 of the SmPC in order to update efficacy information based on 5 years follow-up OS data from study CA209214; this is a phase 3, randomised, open-label study in previously untreated, intermediate/poor risk advanced RCC."}, {"id":"WS/2153","type":"WS","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","6.6"],"scope":"Update of sections 4.2 and 6.6 of the SmPC to change the infusion time for ipilimumab at a dose of 3 mg/kg from 90 minutes to 30 minutes when used as monotherapy or in combination with nivolumab in the melanoma indications."}, {"id":"WS/2134","type":"WS","opinion":"2021-10-28","decision":"2022-04-01","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8, and 5.1 of the SmPC following based on final results from study CA209908; this is a Phase Ib/II clinical trial of nivolumab monotherapy and nivolumab in combination with ipilimumab in paediatric subjects with high grade primary CNS malignancies; The RMP version 22.4 for Opdivo has also been submitted."}, {"id":"WS/2113","type":"WS","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) with tumour cell PD-L1 expression ≥ 1% for Opdivo in combination with Yervoy; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 26.2 of the Opdivo RMP and version 35.0 of the Yervoy RMP have also been submitted."}, {"id":"II/0107","type":"II","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.6"],"scope":"Extension of indication to include in combination with fluoropyrimidine- and platinum-based combination chemotherapy the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) with tumour cell PD-L1 expression ≥ 1% for OPDIVO based on study CA209648; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 26.2 of the RMP has also been submitted."}, {"id":"II/0106/G","type":"II","opinion":"2021-10-28","decision":"2022-04-01","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.c","B.II.d.1.c","B.II.b.5.a","B.II.b.5.b"],"outcome":"accepted","kind":"other","sections":["4.4","6.5"],"scope":"The SmPC section 2 has been updated as follows: One vial of 12 mL contains 120 mg of nivolumab. The SmPC section 4.4 has been updated as follows: Patients on controlled sodium diet Each mL of this medicinal product contains 0.1 mmol (or 2.5 mg) sodium. This medicinal product contains 10 mg sodium per 4 ml vial, 25 mg sodium per 10 ml vial, 30 mg sodium per 12 ml vial or 60 mg sodium per 24 ml vial, which is equivalent to 0.5%, 1.25%, 1.5% or 3% respectively, of the WHO recommended maximum daily intake of 2 g sodium for an adult."}, {"id":"II/0100","type":"II","opinion":"2022-02-24","decision":"2022-04-01","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for Opdivo to include as monotherapy for the adjuvant treatment of adults with muscle invasive urothelial carcinoma (MIUC) with tumour cell PD-L1 expression ≥ 1%, who are at high risk of recurrence after undergoing radical resection of MIUC (see section 5.1); as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC and Annex II are updated. The Package Leaflet is updated in accordance. Version 26.2 of the RMP has also been submitted."}, {"id":"IB/0115","type":"IB","opinion":"2021-12-07","decision":"2022-04-01","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IAIN/0116/G","type":"IAIN","opinion":"2022-02-09","decision":"2022-04-01","affects":["SmPC","Annex II","PL"],"codes":["A.6","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0105","type":"II","opinion":"2021-09-02","decision":"2021-10-19","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8, and 5.1 of the SmPC based on final results from study CA209205 listed as a PAES in the Annex II; this is a Phase 2, open-label, multi-cohort, single-arm study of nivolumab in patients with classical Hodgkin's Lymphoma; The RMP version 20.3 has also been submitted."}, {"id":"II/0096","type":"II","opinion":"2021-09-16","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","6.6"],"scope":"Extension of indication to use OPDIVO (nivolumab) in combination with fluoropyrimidine- and platinum-based combination chemotherapy, in first-line treatment of adult patients with HER2-negative advanced or metastatic gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinoma whose tumours express PD-L1 with a combined positive score (CPS) ≥ 5 (Study CA209649); as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 21.2 of the RMP has also been submitted."}, {"id":"IAIN/0110","type":"IAIN","opinion":"2021-08-26","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2043","type":"WS","opinion":"2021-06-10","decision":"2021-07-28","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0095","type":"II","opinion":"2021-06-24","decision":"2021-07-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include adjuvant treatment of adult patients with oesophageal, or gastro-oesophageal junction cancer who have residual pathologic disease following prior neoadjuvant chemoradiotherapy for OPDIVO (study CA209577) as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 22.0 of the RMP has also been submitted."}, {"id":"WS/1840","type":"WS","opinion":"2021-05-20","decision":"2021-06-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the combination of nivolumab with ipilimumab in the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability_high (MSI-H) metastatic colorectal cancer (CRC) after prior fluoropyrimidine based combination chemotherapy; as a consequence, sections 4.1, 4.2 ,4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 20.2 for Opdivo and version 30.2 for Yervoy of the RMP have also been submitted."}, {"id":"WS/1881","type":"WS","opinion":"2021-04-22","decision":"2021-06-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM) for combination treatment of Opdivo and Yervoy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 (for both products) and 6.6 (for Opdivo) of the SmPC are updated. The Package Leaflet is updated in accordance. Version 20.1 for Opdivo and version 30.1 for Yervoy of the RMP has also been adopted."}, {"id":"II/0098","type":"II","opinion":"2021-03-11","decision":"2021-06-01","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 5.1 of the SmPC in order to update overall survival information based on the final OS data for study CA209238, listed as an obligation in the Annex II and in the RMP; study CA 209238 is a Phase 3, randomised double-blind study of OPDIVO versus Yervoy in patients who have undergone complete resection of Stage IIIb/c or Stage IV melanoma; the MAH took also the occasion to update section 4.8 of the SmPC to pull the safety data sets of nivolumab as monotherapy across advanced metastatic and adjuvant settings. The Package Leaflet is updated accordingly. The RMP version 17.2 has also been submitted."}, {"id":"PSUSA/00010379/202007","type":"PSUSA","opinion":"2021-02-25","decision":"2021-04-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"II/0092","type":"II","opinion":"2021-02-25","decision":"2021-04-13","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include in combination with cabozantinib for the first line treatment of advanced renal cell carcinoma for Opdivo; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 19.1 of the RMP has also been submitted."}, {"id":"IA/0099","type":"IA","opinion":"2021-02-12","decision":"2021-04-13","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0080","type":"II","opinion":"2020-10-15","decision":"2020-11-20","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) after prior fluoropyrimidine- and platinum-based chemotherapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 16.2 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives for Sweden and Denmark in the Package Leaflet."}, {"id":"WS/1790","type":"WS","opinion":"2020-07-23","decision":"2020-11-05","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to include at least 5 years (60 months) of follow-up for all subjects from study CA209067. Updated efficacy data provided in this submission include overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)."}, {"id":"WS/1783","type":"WS","opinion":"2020-09-17","decision":"2020-11-05","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include first-line treatment of metastatic non-small cell lung cancer in adults whose tumours have no sensitising EGFR mutation or ALK translocation for combination of OPDIVO/Yervoy and chemotherapy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 17.1 of the RMP for OPDIVO and version 28.1 for Yervoy have also been submitted."}, {"id":"IB/0085","type":"IB","opinion":"2020-07-14","decision":"2020-11-05","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IAIN/0084","type":"IAIN","opinion":"2020-05-13","decision":"2020-11-05","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0083","type":"IAIN","opinion":"2020-04-20","decision":"2020-11-05","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"R/0074","type":"R","opinion":"2020-02-27","decision":"2020-04-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0076/G","type":"II","opinion":"2020-01-23","decision":"2020-04-23","affects":["Annex II"],"codes":["B.I.a.1.a","B.I.a.1.e","B.I.a.1.f"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated with the inclusion of the following new active substance manufacturer: Swords Laboratories t/a Bristol-Myers Squibb Cruiserath Biologics, Cruiserath Road, Mulhuddart, Dublin"}, {"id":"IB/0079","type":"IB","opinion":"2019-12-20","decision":"2020-04-23","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"WS/1714","type":"WS","opinion":"2019-12-12","decision":"2020-01-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to update the safety information on myocarditis management for nivolumab monotherapy or for nivolumab in combination with ipilimumab therapy."}, {"id":"II/0073","type":"II","opinion":"2019-10-24","decision":"2020-01-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update sections 4.8 and 5.1 of the SmPC based on the final results from two studies: CA209017 (Open-label Randomized Phase III Trial comparing Nivolumab Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer) and CA209057 (Open-label Randomized Phase III Trial comparing Nivolumab Versus Docetaxel in Previously Treated Metastatic Non-Squamous Non-small Cell Lung Cancer)."}, {"id":"II/0069","type":"II","opinion":"2019-09-19","decision":"2019-10-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","6.6"],"scope":"Update of section 4.2, 5.1 and 6.6 of the SmPC in order to replace the current weight-based dosing regimen for the adjuvant treatment of melanoma by the flat dose regimens of 240 mg every 2 weeks (Q2W) administered intravenously (IV) over 30 minutes or 480 mg every 4 weeks (Q4W) administered IV over 60 minutes based on population pharmacokinetic data and an exposure-response efficacy analysis. The Package leaflet has been updated accordingly."}, {"id":"PSUSA/00010379/201901","type":"PSUSA","opinion":"2019-07-25","decision":"2019-09-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"IAIN/0068","type":"IAIN","opinion":"2019-06-07","decision":"2019-09-26","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0060/G","type":"II","opinion":"2019-04-26","decision":"2019-05-27","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC in order to include information from studies CA209171 (A Phase 2, single-arm, open-label, multicentre clinical trial with nivolumab monotherapy in subjects with advanced or metastatic squamous (Sq) cell non-small cell lung cancer (NSCLC) who have received at least one prior systemic regimen for the treatment of Stage IIIb/IV Sq NSCLC) and CA209172 (A Phase 2, single-arm, open-label, multicentre clinical trial with nivolumab monotherapy in subjects with histologically confirmed Stage III (unresectable) or Stage IV melanoma progressing after prior treatment containing an anti-CTLA-4 monoclonal antibody)."}, {"id":"IG/1059","type":"IG","opinion":"2019-02-15","decision":"2019-04-02","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUSA/00010379/201807","type":"PSUSA","opinion":"2019-01-31","decision":"2019-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"II/0057","type":"II","opinion":"2018-12-13","decision":"2019-03-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include descriptive efficacy data available from study CA209374 (A Phase 3b/4 Safety Trial of Nivolumab (BMS-936558) in Subjects With Advanced or Metastatic Renal Cell Carcinoma)."}, {"id":"WS/1278","type":"WS","opinion":"2018-11-15","decision":"2019-01-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the combination treatment with nivolumab and ipilimumab of adult patients with intermediate/poor-risk advanced renal cell carcinoma. As a consequence sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the Opdivo and Yervoy SmPCs were proposed to be updated. The Package Leaflet and the Risk Management Plan (version 19.0 for Yervoy and version 13.0 for Opdivo) were proposed to be updated in accordance. In addition, the Worksharing applicant (WSA) would take the opportunity to correct some typos throughout the Yervoy and Opdivo product information."}, {"id":"PSUSA/00010379/201801","type":"PSUSA","opinion":"2018-07-26","decision":"2018-09-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"II/0051/G","type":"II","opinion":"2018-05-17","decision":"2018-07-30","affects":["SmPC","Labelling","PL"],"codes":["A.7","B.II.b.5.b","B.II.d.1.c","B.II.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Sections 2, 6.3, 6.5 and 8 of the SmPC are being updated to reflect the addition of a new presentation: one vial of 24 mL containing 240 mg of nivolumab concentrate for solution for infusion. Annex A, Labelling and Package Leaflet (PL) are updated accordingly."}, {"id":"II/0047","type":"II","opinion":"2018-04-26","decision":"2018-07-30","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a warning on the nivolumab use in patients who have previously undergone allogeneic HSCT and the increased risk of rapid onset and severe Graft versus Host Disease (GVHD) based on evidence from spontaneous case reports, literature case reports, and from 2 multicenter case series. Annex II.D and the Package Leaflet are updated accordingly. The RMP version 10.2 has also been submitted to include the “risk of GVHD with nivolumab after allogeneic HSCT” as an “Important Potential Risk” based on the RMP template (Revision 2)."}, {"id":"II/0041","type":"II","opinion":"2018-06-28","decision":"2018-07-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include adjuvant treatment of adults with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated in order to add efficacy and safety information from the pivotal Study CA209238. The Package Leaflet is updated in accordance. In addition, the already authorised indication in squamous cell cancer of the head and neck has been further clarified. Furthermore, the Marketing authorisation holder (MAH) took the opportunity to make minor editorial changes to the PI. Annex II has been updated to reflect new conditions."}, {"id":"II/0036/G","type":"II","opinion":"2018-03-22","decision":"2018-04-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2","6.6"],"scope":"Update of sections 4.2, 5.1, 5.2 and 6.6 of the SmPC in order to introduce new dosing regimens (240 mg every 2 weeks and 480 mg every 4 weeks) and infusion time (30-minutes) depending on the dose: - The 240 mg every 2 weeks regimen in combination with the 30-minute infusion time is recommended for currently approved indications (melanoma, renal cell carcinoma, non-small lung cancer, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, urothelial carcinoma). - The 480 mg every 4 weeks regimen in combination with the 60-minute infusion time is recommended for melanoma and renal cell carcinoma indications."}, {"id":"IB/0048","type":"IB","opinion":"2018-02-21","decision":"2018-04-23","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00010379/201707","type":"PSUSA","opinion":"2018-01-25","decision":"2018-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"II/0038","type":"II","opinion":"2017-11-09","decision":"2018-03-23","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC with longer follow-up for subjects proceeding to allogeneic transplant following nivolumab treatment, of section 5.1 of the SmPC with efficacy data from longer follow-up based on final results from study CA209205 listed as a PAES in the Annex II; this is a Phase 2, non-comparative, multi-cohort, single-arm, open-label study of nivolumab (BMS-936558) in cHL subjects after failure of ASCT. Annex II is updated accordingly. Version 7.7 of the RMP has been submitted."}, {"id":"IB/0046","type":"IB","opinion":"2018-01-12","decision":"2018-03-23","affects":["SmPC","PL"],"codes":["B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IB/0045/G","type":"IB","opinion":"2017-12-22","decision":"2018-03-23","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0032","type":"II","opinion":"2017-09-14","decision":"2017-10-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Update of sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC in order to update the statement on outcome benefit, to add administration guidance, to update the safety information and updated overall survival data based on final results from study CA209067 (listed as an imposed PAES in the Annex II). Study CA209067 is an interventional, randomized, double-blind study of nivolumab monotherapy or nivolumab combined with ipilimumab versus ipilimumab monotherapy in adult subjects with previously untreated, unresectable or metastatic Stage III or Stage IV melanoma. The Package Leaflet is updated accordingly. The RMP version 7.6 has also been submitted."}, {"id":"PSUSA/00010379/201701","type":"PSUSA","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab"}, {"id":"IB/0035/G","type":"IB","opinion":"2017-05-16","decision":"2017-09-18","affects":["SmPC","PL"],"codes":["C.I.z","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0031/G","type":"II","opinion":"2017-03-30","decision":"2017-06-02","affects":["Annex II","PL"],"codes":["B.II.b.2.b","B.II.b.2.c.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place for a biol/immunol product and any of the test methods at the site is a biol/immunol method; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing for a biol/immunol product and any of the test methods is a biol/immunol/immunochemical method"}, {"id":"II/0024","type":"II","opinion":"2017-04-21","decision":"2017-06-02","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Duration of response with longer follow-up, following completion of PAES CA209037 (Randomized, Open-Label, Phase 3 Trial of nivolumab vs Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy) and its addendum on predictability of efficacy with biomarkers. This application fulfils ANX 001 and 003.1. Annex II has been updated accordingly. RMP version 5.5 has been submitted within this application."}, {"id":"II/0019","type":"II","opinion":"2017-04-21","decision":"2017-06-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include the treatment of locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum-containing therapy for OPDIVO. As a consequence, sections 4.1, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated in order to add the proposed indication, add a warning about the patient populations excluded from the clinical trial, and update the safety information. The Package Leaflet is updated in accordance. Moreover, the updated RMP version 7.2 has been submitted"}, {"id":"II/0023","type":"II","opinion":"2017-02-23","decision":"2017-04-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the safety and pharmacological information with the 24 months data from the completed NSCLC studies CA209017 and CA209057."}, {"id":"II/0017","type":"II","opinion":"2017-03-23","decision":"2017-04-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy for OPDIVO as monotherapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, of the SmPC are updated in order to add the proposed new indication, add a warning to recommend careful consideration before initiating treatment with nivolumab in patients excluded from the SCCHN clinical trial (patients with a baseline performance score ≥ 2, untreated brain metastasis, active autoimmune disease, medical conditions requiring systemic immunosuppression, or carcinoma of the nasopharynx or salivary gland as the primary tumour sites) and update…"}, {"id":"IB/0028","type":"IB","opinion":"2016-12-20","decision":"2017-03-24","affects":["SmPC","PL"],"codes":["B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"II/0018","type":"II","opinion":"2016-12-15","decision":"2017-01-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to update the safety information for toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), myositis, myocarditis and rhabdomyolysis based on findings from routine pharmacovigilance activities. The Package Leaflet is updated accordingly. In addition, the RMP is updated to version 5.6 to reflect this new safety information."}, {"id":"II/0014","type":"II","opinion":"2016-07-28","decision":"2016-11-21","affects":["Annex II"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product"}, {"id":"II/0012","type":"II","opinion":"2016-10-13","decision":"2016-11-21","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"II/0011/G","type":"II","opinion":"2016-07-14","decision":"2016-11-21","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.a.4.a","B.I.a.4.z","B.I.b.2.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change to in-process tests or limits applied during the manufacture of the AS - Tightening of in-process limits; Change to in-process tests or limits applied during the manufacture of the AS - Other variation; Change in test procedure for AS or starting material/reagent/intermediate - Other changes to a test procedure (including replacement or addition) for the AS or a starting material/intermediate"}, {"id":"IB/0016","type":"IB","opinion":"2016-06-20","decision":"2016-11-21","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0003","type":"II","opinion":"2016-04-01","decision":"2016-05-11","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include treatment in combination with ipilimumab of advanced (unresectable or metastatic) melanoma in adults based on interim data from study CA209067 and the final CSR of study CA209069. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC have been updated and the Package Leaflet has been revised accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC, Annex II and Package Leaflet, and to provide a paediatric non-clinical biomarker study as part of the application to fulfil paediatric requirements."}, {"id":"II/0008","type":"II","opinion":"2016-02-25","decision":"2016-04-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of Indication to add treatment as monotherapy of patients with advanced renal cell carcinoma (RCC) after prior therapy in adults, based on Study CA209025; a phase 3 study of nivolumab vs. everolimus in subjects with advanced or metastatic clear-cell RCC who have received prior anti-angiogenic therapy, and the CA209010 addendum study report; phase 2 dose-ranging study of nivolumab in subjects with progressive advanced/metastatic clear-cell RCC who have received prior anti-angiogenic therapy."}, {"id":"II/0004","type":"II","opinion":"2015-12-17","decision":"2016-04-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information with reference to the ADR toxic epidermal necrolysis (TEN). The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the contact details of the local representatives in the Package Leaflet. A revised RMP version 2.1 was agreed during the procedure."}, {"id":"II/0002","type":"II","opinion":"2016-02-25","decision":"2016-04-04","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include treatment as monotherapy of locally advanced or metastatic non-squamous NSCLC after prior chemotherapy in adults based on study CA209057. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC have been updated and the Package Leaflet has been updated accordingly. Further, SmPC section 4.8 has been revised with updated combined clinical trial exposure numbers to reflect inclusion of studies in non-squamous NSCLC and in nivolumab in combination with ipilimumab in advanced melanoma."}, {"id":"II/0001","type":"II","opinion":"2015-09-24","decision":"2015-10-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy in adults (in line with the Nivolumab BMS MAA, procedure EMEA/H/C/003840). As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC have been updated and the Package Leaflet has been revised accordingly. Further, Annex II has been updated to include a post-authorisation efficacy study as a new obligation in line with the agreed Annex II for Nivolumab BMS. In addition, the MAH took the opportunity to make editorial changes in the SmPC, Annex II, labelling and Package Leaflet. A revised RMP version 2.0 was agreed during the procedure."} ] }, "nogapendekin-alfa-inbakicept__anktiva": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/anktiva-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000351303","type":"IAIN","opinion":"2026-06-11","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"E.4 Change in the name and/or address of the marketing Term name: E.4 authorisation holder, ASMF holder, storage site of the master and/or working cell bank, manufacturing site for an active substance, intermediate or finished product, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier - E.4.a) The change in the name and/or address concerns the marketing authorisation holder"} ] }, "obecabtagene-autoleucel__aucatzyl": { "source": [], "procedures": [] }, "obinutuzumab__gazyvaro": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/gazyvaro-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/gazyvaro-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000313033","type":"II","opinion":"2026-01-29","decision":"2026-03-05","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to include the administration of obinutuzumab as a short duration infusion (SDI) in patients with lupus nephritis (LN)"}, {"id":"EMA/VR/0000257509","type":"II","opinion":"2025-05-22","decision":"2025-12-04","affects":["SmPC","PL"],"codes":["C.I.4","B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet due to new quality, preclinical, clinical or pharmacovigilance data; Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"EMA/VR/0000244907","type":"II","opinion":"2025-10-16","decision":"2025-12-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include treatment of adult patients with active lupus nephritis who are receiving standard therapy for GAZYVARO, based on results from study Regency (CA41705). This is an ongoing, Phase III, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of obinutuzumab administered at standard infusion rates in patients with ISN/RPS 2003 Class III or IV lupus nephritis treated with standard-of-care therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 11 of the RMP has also been submitted."}, {"id":"PSUSA/00010279/202310","type":"PSUSA","opinion":"2024-06-27","decision":"2024-09-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - obinutuzumab"}, {"id":"II/0053/G","type":"II","opinion":"2023-09-07","decision":"2024-09-06","affects":["Annex II"],"codes":["B.I.a.2.a","B.I.a.4.c","B.I.a.1.e","B.I.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Change to in-process tests or limits applied during the manufacture of the AS - Deletion of a non-significant in-process test; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in test procedure for AS or starting material/reagent/intermediate - Minor changes to an approved test procedure"}, {"id":"II/0054/G","type":"II","opinion":"2024-09-05","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Grouped application comprising two variations as follows:"}, {"id":"II/0051","type":"II","opinion":"2022-09-01","decision":"2023-05-05","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in line with the SmPC Guideline following the recommendation by PRAC in the outcome for the signal assessment of non-overt disseminated intravascular coagulation (DIC) (EPITT no: 19711). The Package Leaflet is updated accordingly."}, {"id":"II/0047","type":"II","opinion":"2022-07-21","decision":"2023-05-05","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study BO21223/GALLIUM listed as a category 3 study in the RMP. This is an open-label, international, multicenter, randomized, Phase III study to investigate the efficacy and safety of obinutuzumab administration at standard infusion rate plus chemotherapy followed by obinutuzumab maintenance therapy for responders (G-chemo arm) compared with rituximab plus chemotherapy followed by rituximab maintenance therapy for responders (R-chemo arm) in patients with previously untreated advanced indolent non-Hodgkin’s lymphoma (iNHL). The RMP version 9.0 has also been submitted."}, {"id":"IAIN/0049","type":"IAIN","opinion":"2022-05-06","decision":"2023-05-05","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0044/G","type":"II","opinion":"2021-09-16","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to include the administration of obinutuzumab as a short duration infusion (SDI) of approximately 90 minutes in patients with Follicular Lymphoma (FL), based on the end of induction safety and efficacy data from the ongoing Phase IV study MO40597 (GAZELLE); the Package Leaflet is updated accordingly. The RMP version 8.0 has also been submitted. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"IB/0042","type":"IB","opinion":"2021-01-08","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0036","type":"II","opinion":"2020-02-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC based on data from the final CSR of the pivotal study GA04753g/GO01297/GADOLIN to fulfill a Category 3 PAM (MEA 006). The PL and RMP are updated accordingly."}, {"id":"R/0031","type":"R","opinion":"2019-01-31","decision":"2019-04-02","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0030","type":"N","opinion":"2018-08-09","decision":"2019-04-02","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0023","type":"II","opinion":"2018-05-17","decision":"2019-04-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 and 5.1 of the SmPC in order to update the overall survival data based on final results from study BO21004/CLL11 listed as a category 3 study in the RMP; this is the pivotal study that evaluated the efficacy and safety of obinutuzumab as therapy for patients with previously untreated CLL with comorbidities; The RMP version 4.0 has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity format the listing of “other side effects” and correct the term heart attack to heart failure in section 4 of the Package Leaflet."}, {"id":"T/0024","type":"T","opinion":"2018-03-15","decision":"2018-04-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0020","type":"II","opinion":"2017-10-26","decision":"2018-04-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to revise the safety information on delayed hypersensitivity reactions based on a review of relevant cases by the Marketing authorisation holder (MAH). In addition, the MAH took the opportunity to introduce editorial changes to the SmPC and package leaflet."}, {"id":"II/0016","type":"II","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of Indication to include a new indication for Gazyvaro in combination with chemotherapy, followed by Gazyvaro maintenance therapy in patients achieving a response, for the treatment of patients with previously untreated advanced follicular lymphoma; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet and the RMP are updated in accordance. In addition, the due date for provision of the final clinical study report of study BO21223/GALLIUM listed in the Gazyvaro RMP as Category 3 has been updated. Furthermore, the Annex II is brought in line with the latest QRD template (version 10)."}, {"id":"II/0007","type":"II","opinion":"2016-04-28","decision":"2016-06-13","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","5.1","5.2","5.3","6.6"],"scope":"Extension of indication to add the treatment of patients with follicular lymphoma based on the results of the pivotal study GAO4753g. As a consequence, sections 4.1, 4.2, 4.5, 4.8, 5.1 and 5.2 of the SmPC have been updated. The Package Leaflet has been updated accordingly. Furthermore, the MAH took the opportunity to make editorial changes to sections 4.4, 4.6, 5.3 and 6.6 of the SmPC."}, {"id":"II/0009","type":"II","opinion":"2016-04-01","decision":"2016-05-20","affects":["Annex II","Labelling"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0003","type":"II","opinion":"2015-05-21","decision":"2016-05-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of the SmPC sections 4.2 and 4.4 to revise the wording related to tumour lysis syndrome (TLS) in order to emphasize the importance of pre-medication and careful monitoring of patients at risk of TLS. In addition, text relating to batch number has been included in section 4.4 of the SmPC to improve the traceability of biological medicinal products. The Package Leaflet is updated accordingly."} ] }, "odronextamab__ordspono": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ordspono-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ordspono-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000347570","type":"II","opinion":"2026-07-23","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add 'Tumour Flare' to the list of adverse drug reactions (ADRs) with frequency 'common' based on post-marketing data and literature. The Package Leaflet is updated accordingly, In addition, the MAH took the opportunity to implement editorial changes to the PI."}, {"id":"EMA/R/0000254850","type":"R","opinion":"2025-05-22","decision":"2025-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation."} ] }, "olaparib__lynparza": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lynparza-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lynparza-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000296305","type":"IB","opinion":"2026-02-12","decision":null,"affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To extend the due date for the phase III PAES study D9311C00001 (DUO-E) from December 2026 to November 2028 in the RMP and Annex II of the SmPC. In addition, the MAH has taken this opportunity to correct an error identified for the DUO-E study involving a raw data mapping issue that affected the COVID-19 study disruption data and impacts the COVID-19 tables in the CSR. As there is no change in the interpretation or the overall conclusion this has exceptionally been included as part of this type IB."}, {"id":"EMA/VR/0000287658","type":"II","opinion":"2025-10-09","decision":"2025-12-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to add paediatric information based on final results from study D0816C00025, a PIP study and submitted in accordance with Article 46 of Regulation (EC) No 1901/2006. This is a Phase I, Open-label, Parallel Group Study to Investigate Olaparib Safety and Tolerability, Efficacy and Pharmacokinetics in Paediatric Patients with Solid Tumours. In addition, the MAH is taking the opportunity to correct errors in CSR Addendum 1 for Lynparza study D081CC00006 (OlympiA)."}, {"id":"EMA/VR/0000252324","type":"II","opinion":"2025-06-05","decision":"2025-12-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to include the results of a descriptive analysis of Overall Survival at five years last subject randomised from study D081CC00006 (OlympiA); a randomised, double-blind, parallel group, placebo-controlled multi-centre phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with Germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy."}, {"id":"EMA/VR/0000246964","type":"II","opinion":"2025-05-15","decision":"2025-12-15","affects":["SmPC","PL"],"codes":["C.I.4","A.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"A grouped application comprising of a Type II variation and a Type I variation, as follows: Type II (C.I.4): Update of sections 4.4 and 4.8 of the SmPC in order to update the warning on ‘Pneumonitis’ and add it to the list of adverse drug reactions (ADRs)"}, {"id":"IA/0071","type":"IA","opinion":"2024-12-17","decision":null,"affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"WS/2463","type":"WS","opinion":"2024-06-27","decision":"2024-08-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to include paediatric information based on final results from study D419EC00001 “Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or Durvalumab in Combination with Tremelimumab in Pediatric Patients with Advanced Solid Tumors and Hematological Malignancies”. In addition, the MAH took this opportunity to introduce editorial changes."}, {"id":"II/0064","type":"II","opinion":"2023-08-31","decision":"2024-01-25","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC to update safety and efficacy results including a descriptive analysis of overall survival (OS) at seven years after the last patient was randomised in study D0818C0001 (SOLO1). This is a Phase III randomised, double blind, placebo controlled, multicentre study in which advanced ovarian cancer patients with BRCA mutations who had responded following first-line platinum-based chemotherapy were randomised 2:1 to receive either Olaparib (300 mg bd, tablet formulation) or placebo. The RMP version 28.1 is approved. In addition, the MAH took the opportunity to update section D of Annex II."}, {"id":"II/0061","type":"II","opinion":"2023-10-05","decision":"2024-01-25","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the overall survival and safety information, based on the final results from study D081SC00001 (PROpel), listed as a PAES in the Annex II; this is a randomised, double-blind, placebo-controlled, multicentre phase III study of olaparib plus abiraterone relative to placebo plus abiraterone as first-line therapy in men with metastatic castration resistant prostate cancer; the Annex II is updated in accordance. The RMP version 27.1 is approved. In addition, the MAH took the opportunity to revise the list of local representatives in the package leaflet"}, {"id":"II/0058","type":"II","opinion":"2023-01-12","decision":"2024-01-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the olaparib tablet SmPC based on results from study D0816C00020 (OPINION); this is a Phase IIIb single arm, multicentre study, investigating olaparib as a maintenance treatment in patients with platinum sensitive relapsed ovarian, fallopian tube or primary peritoneal cancer following 2 or more lines of platinum-based chemotherapy and who did not have a known deleterious or suspected deleterious gBRCA mutation. The MAH also took the opportunity to make minor editorial corrections to the product information."}, {"id":"II/0057","type":"II","opinion":"2023-03-30","decision":"2024-01-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the long-term safety data and the final OS analysis from PAOLA-1 study (D0817C00003). This is a Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB – IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer Treated with Standard First Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make minor changes to the SmPC for clarity."}, {"id":"IAIN/0065","type":"IAIN","opinion":"2023-09-15","decision":"2024-01-25","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0063/G","type":"IAIN","opinion":"2023-06-02","decision":"2024-01-25","affects":["Annex II","PL"],"codes":["B.II.b.2.a","A.5.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0053","type":"II","opinion":"2022-11-10","decision":"2022-12-16","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the use of Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated. Consequently, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC and Annex II are updated. The Package Leaflet is updated accordingly. The RMP version 26.1 has also been submitted."}, {"id":"IB/0056/G","type":"IB","opinion":"2022-09-01","decision":"2022-12-16","affects":["SmPC","Labelling","PL"],"codes":["C.I.11.z","C.I.7.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation; Deletion of - a pharmaceutical form"}, {"id":"II/0051/G","type":"II","opinion":"2022-06-23","decision":"2022-08-02","affects":["SmPC","PL"],"codes":["C.I.6.a","B.I.z"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","5.1"],"scope":"Extension of indication to include the use of Lynparza tablets as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 5.1 of the SmPC are updated. The SmPC of Lynparza capsule has been revised accordingly to reflect updated safety information. The Package Leaflet is updated in accordance. In addition, the list of local representatives in the PL has been revised."}, {"id":"II/0048","type":"II","opinion":"2021-11-11","decision":"2022-03-24","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the olaparib tablet SmPC based on results from study D0816C00020 (OPINION) listed as a PAES in the Annex II; this is a Phase IIIb single arm, multicentre study, investigating olaparib as a maintenance treatment in patients with platinum-sensitive relapsed ovarian, fallopian tube or primary peritoneal cancer following 2 or more lines of platinum based chemotherapy and who did not have a known deleterious or suspected deleterious gBRCA mutation; the Annex II is updated accordingly. The RMP version 22.1 has also been submitted."}, {"id":"II/0047","type":"II","opinion":"2021-09-02","decision":"2022-03-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update safety and efficacy information based on the final analysis of overall survival and safety update from study POLO, a Phase III, randomised, double-blind, placebo-controlled, multicentre study in gBRCAm patients with metastatic pancreatic adenocarcinoma whose disease had not progressed after receiving first-line platinum-based chemotherapy."}, {"id":"II/0045","type":"II","opinion":"2021-05-06","decision":"2022-03-24","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC of Lynparza capsules based on the final report from Study/D0816C00012 (ORZORA) listed as PAES in the Annex II of the Product Information. This is an Open Label, Single Arm, Multi-centre Study to Assess the Clinical Effectiveness and Safety of Lynparza (Olaparib) Capsules Maintenance Monotherapy in Platinum Sensitive Relapsed somatic or germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy. The Annex II is updated accordingly."}, {"id":"II/0044","type":"II","opinion":"2021-05-06","decision":"2022-03-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC of Lynparza tablets based on updated efficacy and safety data from the Phase III PAOLA-1 study. In addition, the MAH took the opportunity to switch the order of the capsule and tablet formulations in Annex I of the PI."}, {"id":"II/0042","type":"II","opinion":"2021-02-11","decision":"2022-03-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to add Myelodysplastic syndrome (MDS)/Acute myeloid leukaemia (AML) to the list of adverse drug reactions with the frequency uncommon, modify the existing warning on MDS/AML and update efficacy information based on final results from study SOLO-2 listed as a PAES in the Annex II; this is a phase III randomised, double blind, placebo controlled, multicentre study of olaparib maintenance monotherapy in platinum sensitive relapsed BRCA mutated ovarian cancer patients who are in complete or partial response following platinum based chemotherapy; the Package Leaflet and Annex II are updated accordingly."}, {"id":"IA/0052","type":"IA","opinion":"2021-11-22","decision":"2022-03-24","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0036","type":"II","opinion":"2020-09-17","decision":"2020-11-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the use of Lynparza tablets as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 of the SmPC are updated. The PL is updated accordingly. In addition, sections 4.2, 4.4 and 4.8 of the SmPC for Lynparza hard capsules are revised based on updated safety data analysis and minor changes are made to section 5.3. The RMP version 20.3 has also been accepted."}, {"id":"II/0035","type":"II","opinion":"2020-09-17","decision":"2020-11-03","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the use of Lynparza tablets in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 of the SmPC are updated. The PL is updated accordingly."}, {"id":"PSUSA/00010322/201912","type":"PSUSA","opinion":"2020-07-23","decision":"2020-09-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - olaparib"}, {"id":"II/0033","type":"II","opinion":"2020-05-28","decision":"2020-07-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of Indication to support the use of Lynparza tablets (100mg and 150 mg) for the maintenance treatment of gBRCAm metastatic pancreatic cancer based on the results from the pivotal Phase 3 study, POLO; as a consequence, sections 4.1, 4.2, 4.8, 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update section 4.8 for lynparza hard capsules (50 mg) to revise list of ADR based on the pooled safety data analysis. The RMP version 18.3 has also been submitted. Furthermore, the PI is brought in line with the latest guideline regarding the sodium content."}, {"id":"IB/0039","type":"IB","opinion":"2020-04-22","decision":"2020-07-03","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"R/0029","type":"R","opinion":"2019-07-25","decision":"2019-10-01","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0028","type":"II","opinion":"2019-05-16","decision":"2019-10-01","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to include information on the in vitro effect of olaparib on UGT enzymes based on results from in vitro assays. In addition, the MAH is proposing to change the due date for submission of the final CSR of the phase IV, open label, single arm study (D0816C00012/ORZORA) in patients with relapsed platinum sensitive ovarian cancer who are in response following platinum-based chemotherapy and who carry loss of function germline or somatic BRCA mutations, listed as a PAES in the Annex II."}, {"id":"IB/0032","type":"IB","opinion":"2019-05-03","decision":"2019-10-01","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0023","type":"II","opinion":"2019-04-26","decision":"2019-06-12","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the use of Lynparza (tablet formulation) as monotherapy for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy. As a consequence of this new indication, sections 4.1, 4.2, 4.4, 4.8 and 5.1 the SmPC of the tablet formulation have been updated. Sections 4.2, 4.4, 4.8 and 5.1 of the SmPC of the capsule formulation have also been modified to reflect information that is also relevant to the capsule formulation."}, {"id":"IAIN/0031","type":"IAIN","opinion":"2019-04-05","decision":"2019-06-12","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0030/G","type":"IAIN","opinion":"2019-04-05","decision":"2019-06-12","affects":["Annex II","PL"],"codes":["B.II.b.2.a","B.II.b.2.c.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing"}, {"id":"II/0022","type":"II","opinion":"2018-07-26","decision":"2019-04-08","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"The instructions on how to store Lynparza have been updated to recommend storage in a refrigerator (2°C – 8°C). If preferred, Lynparza capsules can be kept out of the refrigerator (below 30°C) for up to 3 months. After this period, any capsules that have not been used must be thrown away. Lynparza should not be frozen. The shelf-life has also been extended from 18 months to 2 years."}, {"id":"II/0020","type":"II","opinion":"2019-02-28","decision":"2019-04-08","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","5.1","5.2"],"scope":"Extension of indication to include the use of Lynparza tablets as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2-negative locally advanced or metastatic breast cancer; patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments. Patient with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy."}, {"id":"X/0016/G","type":"X","opinion":"2018-02-22","decision":"2018-05-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data; Annex I_2.(a) Change of bioavailability; Annex I_2.(b) Change of pharmacokinetics change in rate of release; Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"PSUSA/00010322/201612","type":"PSUSA","opinion":"2017-07-20","decision":"2017-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - olaparib"}, {"id":"IB/0017/G","type":"IB","opinion":"2017-06-12","decision":"2017-09-18","affects":["SmPC"],"codes":["B.II.d.1.g","B.II.f.1.a.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Addition or replacement (excluding biological or immunological product) of a specification parameter wit its corresponding test method as a result of a safety or quality issue; Stability of FP - Reduction of the shelf life of the finished product - As packaged for sale; Stability of FP - Change to an approved stability protocol"}, {"id":"II/0009/G","type":"II","opinion":"2016-11-10","decision":"2016-12-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0008/G","type":"II","opinion":"2016-09-15","decision":"2016-10-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of section 4.2 and 5.2 of the SmPC with recommendations for patients with renal impairment based on the results of study D0816C00006 (MEA 006), that evaluated the influence of mild and moderate renal impairment on the pharmacokinetics of Olaparib. The Package Leaflet and RMP were updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update local representatives in the PL, to bring the PI in line with the latest QRD template version and introduce minor corrections in the PI."}, {"id":"II/0001/G","type":"II","opinion":"2016-02-25","decision":"2016-03-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.11.z","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.6","5.1","5.2"],"scope":"Update of sections 4.2, 4.4, 4.5, 4.6 and 5.2 of the SmPC in order to include further information related to pharmacokinetic interactions based on the in vivo interaction study D0816C00008, 3 in vitro interaction studies (ADME-AZS-Wave3-140714, ADME-AZS-Wave3-140725 and 140483) and data from previously submitted interaction studies. The provision of the final CSR for study D0816C00008 addresses the post-authorisation measure MEA 004. Further, the MAH provided the study report for in vitro study 8305083 as part of the application."} ] }, "osimertinib__tagrisso": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tagrisso-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tagrisso-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000340013","type":"II","opinion":"2026-07-09","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on skeletal muscle toxicity based on post-marketing experience and literature. The Package Leaflet is updated accordingly. The RMP version 18.1 has also been agreed."}, {"id":"EMA/VR/0000326185","type":"II","opinion":"2026-05-21","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"A grouped application comprised of two Type II variations, as follows: Update of section 5.1 of the SmPC in order to update clinical information, based on the final overall survival (OS) analysis from study D5169C00001 (FLAURA2). This is a Phase III, open-label, randomised study of osimertinib with or without platinum plus pemetrexed chemotherapy, as first-line treatment in patients with epidermal growth factor receptor mutation positive, locally advanced or metastatic non-small cell lung cancer. Update of section 4.8 of the SmPC in order to include eosinophilic pneumonia as an adverse drug reaction following the review of the MAH internal safety data."}, {"id":"EMA/VR/0000310732","type":"IAIN","opinion":"2025-12-03","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of product Characteristics, Labelling or Package Leaflet intended to implement the outcome of a PRAC signal recommendation: implementation of wording agreed by the competent authority that do not require any further assessment"}, {"id":"II/0056","type":"II","opinion":"2024-11-14","decision":"2024-12-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of adult patients with locally advanced, unresectable NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy for TAGRISSO as monotherapy, based on results from study D5160C00048 (LAURA); this is a Phase III, randomised, double-blind, placebo-controlled, multicenter international study of osimertinib as maintenance therapy in patients with locally advanced unresectable EGFR mutation-positive non-small cell lung cancer (stage III) whose disease has not progressed following definitive platinum-based chemoradiation…"}, {"id":"II/0054","type":"II","opinion":"2024-02-08","decision":"2024-06-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add ‘Skin Hyperpigmentation’ to the list of adverse drug reactions (ADRs) with frequency ‘uncommon’ based on literature. The Package leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet"}, {"id":"II/0053","type":"II","opinion":"2024-05-30","decision":"2024-06-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include TAGRISSO in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations, based on final results from study FLAURA2 (D5169C00001); this is a Phase III, open-label, randomized study of osimertinib with or without platinum plus pemetrexed chemotherapy, multicentre study to assess the efficacy and safety of TAGRISSO as first-line treatment in patients with EGFR mutation-positive, locally advanced or metastatic NSCLC."}, {"id":"II/0052","type":"II","opinion":"2023-09-28","decision":"2024-06-28","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information (final OS data) based on final results from study D5164C00001 (ADAURA) listed as a PAES in the Annex II; this is a Phase III, double-blind, randomised, placebo-controlled study, designed to assess the efficacy and safety of osimertinib versus placebo in the adjuvant setting in patients with stage IB-IIIA epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC) who have undergone complete tumour resection, with or without postoperative adjuvant chemotherapy. Annex II has also been updated accordingly to remove this study. The RMP version 15.2 is approved."}, {"id":"II/0050","type":"II","opinion":"2023-06-22","decision":"2023-07-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to add toxic epidermal necrolysis (TEN) as a new adverse drug reactions (ADRs) with frequency uncommon and to include corresponding warning and related dose modification in the posology section, and to update the frequency of interstitial lung disease (ILD) based on an internal safety information review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0047","type":"II","opinion":"2022-10-06","decision":"2023-07-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on final results from studies ODIN-BM and ODIN-HV; these are two phase I clinical pharmacology studies conducted in EGFRm+ NSCLC patients (ODIN-BM) and healthy volunteers (ODIN-HV) to determine osimertinib blood-brain barrier (BBB) penetration and brain distribution in patients with brain metastases and healthy volunteers with an intact BBB, respectively."}, {"id":"PSUSA/00010472/202111","type":"PSUSA","opinion":"2022-07-21","decision":"2022-09-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - osimertinib"}, {"id":"R/0044","type":"R","opinion":"2022-01-27","decision":"2022-03-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0045","type":"II","opinion":"2022-01-27","decision":"2022-03-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to reflect the outcome of the 104 Week Oral (Gavage) Carcinogenicity Study (507363) in the Rat submitted as recommended by the CHMP."}, {"id":"II/0039/G","type":"II","opinion":"2021-04-22","decision":"2021-05-21","affects":["SmPC","PL"],"codes":["B.I.b.1.e","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3"],"scope":"Extension of indication of Tagrisso to include the adjuvant treatment after complete tumour resection in EGFR mutant non-small cell lung cancer (NSCLC) patients, based on the results from the pivotal Phase 3 randomised, placebo-controlled study ADAURA (D5164C00001); as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated accordingly. Version 14.3 of the RMP has also been agreed."}, {"id":"II/0037","type":"II","opinion":"2020-09-03","decision":"2021-03-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0036","type":"II","opinion":"2020-06-25","decision":"2021-03-09","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the information regarding overall survival (OS) based on the final results from study D5160C00003 (AURA3); this is a randomized study of osimertinib versus platinum-based doublet chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with previous EGFR TKI. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.1."}, {"id":"II/0033","type":"II","opinion":"2020-03-12","decision":"2021-03-09","affects":["SmPC","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0032","type":"II","opinion":"2020-04-02","decision":"2021-03-09","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include erythema multiforme as an adverse drug reaction following the review of the MAH internal safety data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity of this procedure to add the event frequency of Stevens-Johnson syndrome to align with the approved text in the SmPC."}, {"id":"II/0031","type":"II","opinion":"2019-09-19","decision":"2019-10-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to include onychalgia in the list of associated clustered terms for paronychia further to a MAH internal safety information review. The Package leaflet has been updated accordingly."}, {"id":"II/0029","type":"II","opinion":"2019-09-19","decision":"2019-10-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to reflect the outcome of study D5160C00035, an open-label, Phase I study to assess the pharmacokinetics, safety and tolerability of osimertinib following a single oral 80 mg dose to patients with advanced solid tumours and normal renal function or severe renal impairment. This study was a Category 3 study in the EU-RMP. The RMP version 13 has also been submitted."}, {"id":"PSUSA/00010472/201811","type":"PSUSA","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - osimertinib"}, {"id":"II/0024","type":"II","opinion":"2018-07-19","decision":"2018-08-31","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC based on the results from Study D5160C00008, undertaken to determine the pharmacokinetics, safety and tolerability of AZD9291 following a single oral dose to patients with advanced solid tumours and normal hepatic function or mild or moderate hepatic impairment. An updated RMP version 11 was agreed during the procedure."}, {"id":"II/0021","type":"II","opinion":"2018-06-14","decision":"2018-08-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of SmPC sections 4.5 and 5.2 to reflect the results of Study D5160C00036, undertaken to assess the effect of single and multiple oral doses of osimertinib on the pharmacokinetics of a P-glycoprotein probe drug (Fexofenadine) in patients with advanced EGFRm NSCLC that have progressed on a prior EGFR-TKI regimen. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make a correction in Annex II and to implement minor editorial and/or QRD-template related changes in the SmPC and Package Leaflet. A revised RMP version 9 was provided as part of the application."}, {"id":"II/0019","type":"II","opinion":"2018-04-26","decision":"2018-06-07","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include (as monotherapy) first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations, based on data from the FLAURA study (D5160C00007); a phase III, double-blind, randomised study to assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor-Tyrosine Kinase Inhibitor as first-line treatment in patients with epidermal growth factor receptor mutation-positive, locally-advanced or metastatic non-small-cell lung cancer."}, {"id":"II/0015","type":"II","opinion":"2017-07-06","decision":"2018-06-07","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC to include data from studies performed to investigate human plasma protein binding (Study No. BS001265-53-AZD9291), the assessment of non-specific incubational binding in transporter inhibition assays (Study No. BS000760-92) and the implications on transporter DDI risk assessment. In addition, the MAH took the opportunity to implement minor updates and editorial changes in the SmPC and to update the address of the MAH and manufacturer in SmPC section 7, the labelling and the Package Leaflet."}, {"id":"II/0014/G","type":"II","opinion":"2017-07-06","decision":"2018-06-07","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC to include information regarding CNS distribution based on non-clinical data."}, {"id":"II/0009/G","type":"II","opinion":"2017-02-23","decision":"2017-04-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Update of SmPC sections 4.2, 4.4, 4.8, 5.1 and 5.2 based on the results from study D5160C00003 (AURA3) and the updated CSRs for studies D5160C00001 (AURAex) and D5160C00002 (AURA2). The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make editorial changes in the SmPC and Package Leaflet. The provision of the CSR from study AURA3 addressed the remaining Specific Obligation for Tagrisso and hence it is recommended to convert the Marketing Authorisation from a Conditional Marketing Authorisation to a Marketing Authorisation not subject to Specific Obligations. Annex II has been updated in accordance."}, {"id":"II/0004","type":"II","opinion":"2017-01-26","decision":"2017-03-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2","6.5"],"scope":"Update of section 5.2 of the SmPC in view of the results of study 20 which was performed to assess the absolute bioavailability and to evaluate the PK parameters of Tagrisso in plasma following a single oral dose and a radio-labelled intravenous (IV) microdoseof[14C] Tagrisso in healthy male subjects. In addition, the MAH took the opportunity to make a minor correction in SmPC section 6.5 and the Package Leaflet, where blister strips have been amended to blisters. Further, an updated RMP version 5.0 was agreed during the procedure."}, {"id":"IB/0011","type":"IB","opinion":"2016-11-17","decision":"2017-03-22","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"II/0003","type":"II","opinion":"2016-09-15","decision":"2016-12-12","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC to reflect the results of a female rat fertility and early embryonic development study (Study No. 497280)."}, {"id":"IB/0002","type":"IB","opinion":"2016-07-08","decision":"2016-12-12","affects":["SmPC","Labelling"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"IB/0001/G","type":"IB","opinion":"2016-03-11","decision":"2016-12-12","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"} ] }, "palbociclib__ibrance": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ibrance-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ibrance-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000253412","type":"N","opinion":"2025-03-06","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Notification acc. Article 61(3) - Update of the package leaflet with revised contact details of local representative and deletion of 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4."}, {"id":"IAIN/0046","type":"IAIN","opinion":"2024-12-10","decision":null,"affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0045","type":"II","opinion":"2024-10-17","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to update information on paediatric population based on final results from study A5481092. This is a Phase 1/2 Study to Evaluate palbociclib in Combination with irinotecan and temozolomide or in Combination with topotecan and cyclophosphamide in Pediatric Patients with Recurrent or Refractory Solid Tumors."}, {"id":"PSUSA/00010544/202308","type":"PSUSA","opinion":"2024-03-21","decision":"2024-05-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - palbociclib"}, {"id":"IAIN/0044","type":"IAIN","opinion":"2024-05-14","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010544/202208","type":"PSUSA","opinion":"2023-03-30","decision":"2023-05-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - palbociclib"}, {"id":"II/0040","type":"II","opinion":"2023-03-30","decision":"2023-05-26","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy and safety information based on final OS results from study A5481008 (PALOMA-2, “A Randomized, Multicenter, Double-blind Phase 3 Study of PD-0332991 (Oral CDK 4/6 Inhibitor) Plus Letrozole Versus Placebo Plus Letrozole for the Treatment of Postmenopausal Women with ER (+), HER2 (-) Breast Cancer Who Have Not Received Any Prior Systemic Anti-Cancer Treatment For Advanced Disease”) to fulfil REC 2. In addition, the MAH took the opportunity to align Annex II with the current QRD template."}, {"id":"II/0038/G","type":"II","opinion":"2022-07-21","decision":"2023-05-26","affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update the primary target organ findings and development toxicity wording. In addition, the MAH took the opportunity to update the list of local representatives (Belgium, Luxembourg, Germany and the Netherlands) in the Package Leaflet. A.6: Update of palbociclib ATC code based on the last revised classification of the Cyclin-dependent kinase (CDK) inhibitors made by the WHO."}, {"id":"R/0034","type":"R","opinion":"2021-05-20","decision":"2021-07-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010544/202008","type":"PSUSA","opinion":"2021-03-25","decision":"2021-05-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - palbociclib"}, {"id":"N/0031","type":"N","opinion":"2020-11-27","decision":"2021-05-19","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0032","type":"IB","opinion":"2020-11-09","decision":"2021-05-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0028/G","type":"IB","opinion":"2020-06-26","decision":"2021-05-19","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.6.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that affects the product information"}, {"id":"X/0018","type":"X","opinion":"2019-12-12","decision":"2020-02-13","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to introduce a new pharmaceutical form (film-coated tablets) associated with new strengths."}, {"id":"N/0026","type":"N","opinion":"2019-11-13","decision":"2020-02-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0024","type":"II","opinion":"2019-10-31","decision":"2020-02-13","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the final report from a non-clinical study (PD-0332991) evaluating the correlation of palbociclib response to RB1 status."}, {"id":"II/0016","type":"II","opinion":"2019-11-14","decision":"2020-02-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC based on the final results from the pivotal Study A5481023 (A double blind, Phase 3 trial of fulvestrant with or without palbociclib in pre- and postmenopausal women with hormone receptor positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy) listed as a recommendation at the time of initial MA. The package leaflet is updated accordingly. The MAH also took the opportunity to update the list of local representatives in the PL."}, {"id":"II/0019/G","type":"II","opinion":"2019-10-17","decision":"2019-11-19","affects":["SmPC","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add ILD/pneumonitis as ADRs together with relevant discontinuation recommendations and a warning based on a safety cumulative review. The Package Leaflet is updated accordingly. The RMP is updated to reclassify the risk of ILD/pneumonitis from an important potential to an important identified risk. Furthermore, long term use has been removed from missing information in the list of safety concerns. In addition, the due date for submission of the final CSR of study A5481027 listed as a Category 3 study in the RMP is updated. The updated RMP version 1.6 is agreed."}, {"id":"II/0017/G","type":"II","opinion":"2019-02-14","decision":"2019-10-24","affects":["SmPC","PL"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to include information from two completed non-clinical studies: a 6-month carcinogenicity study in mice (20084764), and a 2-year carcinogenicity study in rats (20066483). Furthermore, the MAH submitted the final report from the non-clinical study 20084675, a Pre- and Postnatal Developmental Toxicity Study in rats. The MAH took the opportunity to introduce minor editorial changes in SmPC and PL."}, {"id":"II/0011","type":"II","opinion":"2018-11-29","decision":"2019-10-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of section 5.1 of the SmPC to update the clinical efficacy data from pivotal Phase 3 Study A5481008 (PALOMA-2), a study of IBRANCE in combination with letrozole to, to include the results from recent analyses of the study with a data cut-off date of 31 May 2017; in addition, the MAH took the opportunity to update section 4.2 to include a clarification that when co-administered with an aromatase inhibitor, the latter should be administered according to the dose schedule reported in the Summary of Product Characteristics. In addition, minor editorial typos have been corrected in the SmPC and PL."}, {"id":"IB/0023/G","type":"IB","opinion":"2019-07-03","decision":"2019-10-24","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change to an approved stability protocol"}, {"id":"T/0014","type":"T","opinion":"2018-07-11","decision":"2018-07-30","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0010/G","type":"IB","opinion":"2018-02-06","decision":"2018-07-30","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"N/0001","type":"N","opinion":"2016-11-28","decision":"2018-01-24","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0007","type":"II","opinion":"2017-12-14","decision":"2018-01-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC to reflect the results of PK studies on the impact of hepatic impairment (Study A5481013) and the impact of renal impairment (Study A5481014). The RMP (version 1.4) is amended to reflect the completion of these studies."}, {"id":"II/0006","type":"II","opinion":"2017-12-14","decision":"2018-01-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8 and 5.1 of the SmPC in order to reflect independently-reviewed PFS results of study A5481008 (PALOMA-2) and of the Phase 2 portion of the A5481010 single-arm study; the information on ethnicity was also updated in Section 5.2 of the SmPC based on the results of the A5481010 study in Japanese patients."}, {"id":"IB/0004","type":"IB","opinion":"2017-03-28","decision":"2018-01-24","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "panitumumab__vectibix": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vectibix-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"II/0105","type":"II","opinion":"2025-03-13","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the information regarding the incidence of infusion-related reactions to reflect the total number of subjects. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial and administrative changes to the PI and to bring it in line with the latest QRD template version 10.4, and to update the list of local representatives in the Package Leaflet."}, {"id":"IG/1743","type":"IG","opinion":"2024-06-28","decision":null,"affects":["Annex II"],"codes":["A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"II/0097","type":"II","opinion":"2021-10-21","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to add the risk of corneal perforation to the risks of keratitis and ulcerative keratitis and to add corneal perforation (including keratorhexis, which also includes lowest level term corneal rupture) to the list of the adverse reactions, respectively following a safety evaluation. The package leaflet has been updated accordingly. In addition, the applicant took the opportunity to remove frequency information due to variations in case frequency in section 4.8 of the SmPC and section 4 of the PL. Furthermore, the PI is being brought in line with the latest QRD template (version 10.2) and minor editorial changes was made in the PL."}, {"id":"IA/0100","type":"IA","opinion":"2022-07-05","decision":"2022-10-14","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00002283/202009","type":"PSUSA","opinion":"2021-05-20","decision":"2021-07-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - panitumumab"}, {"id":"R/0094","type":"R","opinion":"2019-07-25","decision":"2019-09-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0093","type":"II","opinion":"2019-07-11","decision":"2019-09-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Submission of RMP version 24 for panitumumab to align the important identified and potential risks and missing information in line with the EMA Guideline on Good Pharmacovigilance Practices Module V (Revision 2). As a consequence Section D in Annex II of the Product Information has been updated to reflect removal of the additional risk minimisation measures. The MAH is taking the opportunity to make corrections to the section 4.2 and 4.4 of the SmPC in order to include the table on dose modification previously located in section 4.4. Section 4.4 of the SmPC and package leaflet are also updated to implement the latest excipient guidelines recommendation wording on sodium Content."}, {"id":"II/0086","type":"II","opinion":"2018-01-25","decision":"2018-12-18","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Section 4.4 and section 4.8 of the SmPC and relevant sections of the PL have been updated to reflect a re-analysis of the safety information. No additional risks were added to the Special warnings and precautions for use Section 4.4 and no adverse drug reactions were added or deleted from Section 4.8 of the Vectibix SmPC, changes mainly affect the overall incidence, severity, and seriousness of some of the currently labelled adverse drug reactions from pooling all indications into one table or a renaming of some of the terms."}, {"id":"IG/0946","type":"IG","opinion":"2018-06-04","decision":"2018-12-18","affects":["PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0080","type":"II","opinion":"2017-02-23","decision":"2018-01-30","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH has submitted data to fulfil the Annex II obligation “To submit results of biomarker analyses from the Vectibix clinical programme including Study 20080763 (according to Supplementary Statistical Analysis Plan dated 20 September 2013), Study 20070820 and Study 20060447. Analyses are subject to assay development, qualification, validation (where appropriate), sample availability, and appropriate informed consent”. No relevant biomarker could be identified in addition to RAS from the results of these analyses and the results do not impact the current benefit-risk balance of Vectibix."}, {"id":"IG/0853","type":"IG","opinion":"2017-11-10","decision":"2018-01-30","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0085","type":"IAIN","opinion":"2017-03-10","decision":"2018-01-30","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0079","type":"II","opinion":"2016-11-10","decision":"2017-02-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0076/G","type":"II","opinion":"2016-09-15","decision":"2017-02-27","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.b","C.I.4"],"outcome":"accepted","kind":"other","sections":["6.6"],"scope":"Update of section 6.6 of the SmPC to improve the descriptions of product appearance within the vial, a specification that the medicinal product should be withdrawn from vials via a 21-guage or smaller hypodermic needle, and further emphasis that Vectibix vials are intended for single-use only. In addition, the MAH is taking the opportunity to delete the 10 mL pack size (EU/1/07/423/002)."}, {"id":"IB/0075","type":"IB","opinion":"2016-03-31","decision":"2017-02-27","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IA/0070","type":"IA","opinion":"2015-04-29","decision":"2016-04-13","affects":["Annex II"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0065","type":"II","opinion":"2015-02-26","decision":"2015-03-31","affects":["SmPC"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","5.1"],"scope":"Extension of Indication to include use in the first-line setting in combination with FOLFIRI in the treatment of adult patients with wild-type RAS metastatic colorectal cancer (mCRC) for Vectibix; as a consequence, sections 4.1 and 5.1 of the SmPC have been updated. In addition, the MAH took the opportunity to introduce minor editorial updates throughout the PI."}, {"id":"II/0063","type":"II","opinion":"2014-12-18","decision":"2015-03-31","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 of the SmPC to add the new ADRs ‘urinary tract infection’, ‘dry lips’, ‘hyperhidrosis’ and ‘dermatitis’, and update of the efficacy data in section 5.1 of the SmPC based on the results from the wild-type RAS tumour analysis of study 20050181. Further, some of the Kirsten rat sarcoma-2 viral oncogene (KRAS) (exon 2) data has been deleted from Section 5.1 of the SmPC to ensure that concise and appropriate information is provided to physicians. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet."}, {"id":"R/0064","type":"R","opinion":"2014-11-20","decision":"2015-01-15","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0061","type":"N","opinion":"2014-05-27","decision":"2014-12-05","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0056","type":"II","opinion":"2014-04-25","decision":"2014-12-05","affects":["SmPC","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"R/0054","type":"R","opinion":"2013-12-19","decision":"2014-02-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0050","type":"II","opinion":"2013-06-27","decision":"2013-07-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.5","5.1"],"scope":"Restriction of the indication for the treatment of colorectal cancer to patients with wild-type RAS tumours for Vectibix, further to the CHMP request to update the PI in line with new biomarker data As a consequence, sections 4.1 and 5.1 of the SmPC are updated. In addition, sections 4.2, 4.3, 4.4 and 4.5 of the SmPC are updated in order to amend the safety information regarding use of Vectibix in patients with mutant RAS tumours. The Package Leafle is updated in accordance. In addition, the MAH took the opportunity to update the list of local representatives and to add the details of the Croatian local representative in the Package Leaflet."}, {"id":"R/0043","type":"R","opinion":"2012-11-15","decision":"2013-01-14","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0042","type":"IAIN","opinion":"2012-08-15","decision":"2012-10-25","affects":["Annex II","PL"],"codes":["B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"II/0039/G","type":"II","opinion":"2012-07-19","decision":"2012-08-23","affects":["Annex II"],"codes":["B.I.a.1.e","B.II.b.2.a","B.I.b.1.z","B.I.a.4.z","B.III.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Additional site for the manufacture of the active substance and control of the active substance and finished product"}, {"id":"II/0038","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC in order to modify the warning on avoidance of pregnancy and breast-feeding following Vectibix treatment. The Package Leaflet is updated in accordance. In addition, minor changes to section 4.6 of the SmPC and to corresponding information in the PL are made."}, {"id":"II/0037","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to amend the warning on dermatological reactions to include necrotising fasciitis as possible complication of such reactions following relevant cases reported in PSUR7. The description of skin and subcutaneous tissue adverse events in section 4.8 of the SmPC is also amended to include this information. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make minor changes to section 4.8 of the SmPC and to the Package Leaflet and to update the list of local representatives in the Package Leaflet."}, {"id":"R/0034","type":"R","opinion":"2011-12-15","decision":"2012-02-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0032","type":"II","opinion":"2011-12-15","decision":"2012-01-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to reinforce the warning regarding pulmonary complications following newly identified Interstitial Lung Disease (ILD) cases from a post-marketing Japanese study and to add ILD as an ADR with unknown frequency. The warnings on pulmonary complications, electrolyte disturbances and acute renal failure in case of severe diarrhoea in section 4.4 of the SmPC were further updated as requested by CHMP following the review of PSUR 6. The PL was amended accordingly."}, {"id":"II/0017","type":"II","opinion":"2011-09-22","decision":"2011-11-10","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication To extend the metastatic colorectal cancer indication to include the use of panitumumab in combination with FOLFOX in first line treatment and with FOLFIRI in second line treatment after failure of first-line fluoropyrimidine-based chemotherapy (excluding irinotecan), in patients with wild-type KRAS (Kirsten rat sarcoma) tumours based on safety and efficacy results from two pivotal phase 3 clinical studies (20050203 and 20050181) and other supportive clinical studies."}, {"id":"IA/0030/G","type":"IA","opinion":"2011-05-31","decision":null,"affects":["Annex II"],"codes":["A.4","A.5.b","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS; Administrative change - Change in the name and/or address of a manufacturer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Deletion of manufacturing sites"}, {"id":"II/0025","type":"II","opinion":"2011-04-14","decision":"2011-05-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with the addition of keratitis/ulcerative keratitis requested in follow up to the assessment of PSUR 5. The PL was amended accordingly. The MAH took the opportunity to implement one QRD SmPC change and to make editorial changes to the PL. Finally, the version number of the DDPS was deleted from Annex II."}, {"id":"R/0018","type":"R","opinion":"2010-09-27","decision":"2010-12-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IA/0023/G","type":"IA","opinion":"2010-11-09","decision":null,"affects":["Annex II"],"codes":["C.I.9.d","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the safety database; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"IA/0019/G","type":"IA","opinion":"2010-08-25","decision":null,"affects":["Annex II"],"codes":["C.I.9.c","C.I.9.h","C.I.9.i"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system; Changes to an existing pharmacovigilance system as described in the DDPS - Change(s) to a DDPS following the assessment of the same DDPS in relation to another medicinal product of the same MAH"}, {"id":"II/0016","type":"II","opinion":"2010-03-18","decision":"2010-04-29","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.3","4.4","4.8"],"scope":"Update of sections 4.3, 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL with information on two post-marketing reports of fatal infusion reactions. In addition, section 4.8 of the SmPC and section 4 of the PL were updated regarding Adverse Drug Reactions as requested by the CHMP following PSUR assessments. Furthermore, the MAH took the opportunity to update the List of Local Representatives in the PL. The Product Information has also been updated in line with the latest QRD template."}, {"id":"R/0012","type":"R","opinion":"2009-12-17","decision":"2010-03-15","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0010","type":"II","opinion":"2009-02-19","decision":"2009-04-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of the SPC sections 4.4 and 4.8 and corresponding changes to the Package Leaflet with respect to a review of safety information related to dermatitis acneiform, infusion reactions, renal failure and gastrointestinal disorders and update of SPC sections 4.4 and 5.1 to reflect further analysis related to the PACCE (20040249) clinical investigation, as requested by the CHMP following the assessment of SOB 04. A minor editorial change has also been introduced in the Labelling."}, {"id":"II/0008","type":"II","opinion":"2008-11-20","decision":"2008-12-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","6.3"],"scope":"Update of the SPC in section 4.4 (Special Warnings and precautions for use) related to the information on hypomagnesaemia and other electrolyte disturbances. In addition, section 6.3 (Shelf life) is updated to modify the recommendation related to the permitted storage of Vectibix after dilution for clarity purposes. The package leaflet has been revised accordingly."}, {"id":"II/0006","type":"II","opinion":"2008-09-25","decision":"2008-10-24","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The Marketing Authorisation Holder applied to update the Detailed Description Pharmacovigilance Systems (DDPS) (Version 3.0). Consequently, Annex II has been updated using standard text including the new version numbers of these documents."}, {"id":"II/0004","type":"II","opinion":"2008-06-26","decision":"2008-08-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SPC to include pulmonary embolism as an adverse reaction. The Package Leaflet has been updated accordingly. Further minor editorial corrections to the Labelling following specimen review have also been made."}, {"id":"IB/0005","type":"IB","opinion":"2008-06-18","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"} ] }, "panobinostat__farydak": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/farydak-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"II/0030","type":"II","opinion":"2024-11-28","decision":null,"affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of an updated RMP version 7.1 in order to align the RMP with GVP V and GVP XVII. As a consequence, the MAH proposes to remove severe haemorrhage and severe infections (including sepsis/pneumonia/reactivation of hepatitis B infection) as important identified risks, and developmental toxicity, carcinogenicity/second primary malignancy (SPM), and medication error as important potential risks. In addition, the MAH proposes to revise the Annex II to reflect the removal of the Patient Card and educational programme as additional risk minimisation measures."}, {"id":"IAIN/0028","type":"IAIN","opinion":"2023-10-12","decision":"2024-11-04","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"T/0027","type":"T","opinion":"2023-03-01","decision":"2023-04-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0023","type":"IAIN","opinion":"2021-06-21","decision":"2022-07-08","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0025","type":"IA","opinion":"2022-03-31","decision":"2022-07-08","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00010409/201908","type":"PSUSA","opinion":"2020-03-26","decision":"2020-06-02","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - panobinostat"}, {"id":"R/0020","type":"R","opinion":"2020-02-27","decision":"2020-04-28","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"T/0018","type":"T","opinion":"2019-10-15","decision":"2019-11-04","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IA/0012","type":"IA","opinion":"2018-06-18","decision":"2019-06-06","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"T/0011","type":"T","opinion":"2018-03-20","decision":"2018-04-12","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00010409/201608","type":"PSUSA","opinion":"2017-03-23","decision":"2017-06-23","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - panobinostat"}, {"id":"II/0003","type":"II","opinion":"2016-02-25","decision":"2017-02-16","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC in order to amend the safety information with a recommendation for pregnancy testing prior to treatment with Farydak, as a cautionary measure, in the Product Information. The Package Leaflet and the RMP (finally agreed version: 2.4) are updated in accordance."}, {"id":"II/0001","type":"II","opinion":"2016-02-25","decision":"2017-02-16","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the safety information with regard to the key secondary endpoint of overall survival in the study D2308 to fulfil an Annex II condition (ANX 001). The Annex II of the product information is updated accordingly to remove the condition. As a consequence the RMP ver.2.2 is provided. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct an oversight in the Annex IIIA and add the Days and Weeks in section 5 under ‘Other’ in alignment with the approved blister foil mock-ups."}, {"id":"IB/0005/G","type":"IB","opinion":"2016-09-23","decision":"2017-02-16","affects":["SmPC","PL"],"codes":["A.4","B.I.b.2.c","B.I.d.1.z","B.II.d.2.a","B.II.f.1.b.1","B.III.1.b.2","B.III.1.b.3","B.III.1.b.4","B.I.b.2.z","B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of a new/updated or deletion of Ph. Eur. TSE Certificate of Suitability - Updated certificate from an already approved manufacturer Submission of a new/updated or deletion of Ph. Eur. TSE Certificate of Suitability - Deletion of certificates (in case multiple certificates exist per material)"} ] }, "pazopanib__votrient": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/votrient-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/votrient-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IAIN/0081/G","type":"IAIN","opinion":"2024-12-18","decision":null,"affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"N/0075","type":"N","opinion":"2023-04-20","decision":"2024-07-19","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0076/G","type":"IAIN","opinion":"2023-08-11","decision":"2024-07-19","affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0068","type":"II","opinion":"2021-10-07","decision":"2022-07-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0067/G","type":"II","opinion":"2021-06-10","decision":"2022-07-08","affects":["SmPC","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of section 4.8 of the SmPC in order to add hepatic failure to the list of adverse reactions reported in patients with soft tissue sarcoma (STS)with the frequency not known. The Package Leaflet is updated accordingly. C.I.4 Update of section 4.4 of the SmPC in order to update the information on studies with pazopanib in combination with other systemic anti-cancer therapies which were terminated early due to concerns over increased toxicity and/or mortality. Type IA A.6 Update of section 5.1 of the SmPC with the updated ATC code L01EX03 released by WHO."}, {"id":"IAIN/0070","type":"IAIN","opinion":"2021-09-30","decision":"2022-07-08","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0059","type":"II","opinion":"2020-11-12","decision":"2020-12-17","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"To update sections 4.2, 4.8, 5.1 and 5.2 of the SmPC based on results from studies 2012-001306-20 (ADVL0815 / PZP114411) and study 2013-003595-12 (ADVL1322 / VEG116731 / PZP034X2203) listed in the agreed PIP; these are a phase 1 clinical trial of single-agent pazopanib in children with a relapsed or refractory solid (including CNS) tumour, and a therapeutic-exploratory (phase 2) clinical trials of single-agent pazopanib in children (including adolescents) and young adults with a refractory tumour."}, {"id":"IB/0061","type":"IB","opinion":"2020-10-06","decision":"2020-12-17","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0060","type":"IB","opinion":"2020-07-17","decision":"2020-12-17","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0062/G","type":"IAIN","opinion":"2020-10-16","decision":"2020-12-17","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.2","B.II.b.2.c.1","B.II.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place"}, {"id":"PSUSA/00002321/201910","type":"PSUSA","opinion":"2020-05-28","decision":"2020-07-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pazopanib"}, {"id":"IAIN/0058/G","type":"IAIN","opinion":"2020-02-07","decision":"2020-07-27","affects":["Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Administrative change - Deletion of manufacturing sites; Replacement or addition of a manufacturing site for the FP - Secondary packaging site"}, {"id":"IA/0056","type":"IA","opinion":"2019-11-14","decision":"2020-07-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"T/0046","type":"T","opinion":"2018-03-26","decision":"2018-05-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0043","type":"II","opinion":"2018-01-18","decision":"2018-05-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the frequency of the adverse drug reaction ‘infection’ from uncommon to common. In addition, the Marketing authorisation holder (MAH) took the opportunity to correct some discrepancies in sections 4.4, 4.5 and 4.8 of the SmPC. The PL is updated accordingly."}, {"id":"R/0042","type":"R","opinion":"2017-11-09","decision":"2018-01-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0039","type":"II","opinion":"2016-11-10","decision":"2017-09-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 to add the adverse reaction Polycythaemia with the frequency uncommon. This variation, based on cumulative review of all cases, is provided following the PRAC request on the signal assessment report EPITT no 18660. The Package Leaflet is updated accordingly."}, {"id":"II/0038","type":"II","opinion":"2016-10-13","decision":"2017-09-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of SmPC section 4.6 to add male contraception wording following a review of pazopanib according to the MAH’s guideline on prevention of pregnancies. The Package Leaflet is proposed to be updated accordingly. An updated RMP version 16 is agreed. In addition, the MAH took the opportunity to bring the Product Information in line with the latest QRD template version 10 and combine the SmPC of the 2 tablets strengths."}, {"id":"II/0033","type":"II","opinion":"2016-02-25","decision":"2016-07-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of section 4.4 and 5.1 of the SmPC in order to update pharmacogenomics information following meta-data analysis (study number 201761) of additional clinical trials. In addition, the MAH took the opportunity to add footnote in Table 3 in section 4.8 of the SmPC to align with Table 2 of the same section. Moreover, the revised RMP version 15.1 has been agreed."}, {"id":"II/0032/G","type":"II","opinion":"2015-12-17","decision":"2016-07-14","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update safety information following completion of two carcinogenicity studies in mice and rats. In addition, the MAH submitted a study on the induction of cytochrome P450 (CYP) mRNA expression in mice. Moreover, the revised RMP version 15 has been submitted."}, {"id":"IAIN/0031/G","type":"IAIN","opinion":"2015-07-13","decision":"2016-07-14","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00002321/201410","type":"PSUSA","opinion":"2015-05-21","decision":"2015-07-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pazopanib"}, {"id":"II/0029/G","type":"II","opinion":"2015-04-23","decision":"2015-07-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Based on clinical trials and the MAH’s safety review, update of wording of sections 4.4 and 4.8 of SmPC to add Interstitial Lung Disease(ILD)/Pneumonitis. The PL has been updated accordingly. Following the study VEG 108844 results, update of section 4.4 of SmPC to add more information on myocardial dysfunction. Following the review of safety data from the sarcoma studies, update of section 4.4 of SmPC to correct the number of reported cases of Congestive Heart Failure. The RMP has been updated accordingly."}, {"id":"T/0030","type":"T","opinion":"2015-03-30","decision":"2015-05-05","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation Transfer from Glaxo Group Ltd. to Novartis Europharm Limited. Transfer of Marketing Authorisation"}, {"id":"II/0027/G","type":"II","opinion":"2014-11-20","decision":"2015-01-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information with regards to hepatic function, adverse events in the Asian population and the risk of retinal tears and retinal detachment. In addition, the MAH took the opportunity to update the allocated frequency categories for existing ADRs in section 4.8 of the SmPC. The Package Leaflet is updated accordingly. A revised RMP version 12 was provided as part of the application."}, {"id":"II/0026","type":"II","opinion":"2014-11-20","decision":"2015-01-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC further to submission of the results of Study ADVL0815 (PZP114411), a Phase I Study of Pazopanib as a Single Agent for Children with Relapsed or Refractory Solid Tumours, including central nervous system (CNS) tumours."}, {"id":"II/0025","type":"II","opinion":"2014-09-25","decision":"2015-01-15","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update the efficacy information based on the final study report for study VEG108844. In addition PAM-ANX-012 and PAM-REC-011 have been fulfilled and Annex II has been updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2013-12-18","decision":"2015-01-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0018","type":"II","opinion":"2013-05-30","decision":"2013-07-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order update the safety information to include the need for earlier and more frequent liver toxicity monitoring based on new safety data from study VEG108844. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI has been updated according to the latest QRD template version 9."}, {"id":"IG/0279","type":"IG","opinion":"2013-04-18","decision":"2013-07-01","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"R/0017","type":"R","opinion":"2013-03-21","decision":"2013-06-14","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0016/G","type":"II","opinion":"2012-12-13","decision":"2013-05-03","affects":["SmPC","PL"],"codes":["C.I.4","C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Variations related to significant modifications of the SPC due in particular to new quality, pre-clinical, clinical or pharmacovigilance data; Implementation of change(s) requested following the assessment of an USR, class labelling, a PSUR, RMP, FUM/SO, data submitted under A 45/46, or amendments to reflect a Core SPC - Changes with NO new additional data are submitted by the MAH"}, {"id":"II/0015","type":"II","opinion":"2012-09-20","decision":"2012-10-24","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC in order to add information on the interaction of pazopanib with irinotecan when administered in combination with cetuximab based on results from study VEG108925. These changes were requested further to the assessment of follow up measure FU2 008.1."}, {"id":"II/0014","type":"II","opinion":"2012-07-19","decision":"2012-08-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5"],"scope":"Update of section 4.5 of the SmPC in order to add information on interaction with esomeprazole further to the results of a study conducted to fulfil FUM 007. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to make minor editorial change to section 4.2 of the SmPC."}, {"id":"II/0007","type":"II","opinion":"2012-05-24","decision":"2012-08-03","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.3"],"scope":"Update of sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.3 of the SmPC in order to extend the indication of Votrient for the treatment of patients with advanced Soft Tissue Sarcoma (STS). The Package Leaflet is updated accordingly."}, {"id":"II/0011","type":"II","opinion":"2012-04-19","decision":"2012-05-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the Summary of the Product characteristic (SmPC) to include information on interaction with ketoconazole, following the assessment of final study report for study VEG113971 (an open-label study in cancer patients to evaluate the effects of ketoconazole and the effects of increased gastric pH on the pharmacokinetics of orally administered pazopanib). This variation application addresses partly Follow Up Measure (FUM) 007."}, {"id":"R/0012","type":"R","opinion":"2012-03-15","decision":"2012-05-22","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0009","type":"II","opinion":"2012-02-16","decision":"2012-03-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.3","4.4","5.2"],"scope":"Update of sections 4.2, 4.3, 4.4 and 5.2 of the SmPC in order to include updated recommendations and pharmacokinetic data in hepatic impaired patients based on the results from the final report of study NCI 8063 (VEG110827). This variation application addresses Follow Up Measure (FUM) 006."}, {"id":"II/0008","type":"II","opinion":"2011-09-22","decision":"2011-10-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of Section 5.1 of the SmPC to include results from the final overall survival analysis from study VEG105192, proposed by the MAH further to the assessment of FUM 009."}, {"id":"II/0006","type":"II","opinion":"2011-09-22","decision":"2011-10-24","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC on the increased toxicity and mortality observed when used in combination with the anti-cancer medicinal products premetrexed and lapatinib based on the findings from studies VEG111128 and VEG105281, respectively, and update of sections 4.4 and 4.8 of the SmPC to include information on the risk of serious infections. These changes were requested further to the assessment of PSUR 1. The PL has been updated accordingly."}, {"id":"II/0005","type":"II","opinion":"2011-09-22","decision":"2011-10-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of sections 4.4 and 4.5 of the SmPC on the increased risk of alanine aminotransferase (ALT) elevations in the case of concomitant use with simvastatin and other statins based on the results of a meta-analysis in eleven clinical studies (VEG115003). The PL has been updated accordingly. In addition the MAH took the opportunity to update the date of the latest renewal in section 9 of the SmPC."}, {"id":"R/0003","type":"R","opinion":"2011-02-17","decision":"2011-05-06","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0001","type":"II","opinion":"2011-03-17","decision":"2011-05-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC to provide updated recommendation for patients with mild hepatic impairment further to new pharmacokinetic data available in this patient population. In addition minor editorial amendments have been implemented in the SmPC."}, {"id":"II/0002","type":"II","opinion":"2010-12-16","decision":"2011-02-01","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Changes in section 4.4 of the SmPC to reflect updated recommendations on the risk of hypertension following the evaluation of reports of hypertension from the MAH safety database and the renal cell carcinoma (RCC) clinical trial population. In addition, the date of first authorization has been included in the SmPC and marketing authorisation numbers have been included in the SmPC and Labelling. Finally, minor editorial changes have been implemented in the SmPC and Package Leaflet."}, {"id":"IG/0034/G","type":"IG","opinion":"2011-01-06","decision":null,"affects":["Annex II"],"codes":["C.I.9.b","C.I.9.c","C.I.9.e","C.I.9.g","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the contact details of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Changes in the major contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations and described in the DD; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the site undertaking pharmacovigilance activities."} ] }, "peginterferon-alfa-2a__pegasys": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/pegasys-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/pegasys-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000368501","type":"IB","opinion":"2026-09-22","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["Q.II.e.6.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of a new pack size or change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"EMA/VR/0000307242","type":"IAIN","opinion":"2025-10-31","decision":null,"affects":["PL"],"codes":["B.II.b.2.c.1","B.II.b.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Secondary packaging site"}, {"id":"II/0119/G","type":"II","opinion":"2024-06-27","decision":"2024-08-05","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.8","5.1","5.2"],"scope":"Grouped application consisting of: Extensions of indication to include treatment of Polycythaemia Vera (PV) and Essential thrombocytopenia (ET) for PEGASYS for the pre-filled syringes, based on published data of clinical studies conducted in support of the efficacy and safety of Pegasys for the treatment of ET and PV. As a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 10.2 of the RMP has also been submitted. Furthermore, the PI is brought in line with the latest QRD template version 10.3."}, {"id":"IAIN/0118/G","type":"IAIN","opinion":"2023-10-11","decision":"2024-08-05","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0112","type":"II","opinion":"2022-09-29","decision":"2022-11-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include information on post-treatment recovery in growth based on final results from study YV25718 listed as a category 3 study in the RMP; this is a Phase IIIb parallel group, open label study of pegylated interferon alfa-2a monotherapy (PEG-IFN, RO0258310) compared to untreated control in children with HBeAg-Positive Chronic Hepatitis B in the immune active phase. The RMP version 9.1 has also been submitted. In addition, the MAH took the opportunity to implement editorial changes in the Package Leaflet."}, {"id":"IAIN/0111","type":"IAIN","opinion":"2021-12-17","decision":"2022-11-28","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0110","type":"T","opinion":"2021-07-28","decision":"2021-08-12","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0102","type":"N","opinion":"2018-08-09","decision":"2021-04-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0108","type":"IB","opinion":"2021-03-09","decision":"2021-04-16","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0104","type":"IB","opinion":"2020-10-01","decision":"2021-04-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0106","type":"IAIN","opinion":"2020-12-08","decision":"2021-04-16","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0103","type":"IA","opinion":"2020-05-07","decision":"2021-04-16","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Change in type/addition of a new container - Deletion of an immediate packaging container without a complete deletion of a strength or pharmaceutical form"}, {"id":"T/0100","type":"T","opinion":"2018-02-20","decision":"2018-03-15","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0092","type":"II","opinion":"2017-05-05","decision":"2017-11-10","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of section 5.1 of the SmPC in order to add information on the predictive value of on-treatment biomarkers for final treatment response based on the final report from a systematic review and individual patient data meta-analysis of PEG-IFN studies. A cross-reference is added to section 4.2 of the SmPC accordingly."}, {"id":"II/0091","type":"II","opinion":"2017-10-12","decision":"2017-11-10","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the use of Pegasys in the treatment of paediatric patients from 3 to less than 18 years of age with chronic Hepatitis B in the immune-active phase; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated in order to add efficacy and safety information from study YV25718. The Package Leaflet is updated in accordance. An updated RMP (version 8.3) was agreed."}, {"id":"IA/0095","type":"IA","opinion":"2017-06-16","decision":"2017-11-10","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Deletion of a pack size(s)"}, {"id":"N/0090","type":"N","opinion":"2016-08-09","decision":"2016-10-14","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0089","type":"II","opinion":"2016-09-15","decision":"2016-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update the information on the use of the medicinal product in patients with mild, moderate and severe renal impairment. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder took the opportunity to bring the PI in line with the latest QRD template version 9.1."}, {"id":"IB/0087","type":"IB","opinion":"2016-06-14","decision":"2016-08-01","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0082","type":"IB","opinion":"2015-09-08","decision":"2016-08-01","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0085","type":"IAIN","opinion":"2016-01-08","decision":"2016-08-01","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"II/0075","type":"II","opinion":"2014-10-23","decision":"2015-10-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC based on data from the long term follow up study to the paediatric study NV17424. The package leaflet is updated accordingly."}, {"id":"II/0073","type":"II","opinion":"2014-03-20","decision":"2014-04-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication for Pegasys to include the use of other products used for the treatment of Hepatitis C. The PL is updated accordingly."}, {"id":"PSUV/0072","type":"PSUV","opinion":"2014-02-20","decision":"2014-04-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"N/0069","type":"N","opinion":"2013-10-02","decision":"2014-04-23","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0071","type":"II","opinion":"2013-10-24","decision":"2014-04-23","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to include a statement on traceability of biological medicinal products."}, {"id":"II/0070","type":"II","opinion":"2013-10-24","decision":"2014-04-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to include information on use in patients with co-occurring substance use disorder. The PL is updated accordingly. In addition, the MAH took this opportunity to bring the PI in line with the latest QRD template version 9 and to include minor editorial changes and corrections in the SmPC and PL."}, {"id":"X/0059/G","type":"X","opinion":"2013-01-17","decision":"2013-03-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the marketing authorisation to include a new 90 mcg strength of pre-filled syringe and extension of the indication to include the treatment of chronic hepatitis C in paediatric patients aged 5 years and older with consequential changes to the SmPC and PL. The MAH further took the opportunity to update the PI in line with the latest QRD template (version 8.2) and to remove from Annex II the Nutley manufacturing site, which was withdrawn in a previous variation."}, {"id":"N/0063","type":"N","opinion":"2012-03-01","decision":"2012-09-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0055","type":"II","opinion":"2011-10-20","decision":"2011-12-14","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC at the request of the CHMP further to the assessment of PSUR 12 in order to incorporate post-marketing adverse events into the tabulated list of adverse reactions. The PL has been updated accordingly."}, {"id":"IB/0056","type":"IB","opinion":"2011-09-09","decision":null,"affects":["SmPC","Labelling"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Extension of storage period of a biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IA/0053","type":"IA","opinion":"2011-08-10","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.e.6.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that affects the product information"}, {"id":"II/0050","type":"II","opinion":"2011-05-19","decision":"2011-06-29","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"A review of reported relevant prospective cases of maternal and paternal exposure to ribavirin has been carried out. Only a limited number of cases are available. However, a large number of data would be necessary to draw a definitive conclusion on the teratogenic potential of ribavirin. The malformative risk is possible in human, but it is not confirmed. For paternal exposure, the malformative risk is unlikely in humans. Taking into account the number of reference cases outnumbering 300 after paternal exposure with no increase of congenital anomaly risk, it is recommended to remove the requirement of double contraceptive measures for a treated woman and male patient."}, {"id":"II/0047/G","type":"II","opinion":"2011-05-19","decision":"2011-06-29","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.2","B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"To add a new staked-in needle pre-filled syringe in a disposable autoinjector."}, {"id":"II/0048","type":"II","opinion":"2011-03-17","decision":"2011-04-18","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.3","4.5"],"scope":"Update of section 4.3 and 4.5 to include a contraindication for the use of Pegasys in combination with telbivudine. The package leaflet is updated accordingly further to request by the CHMP."}, {"id":"II/0045","type":"II","opinion":"2010-05-20","decision":"2010-07-02","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.3","4.4"],"scope":"Update of Section 4.2, 4.3 and 4.4 of the SmPC with information related to the posology of HIV/HCV co-infected patients and safety related information from study NV18209."}, {"id":"II/0044","type":"II","opinion":"2010-05-20","decision":"2010-07-02","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of Section 4.4 and 4.8 of the SPC to include information on liver and renal transplant rejection. This follows a request of the CHMP made in the context of the assessment of PSUR 9 (period covered: 05.07.07 - 04.07.08). Section 4.8 has been reorganizing for greater clarity. Section 4.2 is updated to provide a clarification. A minor correction has been made to the package leaflet."}, {"id":"II/0043","type":"II","opinion":"2009-09-24","decision":"2009-10-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of Summary of Products Characteristics and Package Leaflet. Update of sections 4.4, 4.5 and 4.8 of the SPC to include a drug-drug interaction between ribavirin and azathioprine and safety information on homicidal ideation. The PL was updated accordingly. The MAH took the opportunity to amend the SPC and product labelling due to a change in the design of the packaging in compliance with QRD. In addition minor corrections have been made to the Greek PL."}, {"id":"II/0042","type":"II","opinion":"2009-07-23","decision":"2009-08-21","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The overall evidence for the use of an 800 mg flat dose of ribavirin in patients with genotype 2/3 treated for 24 weeks is considered sufficiently solid, as comparative studies have not clearly demonstrated any efficacy advantage of a higher dose, to outweigh a higher risk of exposure related adverse effects. No comparative data are presently available concerning the relative efficacy of an 800 mg flat dose and a higher, weight based regimen in patients treated for a shortened duration, the CHMP therefore considered that it is unclear what dose of ribavirin should be used if treatment is started in a patient where a shortened duration of therapy is planned in case of a Rapid Viral Response."}, {"id":"II/0041","type":"II","opinion":"2009-07-23","decision":"2009-08-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Further to the assessment of PSUR 9 (period covered 05.07.07 - 04.07.08) amendments are made to the SPC. In Section 4.4 Sepsis is mentioned in the context of other infections. A warning concerning the relation of serous retinal detachment to pre-disposing autoimmune uveitis/suspected Vogt-Koyanagi-Harada disease is also included and bipolar disorder and mania are mentioned. In Section 4.5 a warning concerning the interaction between Telbivudine and Pegasys and the possible increased risk for peripheral neuropathy is included."}, {"id":"II/0038","type":"II","opinion":"2009-03-19","decision":"2009-04-08","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"II/0036","type":"II","opinion":"2008-10-23","decision":"2008-11-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include the treatment of patients who have failed previous treatment with interferon alfa (pegylated or non-pegylated) in combination therapy with ribavirin."}, {"id":"II/0037","type":"II","opinion":"2008-09-25","decision":"2008-10-30","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SPC further to a request of the CHMP following the evaluation of follow up measure FUM 12. Data from the HALT-C study (NR15963) of HCV non-responder patients with varied degrees of fibrosis is reflected."}, {"id":"II/0035","type":"II","opinion":"2008-04-24","decision":"2008-06-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SPC to include the following adverse reactions; fungal, bacterial and viral infections; cerebral ischaemia; serious retinal detachment; cardiomyopathy; vasculitis; rhabdomyolysis and renal insufficiency further to a request of the CHMP made in the context of the assessment for PSUR 9. The package leaflet is updated accordingly."}, {"id":"II/0033","type":"II","opinion":"2008-04-24","decision":"2008-06-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SPC to shorten the treatment duration in patients with Genotype 2 and 3 with a rapid viral response from 24 weeks to 16 weeks based on a retrospective analysis of study NV17317. The package leaflet is updated accordingly. The MAH takes the opportunity to make corrections to the Romanian and Czech product information."}, {"id":"II/0032","type":"II","opinion":"2007-10-18","decision":"2007-11-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SPC to include the adverse event \"dehydration\" further to a review carried out by the MAH. Furthermore the frequency categories for adverse reactions included in section 4.8 are updated following a request from the CHMP. The MAH also takes the opportunity to make a correction to the frequency category of the adverse event \"weight decreased\" in section 4.8 of the SPC. The package leaflet is updated accordingly. The details of the Estonian local representative are updated in the Package Leaflet."}, {"id":"II/0031","type":"II","opinion":"2007-10-18","decision":"2007-11-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5"],"scope":"Update of sections 4.2, 4.4 and 4.5 of the SPC further to the assessment of a follow-up measure concerning HIV-HCV co-infection to reflect new information about the status of knowledge regarding dosing of HIV-HCV co-infected population and to reflect new precautions regarding the increased risk of anaemia when dosing alfa-interferons with ribavirin and zidovudine. The PL has been updated accordingly."}, {"id":"R/0029","type":"R","opinion":"2007-04-26","decision":"2007-06-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0030","type":"II","opinion":"2007-05-24","decision":"2007-06-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"The section 4.5 was updated following the results of a pharmacokinetic study of 24 chronic hepatitis C patient receiving methadone maintenance therapy. The study showed mean methadone levels 10 to 15% higher than at baseline. The clinical significance of this finding is unknown but patients should be monitored for signs and symptoms of methadone toxicity, specially risk of QTc prolongation in patients on a high dose of methadone."}, {"id":"II/0027","type":"II","opinion":"2007-01-24","decision":"2007-03-01","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of section 4.2 and 5.1 of the SPC to shorten the treatment duration from 48 weeks to 24 weeks in patients with genotype 1 with low viral load and patients with genotype 4 who have a rapid virological response based on the results of a retrospective analysis of two pivotal trials."}, {"id":"II/0024","type":"II","opinion":"2006-11-16","decision":"2007-01-04","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Following PSUR 7 (covering the period 1 February 2005 - 31 January 2006) section 4.8 of the SPC is updated to add the adverse reactions facial palsy, convulsions, diabetic ketoacidosis and erythema multiforme. Section 4.4 is also updated with the risk of serious infections and of uncontrolled hyper- and hypoglycaemia. A warning is also included regarding periodontal disorders. The package leaflet is updated accordingly. The MAH also takes the opportunity to update the list of local representatives for Poland and Iceland in the package leaflet."}, {"id":"II/0025","type":"II","opinion":"2006-10-18","decision":"2006-11-22","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 \"Special warnings and Precautions for use\" and 5.2 \"Pharmacokinetic properties\" of the SPC to include the time for recovery of neutrophil count and to add a new estimate of terminal half life, as requested by the CHMP further to the assessment of a pharmacokinetic and neutrophil recovery substudy on Pegasys."}, {"id":"IA/0028","type":"IA","opinion":"2006-09-28","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0022","type":"II","opinion":"2006-06-28","decision":"2006-07-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","6.4"],"scope":"Update of section 4.4 of the SPC following a class labelling adopted by the CHMP on 23 March 2006 regarding psychiatric disorders. The Package Leaflet has been up dated accordingly. The MAH also takes the opportunity to carry out a minor correction in section 6.4 of the SPC and annexes pertaining to storage conditions to be in line with the QRD template and the MAH also carries out some minor editorial corrections."}, {"id":"II/0021","type":"II","opinion":"2006-04-27","decision":"2006-05-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.3","4.6"],"scope":"Update of section 4.3 of the SPC to withdraw the contraindication of Pegasys during pregnancy and lactation. Section 4.6 of the SPC will also be amended regarding the recommendations on pregnancy and lactation. This change follows the adoption of a class labelling by the CHMP on 26th January 2006 for the Interferons and Ribavirin for pregnancy and lactation. Corresponding revisions to the Package Leaflet are made."}, {"id":"II/0018","type":"II","opinion":"2005-12-14","decision":"2006-01-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics, Labelling and Package Leaflet"}, {"id":"IA/0019","type":"IA","opinion":"2005-10-25","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"II/0011","type":"II","opinion":"2005-01-20","decision":"2005-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"IA/0017","type":"IA","opinion":"2005-02-24","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"IA_43_a_01_ Add./replacement/del. of measuring or administration device - addition or replacement"}, {"id":"II/0009","type":"II","opinion":"2004-12-15","decision":"2005-01-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"IB/0012","type":"IB","opinion":"2005-01-11","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0007","type":"II","opinion":"2004-09-16","decision":"2004-10-29","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"The Marketing Authorisation Holder applied for an extension of the therapeutic indication of all the formulations of Pegasys (peginterferon alfa-2a) to include treatment in combination with ribavirin of adult patients with chronic hepatitis C (CHC) and persistently normal alanine aminotransferase (ALT) levels with consequential changes to Sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SPC. In addition the SPC, labelling and PL were updated in accordnace to the SPC guideline and the latest QRD template."}, {"id":"IB/0010","type":"IB","opinion":"2004-07-21","decision":"2004-07-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size - change in no. of units outside range of appr. pack size"}, {"id":"N/0008","type":"N","opinion":"2004-05-11","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0006","type":"II","opinion":"2003-10-22","decision":"2004-01-14","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of or change(s) to the pharmaceutical documentation"}, {"id":"II/0001","type":"II","opinion":"2003-04-25","decision":"2003-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.4","4.6","4.8","5.1","5.2"],"scope":"Changes were made to section 4.1, 4.2, 4.4, 4.6, 4.8, 5.1 and 5.2 of the SPC. The MAH applied to remove the term \"histologically proven\" from the section 4.1 of the SPC referring to the French Consensus Conference on Hepatitis C where it is stated that biopsy may not be necessary if a decision to treat has been made on other grounds and the primary objective is viral eradication. This is also largely in line with other National Guidelines. The viral eradication rate is sufficiently high for patients with genotype 2/3 that treatment is indicated in many cases even if the histology turns out to be benign. Therefore histology is not always needed."}, {"id":"I/0003","type":"I","opinion":"2002-11-26","decision":"2003-01-14","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Withdrawal of the manufacturing authorisation for a site of manufacture"}, {"id":"I/0002","type":"I","opinion":"2002-11-26","decision":"2003-01-14","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in or addition of manufacturing site(s) for part or all of the manufacturing process"} ] }, "pembrolizumab__keytruda": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/keytruda-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/keytruda-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000336194","type":"II","opinion":"2026-09-17","decision":"2026-10-16","affects":["SmPC","PL"],"codes":["C.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include KEYTRUDA, in combination with enfortumab vedotin, as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment, is indicated for the treatment of adults with resactable muscle invasive bladder cancer (MIBC) who are eligible for cisplatin containing chemotherapy, based on the results from Interim Analysis 1 of the pivotal Study KN-B15 (EV-304); this is a phase 3, randomized, open-label study to evaluate perioperative enfortumab vedotin plus pembrolizumab (MK-3475) versus neoadjuvant gemcitabine and cisplatin in cisplatin-eligible participants with Muscle-Invasive Bladder Cancer."}, {"id":"EMA/VR/0000332176","type":"IB","opinion":"2026-03-18","decision":"2026-06-19","affects":["SmPC"],"codes":["Q.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf life of the finished product based on extrapolation of stability data in accordance with relevant stability guidelines"}, {"id":"EMA/VR/0000317322","type":"II","opinion":"2026-04-30","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of section 4.2, 4.4 and 4.8 of the SmPC in order to reflect information on myocarditis-myositis-myasthenia gravis overlap syndrome based on pembrolizumab clinical trial data and global safety data; the Package Leaflet is updated accordingly."}, {"id":"EMA/VR/0000316576","type":"II","opinion":"2026-05-21","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"A grouped application consisting of: Extension of indication for KEYTRUDA for subcutaneous use to include treatment of melanoma for adolescents aged 12 years and older based on an extrapolation approach from adults to adolescents using pharmacokinetics modelling and simulation. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 48.0 of the RMP is agreed. In addition, the Marketing authorisation holder took the opportunity to implement some minor editorial and formatting changes in the PI."}, {"id":"EMA/VR/0000312515","type":"II","opinion":"2026-05-21","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include KEYTRUDA in combination with enfortumab vedotin, as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment of adults with resectable muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin containing chemotherapy for KEYTRUDA, based on interim results from study KEYNOTE-905, an open label, randomised, interventional phase 3 study. As consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 48.0 of the RMP has also been agreed."}, {"id":"EMA/VR/0000293815","type":"II","opinion":"2026-02-26","decision":"2026-03-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","5.1"],"scope":"Extension of indication to include in combination with paclitaxel, with or without bevacizumab, the treatment of platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1 and who have received one or two prior systemic treatment regimens for KEYTRUDA, based on interim results from study PB96V01MK3475 (KEYNOTE-B96); this is a Phase 3, randomized, double-blind study of pembrolizumab in combination with paclitaxel with or without bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. As a consequence, sections 4.1 and 5.1 of the SmPC are updated."}, {"id":"EMA/X/0000248795","type":"X","opinion":"2025-09-18","decision":"2025-11-17","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension application to introduce a new pharmaceutical form (solution for injection) associated with two new strengths (790 mg and 395 mg) and new route of administration (subcutaneous use). The RMP (version 49.1) is updated in accordance."}, {"id":"EMA/VR/0000264560","type":"II","opinion":"2025-06-19","decision":"2025-10-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on results from study KEYNOTE-158. This is a Phase II study Evaluating Predictive Biomarkers in Subjects with Advanced Solid Tumors. The MAH took also the opportunity to update the list of local representatives."}, {"id":"EMA/VR/0000245108","type":"II","opinion":"2025-09-18","decision":"2025-10-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include, KEYTRUDA as monotherapy, for the treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC) as neoadjuvant treatment, continued as adjuvant treatment in combination with radiation therapy with or without cisplatin and then as monotherapy in adults whose tumours express PD-L1 with a CPS ≥ 1, based on the results of study P689V01MK3475 (KEYNOTE-689); this is a Phase 3, randomised, open-label study evaluating pembrolizumab as neoadjuvant therapy and in combination with standard of care as adjuvant therapy for stage III or IVA, resectable, locoregionally advanced head and neck squamous cell carcinoma."}, {"id":"PSUSA/00010403/202409","type":"PSUSA","opinion":"2025-04-25","decision":"2025-06-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0162","type":"II","opinion":"2024-12-05","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["B.I.a.4.e"],"outcome":"accepted","kind":"other","sections":["6.3"],"scope":"The SmPC section 6.3 has been updated to delete the instruction ‘Protect from light’. The Package Leaflet (PL) is updated accordingly."}, {"id":"II/0161","type":"II","opinion":"2024-12-05","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update information on pericarditis and include the risk of pericarditis under the section “Other immune-mediated adverse reactions” based on post-marketing data and literature. The Package Leaflet is updated accordingly."}, {"id":"II/0160","type":"II","opinion":"2024-11-21","decision":"2025-04-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update information based on the Interim Analysis 7 (IA7) results from the P522V05MK3475 (KEYNOTE-522) study. This is a Phase 3 randomized, double-blind study to evaluate pembrolizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy for triple negative breast cancer (TNBC)."}, {"id":"II/0154","type":"II","opinion":"2025-02-27","decision":"2025-04-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Extension of indication to include in combination with pemetrexed and platinum chemotherapy the first-line treatment of adults with unresectable non-epithelioid malignant pleural mesothelioma for Keytruda, based on final results from study KEYNOTE-483; this is a multicenter, open-label, Phase 2/3 randomized study to evaluate the efficacy and safety of pembrolizumab in combination with pemetrexed/platinum chemotherapy in participants with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). As a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 45.0 of the RMP has also been submitted."}, {"id":"IB/0164","type":"IB","opinion":"2025-01-31","decision":"2025-04-04","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"II/0153","type":"II","opinion":"2024-09-19","decision":"2024-10-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"II/0145","type":"II","opinion":"2024-09-19","decision":"2024-10-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include in combination with chemoradiotherapy (external beam radiation therapy followed by brachytherapy), the treatment of FIGO 2014 Stage III - IVA locally advanced cervical cancer in adults who have not received prior definitive therapy for Keytruda, based on the results from pivotal Phase III study KEYNOTE-A18. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet and the Risk Management Plan version 44 are updated in accordance."}, {"id":"II/0152","type":"II","opinion":"2024-05-02","decision":"2024-08-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on interim results from study KEYNOTE-564; this is a phase 3, randomized, double-blind, placebo-controlled clinical trial of pembrolizumab as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy."}, {"id":"II/0150","type":"II","opinion":"2024-07-25","decision":"2024-08-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include Keytruda in combination with enfortumab vedotin for the first-line treatment of locally advanced or metastatic urothelial carcinoma in adults, based on the final results from KEYNOTE-A39/EV-302: “An open label, randomized, controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab versus chemotherapy alone in previously untreated locally advanced (LA) or metastatic urothelial cancer (mUC)”. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 45.1 of the RMP has also been submitted."}, {"id":"II/0147","type":"II","opinion":"2024-03-14","decision":"2024-08-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-B61; this is a Phase 2, Single-arm, Open-label Clinical Trial of Pembrolizumab Plus Lenvatinib in Participants with First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (nccRCC)."}, {"id":"IB/0156","type":"IB","opinion":"2024-07-08","decision":"2024-08-29","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IAIN/0157","type":"IAIN","opinion":"2024-06-19","decision":"2024-08-29","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0134","type":"II","opinion":"2024-02-22","decision":"2024-03-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant, for the treatment of resectable non small cell lung carcinoma at high risk of recurrence in adults ,for Keytruda based on study KEYNOTE-671, a phase III, randomized, double-blind trial of platinum doublet chemotherapy +/- pembrolizumab as neoadjuvant/adjuvant therapy for participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 42 of the RMP has also been submitted."}, {"id":"II/0139","type":"II","opinion":"2023-11-09","decision":"2023-12-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update clinical information, based on results from study KEYNOTE-716 listed as a PAES in the Annex II. This is a randomized, double-blind phase 3 study of adjuvant therapy with pembrolizumab versus placebo in resected high-risk stage II melanoma. The Annex II is updated accordingly"}, {"id":"II/0138","type":"II","opinion":"2023-11-09","decision":"2023-12-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of indication to include KEYTRUDA in combination with gemcitabine and cisplatin for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults, based on final results from study KEYNOTE-966; this is a Phase 3 randomized, double blind study of Pembrolizumab plus Gemcitabine/Cisplatin versus Placebo plus Gemcitabine/Cisplatin as first-line therapy in participants with advanced and/or unresectable biliary tract carcinoma. As a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 41.0 of the RMP has also been submitted."}, {"id":"II/0135","type":"II","opinion":"2023-10-12","decision":"2023-11-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Extension of indication to include in combination with chemotherapy the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastrooesophageal junction adenocarcinoma in adults whose tumours express PD L1 with a CPS ≥ 1 based on study KEYNOTE-859, a randomised, double-blind phase 3 trial, evaluating KEYTRUDA in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. As a consequence sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"II/0141","type":"II","opinion":"2023-09-14","decision":"2023-10-12","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-826; this is a phase 3 randomized, double-blind, placebo-controlled trial of pembrolizumab (MK-3475) plus chemotherapy versus chemotherapy plus placebo for the first-line treatment of persistent, recurrent, or metastatic cervical cancer. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0136","type":"II","opinion":"2023-08-31","decision":"2023-10-12","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of sections 5.1 of the SmPC in order to provide the final OS data (including analyses/KM plots from favourable prognosis subgroups) following the assessment of procedure II/0104, based on results from study E7080-G000-307/KEYNOTE 581 (REC); A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects with Advanced Renal Cell Carcinoma (CLEAR). In addition, the due date for the final study report of Keynote 054 was updated in Annex II."}, {"id":"II/0121","type":"II","opinion":"2023-09-14","decision":"2023-10-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include Keytruda as monotherapy for the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum-based chemotherapy based on study KEYNOTE-091; an ongoing Phase 3, randomized, triple-blinded, placebo-controlled, multicentre study of pembrolizumab versus placebo in patients with early-stage NSCLC after resection and completion of standard adjuvant therapy. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are being updated and the Annex II and the Package Leaflet are updated in accordance. An updated RMP version 39.0 was also submitted."}, {"id":"IB/0137/G","type":"IB","opinion":"2023-08-04","decision":"2023-10-12","affects":["Annex II"],"codes":["B.I.b.2.e","B.I.z","B.I.a.4.b","B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for AS or starting material/reagent/intermediate - Other changes to a test procedure (including replacement or addition) for the AS or a starting material/intermediate; Quality change - Active substance - Other variation; Change to in-process tests or limits applied during the manufacture of the AS - Addition of a new in-process test and limits; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"II/0133","type":"II","opinion":"2023-07-20","decision":"2023-08-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Extension of indication to include in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy for treatment of locally advanced unresectable or metastatic HER2- positive gastric or gastro-oesophageal junction adenocarcinoma for Keytruda, based on interim results from study KEYNOTE-811, an ongoing Phase 3, double-blind trial comparing trastuzumab plus chemotherapy and pembrolizumab with trastuzumab plus chemotherapy and placebo as first-line treatment in participants with HER2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma; As a consequence, sections 4.1, 4.8, and 5.1 of the SmPC are updated."}, {"id":"II/0132","type":"II","opinion":"2023-03-16","decision":"2023-08-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add optic neuritis to the list of adverse drug reactions (ADRs) with frequency rare based on literature review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"II/0128","type":"II","opinion":"2023-03-09","decision":"2023-08-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update information based on the final OS data for the overall population as well as for MMR subgroups from study 309/KEYNOTE-775 in order to fulfil the Recommendation: REC/033. This Recommendation was agreed to with the approval of study 309/KEYNOTE-775; this is a multicenter, open-label, randomized, phase 3 trial to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in participants with advanced endometrial cancer."}, {"id":"IAIN/0130","type":"IAIN","opinion":"2022-11-17","decision":"2023-08-23","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0126","type":"II","opinion":"2022-09-15","decision":"2022-10-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"To update sections 4.2 and 5.2 of the SmPC to include data for patients with moderate hepatic impairment based on KEYNOTE-240 (a double-blind, randomized, Phase 3 study of pembrolizumab in participants with previously systemically treated advanced HCC) and KEYNOTE-224 (a Phase 2 study of pembrolizumab as monotherapy in participants with advanced HCC). The MAH took the opportunity to make some editorial changes."}, {"id":"II/0122","type":"II","opinion":"2022-06-16","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning for ‘Hypoparathyroidism’ and to add it to the list of adverse drug reactions (ADRs) with frequency rare based on literature references; the Package Leaflet is updated accordingly."}, {"id":"II/0111","type":"II","opinion":"2022-05-19","decision":"2022-06-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, Stage IIC or stage III melanoma and to inlcude the treatment of adolescents aged 12 years and older with advanced melanoma for Keytruda; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 37 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce editorial improvements in the wording of the indication for MSI-H or dMMR cancers in section 4.1 of the SmPC and update the list of local representatives in the Package Leaflet."}, {"id":"PSUSA/00010403/202109","type":"PSUSA","opinion":"2022-04-22","decision":"2022-06-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0110","type":"II","opinion":"2022-04-22","decision":"2022-05-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication for Keytruda in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery of adults with locally advanced, or early-stage triple-negative breast cancer at high-risk of recurrence; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 36.0 of the RMP has also been submitted."}, {"id":"II/0117","type":"II","opinion":"2022-03-24","decision":"2022-04-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Extension of indication to include a new indication for Keytruda, in combination with chemotherapy, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic cervical cancer in adults; as a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 35 of the RMP has also been submitted."}, {"id":"II/0115","type":"II","opinion":"2022-03-24","decision":"2022-04-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-426 listed as imposed PAES in the Annex II; this is a Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in combination with Axitinib versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC). In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0114","type":"II","opinion":"2022-02-17","decision":"2022-04-25","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of sections 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-087 listed as an imposed PAES in the Annex II; this is a multicenter, single-arm, multi-cohort, non-randomized Phase 2 study of IV pembrolizumab in participants with relapsed or refractory classical Hodgkin lymphoma (cHL)."}, {"id":"II/0109","type":"II","opinion":"2022-03-24","decision":"2022-04-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication for KEYTRUDA as monotherapy for the treatment of the following MSI H or dMMR tumours in adults with: -unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy; - advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation; -unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy."}, {"id":"IB/0119","type":"IB","opinion":"2022-01-04","decision":"2022-04-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.7.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of - a pharmaceutical form"}, {"id":"IA/0120","type":"IA","opinion":"2022-02-08","decision":"2022-04-25","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0116","type":"II","opinion":"2021-12-09","decision":"2022-01-24","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of sections 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-177 listed as PAES in Annex II of the Product Information; this is a 2-arm, multicenter, international, randomized, open-label, Phase 3 study evaluating the efficacy and safety of pembrolizumab monotherapy versus globally-accepted SOC therapies for Colorectal carcinoma (CRC) in participants with locally confirmed Deficient mismatch repair (dMMR) or Microsatellite instability-high (MSI-H) unresectable or metastatic CRC who have not received prior chemotherapy for their disease."}, {"id":"II/0108","type":"II","opinion":"2021-12-16","decision":"2022-01-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","5.1"],"scope":"Extension of indication to include the adjuvant treatment in monotherapy of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. As a consequence, sections 4.1, 4.2, and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 34.0 of the RMP has also been submitted."}, {"id":"II/0105","type":"II","opinion":"2021-10-14","decision":"2021-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include pembrolizumab in combination with lenvatinib for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 33.0 of the RMP has also been agreed."}, {"id":"II/0104","type":"II","opinion":"2021-10-14","decision":"2021-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include Keytruda in combination with lenvatinib first line treatment of adults with advanced renal cell carcinoma (RCC); as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 32.1 of the RMP has also been submitted."}, {"id":"II/0099","type":"II","opinion":"2021-09-16","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for Keytruda to include in combination with chemotherapy, treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 32 of the RMP has also been submitted."}, {"id":"IAIN/0112","type":"IAIN","opinion":"2021-08-19","decision":"2021-10-19","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0097","type":"II","opinion":"2021-05-20","decision":"2021-06-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include in combination with platinum and fluoropyrimidine based chemotherapy, first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD L1 with a CPS ≥ 10, based on the results from the pivotal KEYNOTE-590 (KN590) trial. As a consequence, sections 4.1, 4.2, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Minor updates are also included in Annex II of the Product Information. Version of the RMP (Version 31.0) has also been submitted."}, {"id":"PSUSA/00010403/202009","type":"PSUSA","opinion":"2021-04-22","decision":"2021-06-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0102","type":"II","opinion":"2021-04-22","decision":"2021-05-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2, and 5.1 of the SmPC in order to introduce an alternative dosing regimen of 400 mg every 6 weeks (Q6W) for all approved indications based on interim results from study KEYNOTE-555; this is an interventional, PK study in patients with advanced melanoma. Additonal data/analysis from studies KEYNOTE-021, -048, -189, -407 and -426 were provided."}, {"id":"II/0100","type":"II","opinion":"2021-04-15","decision":"2021-05-21","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy data based on interim results from study KEYNOTE-054 listed as a PAES in the Annex II; this is a randomized, double-blind, placebo-controlled phase 3 study evaluating pembrolizumab in the adjuvant therapy of patients with resected high-risk melanoma."}, {"id":"II/0094","type":"II","opinion":"2021-03-25","decision":"2021-05-21","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to update efficacy information based on final results from study KEYNOTE-361 listed as a PAES in the Annex II; this is a Phase III Randomised, Controlled Clinical Trial of Pembrolizumab with or without Platinum-based Combination Chemotherapy versus Chemotherapy in Subjects with Advanced or Metastatic Urothelial Carcinoma; Annex IID is updated accordingly."}, {"id":"II/0090","type":"II","opinion":"2021-01-28","decision":"2021-03-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of the currently approved therapeutic indication for the treatment of relapsed or refractory classical Hodgkin lymphoma (rrcHL) in adults to an earlier line of therapy and to include paediatric patients - as follows: KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"IAIN/0101","type":"IAIN","opinion":"2021-01-18","decision":"2021-03-09","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0091","type":"II","opinion":"2020-12-10","decision":"2021-01-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include first-line treatment of metastatic microsatellite instability-high (MSI H) or mismatch repair deficient (dMMR) colorectal cancer in adults for Keytruda based on the results from KEYNOTE-177 (an international, randomised, open-label Phase 3 trial of pembrolizumab versus chemotherapy in MSI-H or dMMR Stage IV Colorectal Carcinoma). As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, a minor correction has been made in section 4.4, “Immune related endocrinopathies” subsection. Version 29.0 of the RMP has also been submitted."}, {"id":"II/0088","type":"II","opinion":"2020-07-09","decision":"2021-01-21","affects":["SmPC"],"codes":["B.II.e.1.a.3"],"outcome":"accepted","kind":"other","sections":["6.5"],"scope":"The SmPC section 6.5 has been updated as follows: 4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl or bromobutyl stopper and an aluminium seal with a dark blue coloured flip off cap, containing 100 mg pembrolizumab."}, {"id":"II/0087/G","type":"II","opinion":"2020-07-02","decision":"2021-01-21","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final results from three interventional efficacy studies in non-small cell lung cancer; study KEYNOTE-407 listed as a PAES in the Annex II, study KEYNOTE-189 listed as a category 3 study in the RMP and KEYNOTE-021 (cohort A, C and G1) listed as a category 3 study in the RMP."}, {"id":"II/0057","type":"II","opinion":"2020-04-30","decision":"2021-01-21","affects":["SmPC","Annex II"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC to reflect the results from study KEYNOTE-042; an international, randomized, open-label Phase 3 study investigating KEYTRUDA monotherapy compared to standard of care platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1 positive (TPS ≥ 1%) NSCLC. An updated RMP version 28.0 was submitted as part of the application. In addition, the MAH revised the due date for the submission of Annex II study P361 to Q4 2020."}, {"id":"IB/0086/G","type":"IB","opinion":"2020-06-10","decision":"2021-01-21","affects":["Annex II"],"codes":["A.7","B.I.a.1.f","B.I.a.2.a","B.I.a.4.b","B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place; Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Change to in-process tests or limits applied during the manufacture of the AS - Addition of a new in-process test and limits; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IAIN/0098","type":"IAIN","opinion":"2020-12-02","decision":"2021-01-21","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0093/G","type":"IAIN","opinion":"2020-10-09","decision":"2021-01-21","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0095/G","type":"IA","opinion":"2020-11-10","decision":"2021-01-21","affects":["Annex II","PL"],"codes":["A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"PSUSA/00010403/201909","type":"PSUSA","opinion":"2020-03-26","decision":"2020-06-02","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"R/0081","type":"R","opinion":"2020-01-30","decision":"2020-03-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0080","type":"II","opinion":"2019-10-17","decision":"2019-11-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"To update sections 4.2, 4.4 and 4.8 of the SmPC on the safety information for immune-related endocrinopathies following a safety review for Addison’s disease/primary adrenal insufficiency. The updated RMP version 27.0 has also been agreed. The MAH also took the opportunity to include the changes in Annex II related to the new EMA QRD template version 10.1 and to update the details of the local representative of Portugal in the Package Leaflet."}, {"id":"II/0065","type":"II","opinion":"2019-10-17","decision":"2019-11-14","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in adults whose disease expresses PD-L1 with CPS score ≥1, based on the results from KEYNOTE-048, a randomized, multi-centre, open-label phase 3 study investigating pembrolizumab, or pembrolizumab plus platinum plus 5-FU chemotherapy versus platinum plus 5-FU plus cetuximab in subjects with first-line recurrent or metastatic HNSCC. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"IB/0079/G","type":"IB","opinion":"2019-08-22","decision":"2019-11-14","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0078/G","type":"IB","opinion":"2019-10-08","decision":"2019-11-14","affects":["Annex II"],"codes":["B.I.a.1.f","B.I.a.4.b","B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place; Change to in-process tests or limits applied during the manufacture of the AS - Addition of a new in-process test and limits; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"II/0076","type":"II","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To update section 5.1 of the SmPC based on final results from study KEYNOTE-052 (KN052) listed as a PAES in Annex II; this is a single arm Phase II Clinical Trial of pembrolizumab in subjects with advanced/unresectable or metastatic urothelial cancer (1st line)."}, {"id":"II/0075","type":"II","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect the updated results from study KEYNOTE-010 listed as a category 3 study in the RMP with a data cutoff of 16 March 2018. Study KEYNOTE-010 is a controlled phase II/III trial that randomized a total of 1034 previously-treated subjects with advanced or metastatic NSCLC whose tumours express PD-L1 to receive pembrolizumab at 2 mg/kg Q3W or 10 mg/kg Q3W or docetaxel at 75 mg/m2 Q3W. In addition, the MAH took the opportunity of this variation to include additional instructions in section 4.5 of the SmPC to clarify the use of corticosteroids in subjects treated with pembrolizumab in combination with other chemotherapeutic agents."}, {"id":"II/0074","type":"II","opinion":"2019-07-25","decision":"2019-08-26","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the CSR version 03 for study KEYNOTE-013 summarising final data from the relapsed or refractory classical Hodgkin lymphoma (r/r/cHL) cohort; the Annex II is updated with removal of the relevant obligation. The MAH also took the opportunity to introduce minor editorial changes in the SmPC."}, {"id":"II/0071","type":"II","opinion":"2019-06-27","decision":"2019-08-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"To update sections 4.2, 4.8, 5.1 and 5.2 of the SmPC based on interim results from study KEYNOTE-051; this is an ongoing Phase I/II, single-arm study to evaluate the PK, pharmacodynamics, toxicity, safety, and anti-tumour activity of pembrolizumab in paediatric participants (Measure 2 of PIP01). Additionally, the results of study Study PD018 / PA-0064; evaluation of expression of PD-1, PD-L1, and PD-L2 in archival paediatric tumour tissues, were submitted (Measure 1 of PIP01)."}, {"id":"II/0069","type":"II","opinion":"2019-07-25","decision":"2019-08-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include first line treatment of advanced or metastatic renal cell carcinoma (RCC) as combination therapy of pembrolizumab together with axitinib based on the results of the first Interim Analysis (IA1) from the pivotal study, KN426, an ongoing, Phase 3, randomized, open-label, multicenter, global study, to evaluate the efficacy and safety of pembrolizumab in combination with axitinib versus sunitinib in previously untreated subjects with advanced/metastatic RCC. It also includes supportive data from KEYNOTE-427 Cohort A (pembrolizumab monotherapy) and a Sponsored Study A4061051 (axitinib monotherapy)."}, {"id":"PSUSA/00010403/201809","type":"PSUSA","opinion":"2019-03-28","decision":"2019-05-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0062","type":"II","opinion":"2019-02-28","decision":"2019-03-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC to add an alternative dosing regimen of 400 mg every 6 weeks (Q6W) for all approved monotherapy indications and indications currently under review in addition to the currently approved 200 mg every Q3W, based on modelling and simulation analysis. No new clinical or pre-clinical studies are being submitted as part of the current application. The Package Leaflet is updated accordingly."}, {"id":"II/0060","type":"II","opinion":"2019-01-31","decision":"2019-03-11","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of metastatic squamous NSCLC in adults for Keytruda; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Additionally, editorial corrections to section 5.1 of the SmPC are introduced (concerning the procedure EMEA/H/C/003820/II/0052). The RMP version 23 has also been submitted."}, {"id":"II/0054","type":"II","opinion":"2018-11-08","decision":"2019-03-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on the final clinical study report (CSR) for KEYNOTE-045 (KN045); a phase III randomized clinical trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel or vinflunine in subjects with recurrent or progressive metastatic urothelial cancer. The submission addresses the post-authorisation measure ‘ANX 020’ and Annex IID has been updated accordingly."}, {"id":"PSUSA/00010403/201803","type":"PSUSA","opinion":"2018-10-18","decision":"2019-01-11","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0058","type":"II","opinion":"2018-10-04","decision":"2018-12-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC, to include in the existing warning regarding immune-related adverse reactions the fact that these reactions may be fatal in patients treated with pembrolizumab, as well as minor consequential amendments to increase consistency. The Package Leaflet is being updated accordingly, and for consistency with the already existing statement in the SmPC section 4.4, the Package Leaflet is also being updated to include the fact that immune-related adverse reactions can occur after discontinuation of pembrolizumab treatment. An updated RMP version 20.0 was agreed during the procedure."}, {"id":"II/0047","type":"II","opinion":"2018-10-18","decision":"2018-12-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","5.1"],"scope":"Extension of Indication to include (as monotherapy) adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection, based on study KEYNOTE-054; a randomized, double-blind, phase 3 study conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC), undertaken to evaluate adjuvant therapy with pembrolizumab compared to placebo in patients with resected high-risk melanoma (Stage IIIA [> 1 mm lymph node metastasis], IIIB and IIIC). As a consequence, sections 4.1, 4.2 and 5.1 of the SmPC have been updated and the Package Leaflet has been updated accordingly. The RMP version 22.0 was agreed."}, {"id":"IB/0055","type":"IB","opinion":"2018-08-08","decision":"2018-12-12","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0043","type":"II","opinion":"2018-07-26","decision":"2018-09-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include 1st line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC) in adults whose tumours have no EGFR or ALK positive mutations, in combination with pemetrexed and platinum chemotherapy, based on the efficacy and safety data from pivotal study KEYNOTE-189, supported by data from KEYNOTE-021 cohorts C and G. KEYNOTE-189 is a phase 3, randomized, placebo-controlled study undertaken to evaluate the efficacy and safety of pembrolizumab +pemetrexed + carboplatin or cisplatin (pembro combo) versus saline placebo + pemetrexed + carboplatin or cisplatin (control) in previously untreated subjects with advanced/metastatic nonsquamous NSCLC with no…"}, {"id":"II/0042","type":"II","opinion":"2018-07-26","decision":"2018-09-04","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include treatment as monotherapy of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy based on the results from KEYNOTE-040 (KN040) with supportive data from two additional single arm studies (KEYNOTE-012/ KEYNOTE-055). KN040 is a randomized, multi-center, pivotal phase III study investigating KEYTRUDA as a monotherapy versus standard treatment (methotrexate, docetaxel or cetuximab) in 495 patients with recurrent or metastatic HNSCC who have previously progressed on prior platinum."}, {"id":"II/0048","type":"II","opinion":"2018-06-28","decision":"2018-08-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.3"],"scope":"Update of sections 4.2, 5.1 and 5.3 of the SmPC in order to align the posology of Keytruda for the melanoma and 2nd line NSCLC indications from 2 mg/kg Q3W to a 200 mg Q3W fixed dose regimen already approved for more recent indications (1st line NSCLC, classical Hodgkin lymphoma and urothelial carcinoma) based on the available overall PK and exposure data. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the contact details of the local representative in Belgium in the Package Leaflet."}, {"id":"II/0044","type":"II","opinion":"2018-06-28","decision":"2018-08-02","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect the final overall survival efficacy data from study Keynote-024; a randomized, open-label phase III trial of pembrolizumab versus platinum based chemotherapy in 1L subjects with PD-L1 strong metastatic non-small cell lung cancer (NSCLC)."}, {"id":"II/0052","type":"II","opinion":"2018-05-31","decision":"2018-07-06","affects":["SmPC"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","5.1"],"scope":"Restriction of indication in cisplatin-ineligible urothelial carcinoma patients to exclude patients whose tumours express PD-L1 with a combined positive score (CPS) <10, based on the review of interim analysis data by the independent data monitoring committee (iDMC) from study KEYNOTE-361 listed as a PAES in the Annex II; this is a Phase III randomised, active-controlled, parallel-group, open-label trial to determine the efficacy and safety of pembrolizumab with or without chemotherapy versus chemotherapy alone as first line treatment in subjects with advanced or metastatic urothelial carcinoma. Sections 4.1, 4.2, 4.4 and 5.1 of the SmPC have been revised accordingly."}, {"id":"PSUSA/00010403/201709","type":"PSUSA","opinion":"2018-04-26","decision":"2018-06-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"T/0045","type":"T","opinion":"2018-04-16","decision":"2018-05-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0037/G","type":"II","opinion":"2018-02-22","decision":"2018-03-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of section 4.4 of the SmPC to add information regarding the risks of encephalitis, sarcoidosis and graft versus host disease (GVHD), including the occurrence of fatal GVDH events that have been reported with pembrolizumab in patients with a history of allogeneic Haematopoietic Stem Cell Transplantation (HSCT), and update of section 4.8 of the SmPC to add encephalitis as a ‘rare’ new ADR. Further, section 4.2 of the SmPC has been updated to include the recommendation to permanently discontinue pembrolizumab at the first occurrence of Grade 3 or 4 encephalitis and Grade 3 or 4 Guillain-Barré syndrome (GBS)."}, {"id":"PSUSA/00010403/201703","type":"PSUSA","opinion":"2017-10-12","decision":"2017-12-08","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0028","type":"II","opinion":"2017-07-20","decision":"2017-08-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to include the risk of myocarditis that has been reported in patients treated with pembrolizumab. The Package Leaflet has been updated accordingly. An updated RMP version 10.0 was agreed during the procedure."}, {"id":"II/0023/G","type":"II","opinion":"2017-07-20","decision":"2017-08-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Grouped application including: Extension of Indication to add treatment as monotherapy of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy based on the results from study KEYNOTE-045; a phase 3, randomized, active-controlled, multi-site, open-label trial evaluating pembrolizumab administered at 200 mg Q3W versus investigators’ choice of paclitaxel, docetaxel, or vinflunine in patients previously treated with chemotherapy."}, {"id":"IB/0033","type":"IB","opinion":"2017-06-12","decision":"2017-08-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0034","type":"IA","opinion":"2017-06-19","decision":"2017-08-24","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"II/0025","type":"II","opinion":"2017-05-18","decision":"2017-06-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC to add posology recommendations and a warning for the risk of severe skin reactions and to communicate that Stevens - Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal cases, have been reported in patients treated with pembrolizumab. The requirements for the physician educational material in Annex II and the Package Leaflet have been updated accordingly. An updated RMP version 8.2 was agreed during the procedure."}, {"id":"PSUSA/00010403/201609","type":"PSUSA","opinion":"2017-04-21","decision":"2017-06-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pembrolizumab"}, {"id":"II/0018/G","type":"II","opinion":"2017-04-21","decision":"2017-06-16","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to reflect the data from three post-authorisation efficacy studies (PAES) in melanoma, studies P001, P002 and P006; the Annex II has been revised to reflect that the relevant data have been submitted and that the Annex II conditions for the submission of the P002 and P006 CSRs, of a comparison between two dosing regimens and of biomarker analyses in the melanoma indication have been fulfilled. An updated RMP version 6.2 was agreed during the procedure."}, {"id":"IB/0024/G","type":"IB","opinion":"2017-04-20","decision":"2017-06-16","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change to an approved stability protocol"}, {"id":"II/0014","type":"II","opinion":"2017-03-23","decision":"2017-05-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to include monotherapy treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV, based on the results from study KEYNOTE-087, an open-label Phase II trial of pembrolizumab in subjects with relapsed or refractory cHL and study KEYNOTE-013, a Phase Ib multi-cohort trial of pembrolizumab in subjects with hematologic malignancies. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated and the Package Leaflet is updated accordingly."}, {"id":"II/0013","type":"II","opinion":"2017-02-02","decision":"2017-05-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","6.3","6.6"],"scope":"Update of section 4.4 of the SmPC to reflect that immune-related adverse reactions affecting more than one body system can occur simultaneously, and the fact that immune-related adverse reactions, including severe and fatal cases, have been reported in clinical trials or in post-marketing experience. In addition, the MAH took the opportunity to revise the instructions for handling and storage after reconstitution in SmPC sections 6.3 and 6.6 for increased clarity. The Package Leaflet has been updated accordingly."}, {"id":"II/0011","type":"II","opinion":"2016-12-15","decision":"2017-01-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. An updated RMP version 4.2 was agreed during the procedure."}, {"id":"X/0001/G","type":"X","opinion":"2016-06-23","decision":"2016-08-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.I.a.1.e","B.I.a.1.j","B.I.a.1.k","B.I.a.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(d) Change or addition of a new pharmaceutical form; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Replacement or addition of a site where batch control/testing takes place and any of the test method at the site is a biol/immunol method; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - New storage site of MCB and/or WCB."}, {"id":"II/0007","type":"II","opinion":"2016-06-23","decision":"2016-07-29","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","5.1","5.2","5.3","6.6"],"scope":"Extension of Indication to include a new indication for Keytruda in second line Non-Small Cell Lung Cancer (NSCLC); as a consequence, sections 4.1, 4.2, 4.4, 4.6, 4.8, 5.1, 5.2, 5.3 and 6.6 of the SmPC are updated. Annex II is updated in order to include NSCLC on-going studies among the study designed to explore value of the biomarkers to predict efficacy of pembralizumab. The Package Leaflet and the RMP (final version 3.3) is updated in accordance."}, {"id":"II/0002","type":"II","opinion":"2016-04-01","decision":"2016-07-29","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC with safety and PK data based on the CSR of Study P006v01. Further, the ADR Guillain-Barré Syndrome has been added to sections 4.4 and 4.8 of the SmPC. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to revise the text referring to fatal cases of pneumonitis in section 4.4 of the SmPC, to implement minor editorial changes in the annexes, to align the SmPC, Annex II, labelling and Package Leaflet with the latest QRD template version 9.1, and to update the contact details of the local representative in Luxemburg in the Package Leaflet. A revised RMP version 2.0 was provided as part of the application."}, {"id":"IB/0005","type":"IB","opinion":"2016-02-03","decision":"2016-07-29","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "pemigatinib__pemazyre": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/pemazyre-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"R/0019","type":"R","opinion":"2025-04-25","decision":"2025-07-02","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010923/202210","type":"PSUSA","opinion":"2023-05-25","decision":"2023-07-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pemigatinib PSUSA/10923/202210."}, {"id":"PSUSA/00010923/202204","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pemigatinib"}, {"id":"II/0005","type":"II","opinion":"2022-05-19","decision":"2023-02-23","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC based on the final results from study INCB054828 (FIGHT-202) listed as a specific obligation in the Annex II (SOB/002); this is a phase 2 study investigating the efficacy and safety of pemigatinib in adults with advanced/metastatic or surgically unresectable cholangiocarcinoma including FGFR2 translocations who failed previous therapy. The Annex II has been updated accordingly. RMP version 2.0 has also been submitted."}, {"id":"IB/0009/G","type":"IB","opinion":"2022-12-02","decision":"2023-02-23","affects":["SmPC"],"codes":["B.II.d.2.d","B.II.b.4.b","B.II.f.1.b.1","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition); Change in the batch size (including batch size ranges) of the finished product - Downscaling down to 10-fold; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"R/0003","type":"R","opinion":"2021-12-16","decision":"2022-02-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0001","type":"IB","opinion":"2021-08-03","decision":"2022-02-16","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "pertuzumab__perjeta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/perjeta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/perjeta-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000280837","type":"II","opinion":"2025-09-04","decision":"2026-03-30","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.a.1.j","B.I.a.4.a","B.I.b.2.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated as follows: Addition of Genentech, Inc., 1 Antibody Way Oceanside, CA 92056 USA as manufacturer of the biological active substance."}, {"id":"EMA/VR/0000255178","type":"II","opinion":"2025-05-08","decision":"2026-03-30","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"• The SmPC section has been updated as follows: - Sections 2 and 4.4: Reference to polysorbate 20 as excipient with known effect. - Section 6.6: alternative dilution of Perjeta concentrate with 4.5 mg/ml (0.45%) sodium chloride. • The labelling has been updated as follows: - Particulars to appear on the outer packaging – carton, section 13: ‘batch’ replaced with ‘Lot’ • The package leaflet has been updated as follows: - Reference to polysorbate 20 as excipient with known effect. - Update to contact details of local representatives"}, {"id":"EMA/VR/0000254621","type":"IA","opinion":"2025-04-03","decision":"2026-03-30","affects":["Annex II"],"codes":["A.5.b","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph."}, {"id":"EMA/VR/0000307073","type":"II","opinion":"2026-03-12","decision":null,"affects":["SmPC","Annex II","Labelling"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update safety and efficacy data, based on final results from post-authorisation efficacy study BO25126 (APHINITY) listed as a specific obligation in the Annex II; this is a phase III, randomized multicenter, double-blind, placebo-controlled comparison of chemotherapy plus trastuzumab plus placebo versus chemotherapy plus trastuzumab plus pertuzumab as adjuvant therapy in patients with operable HER2-positive primary breast cancer; the Package Leaflet and Annex II are updated accordingly. The RMP version 15.0 has also been submitted. In addition, the MAH took the opportunity to introduce editorials changes to the PI."}, {"id":"IB/0069","type":"IB","opinion":"2024-03-04","decision":null,"affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0066","type":"II","opinion":"2023-04-26","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update sections 4.8 and 5.1 to reflect updated overall survival data and cardiac safety data, based on interim results from study BO25126 (APHINITY): A randomized multicenter, double-blind, placebo-controlled comparison of chemotherapy plus trastuzumab plus placebo versus chemotherapy plus trastuzumab plus pertuzumab as adjuvant therapy in patients with operable HER2-positive primary breast cancer. In addition, the MAH took the opportunity to update the ATC code in the SmPC. Furthermore, the MAH has introduced editorial changes and updated the list of local representatives in the Package leaflet."}, {"id":"N/0057","type":"N","opinion":"2021-07-27","decision":"2022-06-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0062","type":"IB","opinion":"2021-12-09","decision":"2022-06-07","affects":["SmPC","Annex II","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IB/0056","type":"IB","opinion":"2021-04-20","decision":"2022-06-07","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0048","type":"II","opinion":"2020-04-17","decision":"2021-03-17","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.7","4.8"],"scope":"Update of section 4.8 of the SmPC in order to add safety information for elderly patients based on a safety review. Sections 4.2 and 4.4 of the SmPC and the Package leaflet have been updated accordingly. In addition, the MAH took the opportunity to make minor amendments to section 4.7 of the SmPC and to update the PL in accordance with the excipient guideline and in line with the SmPC."}, {"id":"II/0047","type":"II","opinion":"2020-04-02","decision":"2021-03-17","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to include updated OS results based on the final report from study W020698 (CLEOPATRA), a phase III, randomized, double blind, placebo-controlled clinical trial to evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel vs placebo + trastuzumab + docetaxel in previously untreated HER2-positive metastatic breast cancer."}, {"id":"PSUSA/00010125/201806","type":"PSUSA","opinion":"2019-01-31","decision":"2019-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pertuzumab"}, {"id":"II/0039","type":"II","opinion":"2018-07-05","decision":"2019-03-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC and relevant section of the PL to include tumour lysis syndrome (TLS) as a rare adverse reaction."}, {"id":"II/0034","type":"II","opinion":"2018-04-26","decision":"2018-05-31","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for Perjeta, in combination with trastuzumab and chemotherapy, for the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence. The submission is based on the primary analysis of efficacy and safety data from the pivotal Phase III study BIG-4-11/BO25126/TOC4939g (APHINITY). Sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC have been updated to reflect the study results. The Package Leaflet and RMP version 10.2 have been updated accordingly."}, {"id":"II/0035","type":"II","opinion":"2018-03-22","decision":"2018-04-30","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"An update of the posology is proposed based on an interim analysis of data from MetaPHER. This protocol-specified interim analysis was planned to evaluate the overall safety profile and tolerability of Herceptin SC in combination with Perjeta IV plus docetaxel in patients with HER2 positive advanced breast cancer (metastatic or locally recurrent). The presented data support inclusion of trastuzumab SC as an alternative to trastuzumab IV, and the safety profile of Herceptin SC+Perjeta IV+docetaxel based on the MetaPHER interim analysis seem consistent with the known safety profile of Herceptin IV+Perjeta IV+docetaxel."}, {"id":"T/0036","type":"T","opinion":"2018-02-20","decision":"2018-03-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"R/0031","type":"R","opinion":"2017-10-12","decision":"2017-12-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0029","type":"II","opinion":"2017-07-20","decision":"2017-12-08","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8, 5.1 of the SmPC, annex II and relevant sections of the PL in order to update information on cardiac safety and reflect the results from study BERENICE (WO29217) listed as a specific obligation in the Annex II.BERENICE is an ongoing Multicenter, Multinational, Phase II Study to Evaluate Perjeta in Combination with Herceptin and Standard Neoadjuvant Anthracycline-Based Chemotherapy in Patients with HER2- Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer. The MAH took the opportunity to introduce minor amendments in section 4.2. The RMP v.9 has also been updated to reflect the study results."}, {"id":"N/0024","type":"N","opinion":"2016-05-04","decision":"2016-10-27","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0026","type":"II","opinion":"2016-09-15","decision":"2016-10-27","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of study MO22324 (PHEREXA), a multicenter randomized Phase III study to compare the combination of trastuzumab and capecitabine, with or without pertuzumab, in patients with HER2-positive metastatic breast cancer that have progressed after one line of trastuzumabbased therapy in the metastatic setting. This submission fulfils the Annex II condition ANX 001 to the marketing authorisation. Annex II of the Marketing Authorisation has been updated to reflect the fulfilment of this condition. The RMP is updated to reflect the completion of the study and the MAH has taken the opportunity to include in the RMP annexes a minor amendment of the BERENICE protocol."}, {"id":"II/0021/G","type":"II","opinion":"2016-02-25","decision":"2016-10-27","affects":["Annex II"],"codes":["C.I.11.b","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of a revised RMP (version 6.0) in order to update the following information: the follow-up period of the PERUSE study is extended from 45 to 60 months. Consequently, the due date for study completion is amended to September 2020. Annex II of the Product Information is updated accordingly. Further to the outcome of the PSUSA/10125/201412 procedure and inclusion of diarrhoea management wording in the SmPC, RMP is updated to reflect this change."}, {"id":"IB/0018","type":"IB","opinion":"2015-10-22","decision":"2016-10-27","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00010125/201412","type":"PSUSA","opinion":"2015-07-23","decision":"2015-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pertuzumab"}, {"id":"II/0010","type":"II","opinion":"2015-06-25","decision":"2015-07-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include the use of pertuzumab in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence. As a consequence, update of sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 of the SmPC. In addition, the MAH took the opportunity to make a correction in sections 2 and 6.6 of the SmPC regarding the dose contained in 1 ml of solution after dilution. The Package Leaflet is updated in accordance. The requested variation proposed amendments to the SmPC, Annex II, and Package Leaflet."}, {"id":"II/0012","type":"II","opinion":"2015-03-26","decision":"2015-07-08","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC further to the final results of Study CLEOPATRA. In addition, the applicant took the opportunity to correct values in section 5.1 of the SmPC."}, {"id":"II/0009","type":"II","opinion":"2014-07-24","decision":"2015-07-08","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0007","type":"II","opinion":"2014-04-25","decision":"2014-06-30","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of section D of Annex II of the Product Information in order to amend the study protocol of MO22324 (PHEREXA) post-authorisation measure to reflect an updated statistical analysis and the deadline for fulfilment of this post-authorisation measure."}, {"id":"IB/0005","type":"IB","opinion":"2013-09-13","decision":"2014-06-30","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0003","type":"IB","opinion":"2013-06-17","decision":"2014-06-30","affects":["SmPC"],"codes":["B.II.f.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Reduction of the shelf life of the finished product - As packaged for sale"} ] }, "pertuzumab-trastuzumab__phesgo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/phesgo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/phesgo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/R/0000258704","type":"R","opinion":"2025-08-20","decision":"2025-09-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0027","type":"II","opinion":"2025-04-25","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to update administration instructions based on the final results from studies AL42478 and WP42873. AL42478 is an US expanded access, single-arm, multicentre study to provide at home subcutaneous administration of pertuzumab and trastuzumab fixed-dose combination (PH FDC SC) for patients with HER2-positive breast cancer during the COVID-19 pandemic."}, {"id":"II/0025/G","type":"II","opinion":"2024-09-05","decision":null,"affects":["Annex II"],"codes":["B.I.a.1.f","A.z","A.7","B.II.h.1.a","B.I.d.1.c","B.I.b.2.e","B.I.b.1.d","B.I.b.1.f","B.I.a.1.j","B.I.a.1.e","B.I.a.2.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Control/testing takes place and any of the test method at the site is a biol/immunol method Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product Changes in the manufacturing process of the AS - The change refers to a [-] substance in the manufacture of a biological/immunological substance which may have a…"}, {"id":"II/0023/G","type":"II","opinion":"2024-07-25","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of sections 4.8 and 11 of the SmPC in order to update the dosimetry methodology, based on results obtained with a new generation software and in accordance with the recommendations of ICRP 103, in order to fulfil a recommendation (REC)."}, {"id":"N/0018","type":"N","opinion":"2023-03-15","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0007","type":"II","opinion":"2021-09-23","decision":"2022-07-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the immunogenicity information in the section 4.8 of the SmPC based on the analysis of the Federica study (Phase III clinical trial in patients with HER2 overexpressing early breast cancer)."}, {"id":"II/0004","type":"II","opinion":"2022-01-13","decision":"2022-07-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update in Section 4.8, Undesirable Effects, to present the pooled data from Perjeta and Phesgo studies. In addition to this, the MAH has taken the opportunity to introduce minor updates in the SmPC and the Package leaflet: • Update in Section 9 of the SmPC to reflect the date of first authorisation • Editorial update in Section 4 of the the Package leaflet to add a space • Update in Section 6 of the the Package leaflet to adapt to the revised QRD Template v10.2"}, {"id":"II/0002","type":"II","opinion":"2021-06-24","decision":"2022-07-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, and 4.8, and 5.1 of the SmPC in order to support the safety of switching from intravenous to subcutaneous route of administration or vice versa, based on results from study MO40628; this is a Phase II, randomised, open-label, cross-over study to assess preference for intravenous or subcutaneous route of administration in patients with HER2-positive early breast cancer. Minor editorial changes have been introduced in the PI."} ] }, "pirtobrutinib__jaypirca": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/jaypirca-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/jaypirca-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000316267","type":"II","opinion":"2026-06-25","decision":"2026-07-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with chronic lymphocytic leukaemia (CLL) for JAYPIRCA, based on interim results from studies LOXO-BTK-20023 (BRUIN-CLL-313) and LOXO-BTK-20030 (BRUIN-CLL-314). Study 20023 is a phase 3 open-label, randomized study of pirtobrutinib (LOXO-305) versus bendamustine plus rituximab in untreated patients with CLL/SLL. Study 20030 is a phase 3 open-label, randomized study of pirtobrutinib (LOXO-305) versus ibrutinib in patients with CLL/SLL. As a consequence, sections 4.1, 4.8, 5.1, and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.1 of the RMP has also been submitted."}, {"id":"EMA/VR/0000315519","type":"IAIN","opinion":"2026-01-27","decision":"2026-07-29","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"PSUSA/00000155/202501","type":"PSUSA","opinion":"2025-09-18","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pirtobrutinib"}, {"id":"II/0002","type":"II","opinion":"2025-02-27","decision":"2025-03-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have been previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor for JAYPIRCA, based on interim results from study LOXO-BTK-20020 (BRUIN CLL-321); this is a phase 3 open-label, randomized study of LOXO-305 versus investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in BTK inhibitor pretreated CLL/SLL. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 3.1 of the RMP has also been submitted."}, {"id":"IB/0005","type":"IB","opinion":"2024-10-08","decision":"2025-03-28","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"R/0004","type":"R","opinion":"2024-06-27","decision":"2024-08-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."} ] }, "polatuzumab-vedotin__polivy": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/polivy-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/polivy-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000343429","type":"II","opinion":"2026-09-17","decision":null,"affects":["SmPC","PL"],"codes":["C.4","Q.II.b.3.z","Q.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the summary of product characteristics, labelling or package leaflet due to new quality, preclinical, clinical or pharmacovigilance data.; Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Other variation; Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"PSUSA/00010817/202506","type":"PSUSA","opinion":"2026-01-29","decision":"2026-03-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - polatuzumab vedotin"}, {"id":"EMA/VR/0000295634","type":"IB","opinion":"2025-10-16","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To remove from the Product Information the black symbol and explanatory statements for medicinal products subject to additional monitoring. Additionally, Section 5.1 of the EU SmPC is updated with information on patients with DLBCL in study GO39942 (POLARIX), which was approved for the EN SmPC with procedure EMEA/H/C/004870/II/0012, but was not yet included in the EU SmPC. Furthermore, the MAH took the opportunity to implement editorial changes throughout the PI to align with the QRD template and updated the list of local representatives in the PL."}, {"id":"II/0032/G","type":"II","opinion":"2024-10-31","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["B.I.b.2.a","B.I.b.2.e","B.II.b.3.z","B.I.c.1.c","B.I.a.1.j","B.I.a.3.c","B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Biological/immunological product"}, {"id":"N/0022","type":"N","opinion":"2023-03-10","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0012","type":"II","opinion":"2022-03-24","decision":"2022-05-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"IB/0007","type":"IB","opinion":"2021-05-05","decision":"2021-12-03","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"R/0003","type":"R","opinion":"2020-10-15","decision":"2020-12-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0002/G","type":"II","opinion":"2020-10-15","decision":"2020-12-09","affects":["SmPC","Labelling","PL"],"codes":["B.II.b.1.c","B.II.b.2.a","B.II.d.2.a","B.II.d.2.d","B.II.e.5.c","B.II.f.1.b.3","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch release/control, and secondary packaging, for biol/immunol medicinal products or pharmaceutical forms manufactured by complex manufacturing processes; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change in test procedure for the finished product - Minor changes to an approved test procedure; Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition)."} ] }, "pomalidomide__imnovid-previously-pomalidomide-celgene-": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/imnovid-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/imnovid-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/PASS/0000262876","type":"PASS","opinion":"2025-06-19","decision":null,"affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":""}, {"id":"N/0053","type":"N","opinion":"2024-12-18","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0051","type":"IB","opinion":"2023-08-25","decision":null,"affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To amend the due date for the provision of the final CSR for the EU-RMP Category 1 PASS study CC-4047-MM-015 from 31 Aug 2023 to Q1 2025."}, {"id":"II/0047","type":"II","opinion":"2023-06-08","decision":"2023-08-11","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimisation measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)- approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The updated RMP version 16.5 was provided."}, {"id":"II/0050","type":"II","opinion":"2023-07-20","decision":null,"affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update efficacy and safety information following the assessment of II/0031/G based on OS results from study CC-4047-MM-007 listed as PAES in the Annex II; this is to further investigate the efficacy of pomalidomide in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide."}, {"id":"R/0049","type":"R","opinion":"2023-02-23","decision":"2023-04-24","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IAIN/0046/G","type":"IAIN","opinion":"2021-10-27","decision":"2022-10-14","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"PSUSA/00010127/202102","type":"PSUSA","opinion":"2021-10-14","decision":"2021-12-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pomalidomide"}, {"id":"N/0043","type":"N","opinion":"2021-10-05","decision":"2021-12-09","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0045","type":"IB","opinion":"2021-10-06","decision":"2021-12-09","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IA/0044","type":"IA","opinion":"2021-08-13","decision":"2021-12-09","affects":["SmPC","Labelling"],"codes":["B.II.a.4.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in coating weight of oral dosage forms or change in weight of capsule shells - Solid oral pharmaceutical forms"}, {"id":"T/0041","type":"T","opinion":"2021-05-20","decision":"2021-06-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0038","type":"II","opinion":"2020-11-12","decision":"2021-06-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC with information from a paediatric study in patients aged 4 to 18 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma or diffuse intrinsic pontine glioma (DIPG) with primary location in the CNS."}, {"id":"IAIN/0040","type":"IAIN","opinion":"2020-11-23","decision":"2021-06-24","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0036/G","type":"II","opinion":"2020-04-30","decision":"2020-06-03","affects":["SmPC","Annex II","PL"],"codes":["C.I.z","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","6.6"],"scope":"Group of two type II variations to update sections 4.2, 4.4 and 4.8 of the SmPC and section 4 of the PL with information on anaphylactic reactions with a not known frequency and section 4.8 of SmPC with hypothyroidism following a safety review. This group also includes a Type IB Variation to update section 6.6 of the SmPC in order to include recommendations to minimise the risk of unintended occupational exposures in healthcare professionals. The MAH has also proposed minor updates to section 4.4 of the SmPC and Annex IID regarding the educational materials, prescribing and dispensing restrictions in order to provide more clarity about the recommended maximum duration of treatment."}, {"id":"II/0031/G","type":"II","opinion":"2019-03-28","decision":"2019-05-13","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.5","4.8","5.1"],"scope":"Extension of indication for Imnovid to include a new indication: treatment in combination with bortezomib and dexamethasone of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide; as a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.5, 4.8 and 5.1 of the SmPC are updated. The Annex II is also updated to include a new post-authorisation efficacy study (PAES) as an obligation of the marketing authorisation. As a further consequence, new 14-capsule pack sizes for the 1 mg, 2 mg, 3 mg and 4 mg Imnovid strengths were included to support the new proposed posology and pomalidomide dose modification."}, {"id":"IAIN/0032/G","type":"IAIN","opinion":"2018-11-19","decision":"2019-05-13","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0033","type":"IA","opinion":"2019-03-28","decision":"2019-05-13","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"T/0030","type":"T","opinion":"2018-07-13","decision":"2018-09-28","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"R/0028","type":"R","opinion":"2018-04-26","decision":"2018-07-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0027","type":"II","opinion":"2018-03-08","decision":"2018-04-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4, and 4.8 of the SmPC in order to add new ADRs SJS, TEN and DRESS following a review of reports on severe skin reactions. The Package Leaflet is updated accordingly. The RMP version 12.0 has also been submitted."}, {"id":"IAIN/0026","type":"IAIN","opinion":"2017-08-18","decision":"2018-04-23","affects":["Annex II"],"codes":["C.I.11.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of wording agreed by the competent authority"}, {"id":"IB/0022","type":"IB","opinion":"2016-09-13","decision":"2017-05-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0019","type":"IB","opinion":"2016-07-06","decision":"2017-05-24","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0018","type":"II","opinion":"2016-06-23","decision":"2016-07-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.9","5.2"],"scope":"Update of sections 4.2, 4.9 and 5.2 of the SmPC in order to update the safety information based on meta-analysis of two renal impairment studies (CC-4047-MM-008 and CC-4047-MM-013) in fulfilment of the post-authorisation measure MEA 004.1. The Package Leaflet is updated accordingly. The requested variation proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"II/0016/G","type":"II","opinion":"2016-05-26","decision":"2016-06-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.2"],"scope":"This is a grouped application of 3 Type II variations based on three clinical pharmacology study reports as follows: • Update of sections 4.2 and 5.2 of the SmPC to reflect clinical data from a hepatic impairment study (CC-4047-CP-009) on pomalidomide exposure in subjects with hepatic impairment • Update of sections 5.2 of the SmPC to reflect data from study CC-4047-CP-011 on the effect of food, smoking and elderly age on pomalidomide exposure • Update of sections 4.2, 4.5 and 5.2 of the SmPC (& PL) to reflect data from study CC-4047-CP-012 on co-administration of pomalidomide and CYP1A2 inhibitors The MAH is taking this opportunity to propose four other minor modifications to the SmPC text…"}, {"id":"PSUSA/00010127/201508","type":"PSUSA","opinion":"2016-04-01","decision":"2016-05-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pomalidomide"}, {"id":"PSUSA/00010127/201502","type":"PSUSA","opinion":"2015-09-24","decision":"2015-11-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pomalidomide"}, {"id":"PSUSA/00010127/201408","type":"PSUSA","opinion":"2015-03-26","decision":"2015-05-27","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - pomalidomide"}, {"id":"II/0005","type":"II","opinion":"2014-11-20","decision":"2015-05-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.3","6.1"],"scope":"Update of Section 4.8 of the SmPC to include the ADRs ‘pancytopenia’ and ‘tumour lysis syndrome’. The Package Leaflet is updated accordingly. In addition, editorial changes are included in Sections 4.2, 5.3, 6.1 of the SmPC and the Package Leaflet."}, {"id":"PSUV/0006","type":"PSUV","opinion":"2014-09-25","decision":"2014-11-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0003","type":"II","opinion":"2014-07-24","decision":"2014-08-26","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC following CHMP request, based on the results of population pharmacokinetics analysis to address a post authorisation measure included in the RMP."}, {"id":"IB/0007/G","type":"IB","opinion":"2014-07-28","decision":"2014-08-26","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1","B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"IAIN/0001","type":"IAIN","opinion":"2013-08-27","decision":"2014-08-26","affects":["SmPC","Labelling","PL"],"codes":["A.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the (invented) name of the medicinal product for CAPs"} ] }, "ponatinib__iclusig": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/iclusig-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/iclusig-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/X/0000296489","type":"X","opinion":"2026-05-21","decision":"2026-07-15","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication to include treatment of paediatric patients aged 6 years and older with chronic phase chronic myeloid leukaemia (CP-CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, based on interim results from study INCB 84344-102; an ongoing open-label, single-arm, Phase 1/2 study evaluating the safety and efficacy of ponatinib monotherapy for the treatment of R/R leukemias, lymphomas, or solid tumors in paediatric participants."}, {"id":"EMA/VR/0000347793","type":"IAIN","opinion":"2026-05-13","decision":"2026-07-15","affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.) - Implementation of the agreed wording"}, {"id":"IB/0072","type":"IB","opinion":"2025-02-14","decision":"2026-03-05","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"EMA/VR/0000263550","type":"II","opinion":"2026-01-29","decision":"2026-03-05","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment in combination with reduced-intensity chemotherapy of adult patients with newly-diagnosed Ph+ ALL for ICLUSIG, based on interim results from study Ponatinib-3001 (PhALLCON); this is a phase 3, randomized, open-label, multicenter study comparing ponatinib versus imatinib, administered in combination with reduced intensity chemotherapy, in patients with newly diagnosed Ph+ ALL; supportive data were derived from two single-arm, open-label clinical studies (AP24534 11 001 in combination with chemotherapy and INCB 84344-201 as monotherapy). As a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated."}, {"id":"EMA/VR/0000261199","type":"II","opinion":"2025-10-16","decision":"2026-03-05","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8, and 5.1 of the SmPC based on final results from study OPTIC (AP24534-14-203) listed as a category 3 study in the Annex II; this is a randomized, Open-label, Phase 2 Trial of Ponatinib in Patients with Resistant Chronic Phase Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses. The Package Leaflet is updated accordingly. The RMP version 23.3 has also been submitted. In addition, the MAH took the opportunity to update Annex II."}, {"id":"IA/0066","type":"IA","opinion":"2022-10-20","decision":"2023-10-12","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0061","type":"II","opinion":"2022-03-24","decision":"2022-07-08","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC based on results from the OPTIC study (AP24534-14-203) listed as a specific obligation in the Annex II. This is a randomised, open-label, Phase 2 trial of ponatinib in patients with chronic myeloid leukemia to characterise the efficacy and safety of ponatinib over a range of doses; the Package Leaflet is updated accordingly. The RMP version 21.1 has also been submitted."}, {"id":"IB/0062","type":"IB","opinion":"2021-11-23","decision":"2022-07-08","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0063","type":"IAIN","opinion":"2021-11-29","decision":"2022-07-08","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IA/0059","type":"IA","opinion":"2021-06-17","decision":"2022-07-08","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0051","type":"II","opinion":"2019-09-05","decision":"2020-07-27","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of the RMP to version 19.1, including deletion of previously agreed safety concerns; these deletions are proposed in line with the guideline on Good Pharmacovigilance Practices (GVP) Module V on RMP (revision 2 - dated on 31 March 2017)."}, {"id":"IAIN/0052","type":"IAIN","opinion":"2019-08-22","decision":"2020-07-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010128/201712","type":"PSUSA","opinion":"2018-07-26","decision":"2018-09-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ponatinib"}, {"id":"II/0045/G","type":"II","opinion":"2018-05-31","decision":"2018-09-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to reflect updated safety and efficacy information based on 64-month follow-up data from the completed study AP24534-10-201 (PACE) “ A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients with Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia”, as well as data from the final study AP24534-07-101 “A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP24534 in Patients with Refractory or Advanced Chronic Myelogenous Leukemia and other Hematologic Malignancies”. The Package Leaflet is updated accordingly."}, {"id":"T/0047","type":"T","opinion":"2018-04-25","decision":"2018-06-04","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0046","type":"IAIN","opinion":"2018-03-28","decision":"2018-06-04","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"R/0042","type":"R","opinion":"2017-12-14","decision":"2018-02-08","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0041","type":"II","opinion":"2017-12-07","decision":"2018-02-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to include a paragraph regarding severe cutaneous adverse reactions (SCARs) reported in the post-marketing setting. The Package Leaflet is updated accordingly. In addition, discrepancies between the SmPC and the Package Leaflet are being corrected in order to align the safety information in the Package Leaflet with the SmPC."}, {"id":"IB/0043/G","type":"IB","opinion":"2017-11-14","decision":"2018-02-08","affects":["Annex II","PL"],"codes":["A.5.b","A.7","B.II.b.1.a","B.II.b.1.b","B.II.b.1.e","B.II.b.2.a","B.II.b.2.c.2","B.II.b.3.a","B.II.b.4.b","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the batch size (including batch size ranges) of the finished product - Downscaling down to 10-fold Change in test procedure for the finished product - Minor changes to an approved test procedure Change in test procedure for the finished product - Minor changes to an approved test procedure Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"IB/0040","type":"IB","opinion":"2017-08-04","decision":"2018-02-08","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUSA/00010128/201612","type":"PSUSA","opinion":"2017-07-20","decision":"2017-09-21","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ponatinib"}, {"id":"II/0032/G","type":"II","opinion":"2016-12-15","decision":"2017-01-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8, 5.1 of the SmPC based on data from the ongoing Study AP24534-07-101 with a median duration of follow-up of approximately 48 months for the CP-CML patients and 3.6 months for the advanced phase Ph+ leukemia patients, as well as 48-month follow-up data from the ongoing Study AP24534-10-201 (PACE). The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor editorial changes in the SmPC and to align the annexes with the latest QRD template v.10."}, {"id":"T/0036","type":"T","opinion":"2016-10-13","decision":"2016-11-09","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Application for Transfer of Marketing Authorisation from ARIAD Pharma Ltd. to Incyte Biosciences UK Ltd. Transfer of Marketing Authorisation"}, {"id":"II/0029/G","type":"II","opinion":"2016-05-26","decision":"2016-08-25","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of section 5.3 and 4.6 of the SmPC in order to add pre-clinical information on ‘Fertility and Early Embryonic Development to Implantation’ (study 2424-001) and of section 5.3 to add pre-clincial information on ‘Carcinogenicity’ (study 805826). In addition, the Marketing authorisation holder (MAH) has submitted final study results for preclinical studies ARP590, ARP591, ARP592, ARP593, ARP593 on vascular occlusion mechanism and study ARP598 on ‘Effects of Ponatinib and its Metabolites on In Vitro Kinase Activity and Cellular Viability’ following commitments taken during Article 20 referral procedure (EMEA/H/C/002695/A-20/0003; EC decision on 15 January 2015)."}, {"id":"II/0027","type":"II","opinion":"2016-07-21","decision":"2016-08-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to include recommendations for dose modifications in case of hepatic toxicity during the treatment and to extend existing warnings and precautions for patients with severe hepatic impairment to patients with hepatic impairment of any severity. The Package Leaflet is updated accordingly. The updated RMP version 14.5 has been agreed."}, {"id":"IAIN/0034/G","type":"IAIN","opinion":"2016-06-21","decision":"2016-08-25","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0033","type":"IAIN","opinion":"2016-06-03","decision":"2016-08-25","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0031","type":"IAIN","opinion":"2016-05-11","decision":"2016-08-25","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010128/201506","type":"PSUSA","opinion":"2016-01-28","decision":"2016-03-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ponatinib"}, {"id":"II/0028","type":"II","opinion":"2016-01-28","decision":"2016-03-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to update the existing warning on vascular occlusion in relation to renal artery stenosis and to add the term as a new adverse drug reaction with frequency uncommon, accordingly. The Package Leaflet is updated accordingly. In addition, the updated RMP version 13.1 has been submitted."}, {"id":"X/0023","type":"X","opinion":"2015-09-24","decision":"2015-11-27","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"PSUSA/00010128/201412","type":"PSUSA","opinion":"2015-07-23","decision":"2015-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ponatinib"}, {"id":"II/0020","type":"II","opinion":"2015-03-26","decision":"2015-09-08","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC based on the results of study No. ARP490 (In Vitro Protein Binding of Ponatinib in Plasma from Subjects with Normal and Impaired Hepatic Function)."}, {"id":"II/0017","type":"II","opinion":"2015-03-26","decision":"2015-09-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC with further safety and efficacy information based on the updated Clinical Study report of Study AP24534-10-201 (PACE). The Package leaflet has been updated accordingly. The RMP is updated accordingly. Further, the MAH took this opportunity to update the RMP as per the requests received during the referral procedure (EMEA/H/C/002695/A-20/0003)."}, {"id":"IB/0021/G","type":"IB","opinion":"2015-05-06","decision":"2015-09-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.1.e","B.II.b.2.a","B.II.b.2.c.2","B.II.b.3.a","B.II.b.4.b","B.II.b.5.z","B.II.d.2.a","B.II.e.5.a.2","B.II.c.1.b","B.II.e.6.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"And/or limits of an excipient - Addition of a new specification parameter to the specification with its corresponding test method Change in test procedure for the finished product - Minor changes to an approved test procedure Change in any part of the (primary)"}, {"id":"IB/0016/G","type":"IB","opinion":"2015-02-02","decision":"2015-09-08","affects":["SmPC","PL"],"codes":["B.II.e.1.z","B.II.b.3.a","B.II.d.1.c","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Other variation; Change in the manufacturing process of the finished or intermediate product - Minor change in the manufacturing process; Change in the specification parameters and/or limits of the finished product - Addition of a new specification parameter to the specification with its corresponding test method; Stability of FP - Change to an approved stability protocol"}, {"id":"IAIN/0015","type":"IAIN","opinion":"2014-09-17","decision":"2015-01-15","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"A20/0003","type":"A20","opinion":"2014-10-23","decision":"2015-01-15","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Pursuant to Article 20 of Regulation (EC) No 726/2004, further to the evaluation of data relating to pharmacovigilance, the European Commission requested on 27 November 2013 the opinion of the Agency on whether the marketing authorisations of Iclusig should be maintained, varied, suspended or revoked."}, {"id":"PSUV/0009","type":"PSUV","opinion":"2014-07-24","decision":"2014-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0007","type":"II","opinion":"2014-03-20","decision":"2014-09-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to reflect the new data from study 902650 investigating the potential toxicity of ponatinib in juvenile Sprague-Dawley rats."}, {"id":"II/0005/G","type":"II","opinion":"2014-05-22","decision":"2014-09-18","affects":["SmPC","PL"],"codes":["C.I.4","C.I.11.a","C.I.11.b","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.6","5.2"],"scope":"Update of section 4.5 of the SmPC with the results of a drug-drug interaction study with rifampicin (Study AP24534-12-107); Update of sections 4.4, 4.5, 5.2 of the SmPC and the Package Leaflet with the results of a drug-drug interaction study with lansoprazole conducted as a post-authorisation measure of the RMP (Study AP24534-12-108, MEA 008); Update of sections 4.2, 4.4, 4.5 and 5.2 of the SmPC with the results of a study in patients with chronic hepatic impairment conducted as a post-authorisation measure of the RMP (Study AP24534-12- 109, MEA 001)."}, {"id":"II/0002","type":"II","opinion":"2013-11-21","decision":"2013-12-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4, 4.8 of the SmPC in order to add a warning regarding the risk of developing arterial and venous thrombotic events in patients treated with Iclusig. The Package Leaflet is updated accordingly."}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2013-08-09","decision":"2013-12-20","affects":["SmPC","Labelling","PL"],"codes":["C.I.z","A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in the name and/or address of the MAH"} ] }, "quizartinib__vanflyta": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vanflyta-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/vanflyta-epar-procedural-steps-taken-scientific-information-after-authorisation-archived_en.pdf"], "procedures": [ {"id":"EMA/VR/0000302092","type":"II","opinion":"2026-07-09","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.13","C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"A grouped application consisting of: editorial changes in the PI."}, {"id":"EMA/N/0000325243","type":"N","opinion":"2026-02-03","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives. Additionally, the MAH took the opportunity to introduce minor editorial amendments in some of the translations."}, {"id":"II/0002","type":"II","opinion":"2024-05-23","decision":"2025-04-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"To update section 4.5 and 5.2 of the SmPC in order to add information on interaction with Breast cancer resistant protein (BCRP) substrates based on results from study GE-2161 – Inhibitory Effects of Quizartinib on the Transport Activity of BCRP (REC). In addition, the MAH is taking this opportunity to introduce editorial changes to the PI."}, {"id":"IB/0005","type":"IB","opinion":"2024-12-16","decision":"2025-04-25","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0003","type":"IB","opinion":"2024-08-01","decision":"2025-04-25","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"} ] }, "radium-ra223-dichloride__xofigo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/xofigo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/xofigo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000333243","type":"II","opinion":"2026-07-23","decision":null,"affects":["Annex II"],"codes":["C.9.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of final study report from study 20511 listed in Annex IID of the SmPC. This is a phase I biodistribution study to further characterise correlation between the extent of the disease, the dose and the distribution of radium-223 in bone metastases versus sites of impaired bone health versus normal bone structure. The Annex II is updated accordingly."}, {"id":"N/0054","type":"N","opinion":"2024-07-30","decision":"2025-11-10","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0056","type":"IB","opinion":"2024-11-26","decision":"2025-11-10","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"EMA/VR/0000281776","type":"IB","opinion":"2025-07-28","decision":"2025-11-10","affects":["SmPC","Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To change the due date for the category 1 study 20510 (RADIANT) from Q4 2025 to Q2 2026, and the due date for the category 3 study 17739 (PEACE-III) from Q2 2025 to Q4 2025. The RMP and Annex II are updated accordingly. In addition, the MAH took the opportunity to implement editorial changes, including the addition of the latest renewal date in Section 9 of the SmPC, the correction of a typo in the FR PI, and implemented the switch from the Latin INN to the CZ INN throughout the CZ PI, in line with CZ pharmaceutical law update and grammar, as requested by the CZ health authority."}, {"id":"R/0049","type":"R","opinion":"2023-07-20","decision":"2023-09-15","affects":["PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0051","type":"IB","opinion":"2023-05-04","decision":"2023-09-15","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"SW/0045","type":"SW","opinion":"2021-10-14","decision":"2021-12-13","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Post Authorisation Safety Study results - EMEA/H/C/PSR/S/0034 – Variation"}, {"id":"II/0037","type":"II","opinion":"2019-10-31","decision":"2020-10-27","affects":["SmPC","PL"],"codes":["B.II.e.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in immediate packaging of the finished product - Change in type/addition of a new container - Sterile medicinal products and biological/immunological medicinal products"}, {"id":"IB/0039","type":"IB","opinion":"2020-04-24","decision":"2020-10-27","affects":["Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"A20/0028","type":"A20","opinion":"2018-07-26","decision":"2018-09-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Pursuant to Article 20 of Regulation (EC) No 726/2004, the European Commission requested on 30 November 2017 the opinion of the European Medicines Agency further to analyses of preliminary data of a clinical trial evaluating Xofigo in a patient population with asymptomatic or mildly symptomatic prostate cancer (ERA-223), found that the incidences of treatment emergent fractures and deaths were increased in the treatment arm (radium-223 dichloride plus abiraterone acetate and prednisone/prednisolone) compared to the control arm (placebo plus abiraterone acetate and prednisone/prednisolone)."}, {"id":"R/0030","type":"R","opinion":"2018-04-26","decision":"2018-06-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0025","type":"II","opinion":"2017-06-22","decision":"2017-08-14","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1, 5.2, and 11 of the SmPC based on the update of the Xofigo Company Core Data Sheet (CCDS) to version 5.0. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 10.0 and to introduce non safety related editorial changes to increase comprehensibility."}, {"id":"T/0024","type":"T","opinion":"2017-03-10","decision":"2017-04-03","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0019","type":"N","opinion":"2016-06-21","decision":"2017-04-03","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0018/G","type":"IAIN","opinion":"2016-05-30","decision":"2017-04-03","affects":["Annex II","PL"],"codes":["B.I.a.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The proposed manufacturer is part of the same pharmaceutical group as the currently approved manufacturer; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"N/0003","type":"N","opinion":"2014-04-11","decision":"2015-09-08","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0011","type":"II","opinion":"2015-07-23","decision":"2015-09-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0007","type":"II","opinion":"2015-01-22","decision":"2015-09-08","affects":["SmPC","PL"],"codes":["B.II.e.1.a.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement of the stopper material of the container closure system of Xofigo solution for injection."}, {"id":"IAIN/0006/G","type":"IAIN","opinion":"2014-09-19","decision":"2015-09-08","affects":["Annex II","PL"],"codes":["A.4","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"} ] }, "ramucirumab__cyramza": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/cyramza-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/cyramza-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000315508","type":"IAIN","opinion":"2026-01-16","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"EMA/VR/0000266389","type":"IB","opinion":"2025-06-17","decision":null,"affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To update the SmPC (sections 4.8, 5.1 and 5.2) based on the outcome of Article 46 procedure (EMEA/H/C/002829/P46) in which data available from paediatric study J1S-MC-JV01 (JV01) have been assessed. In addition, the MAH took the opportunity to conduct a few editorial changes to the Danish, Dutch, Greek and Portuguese annexes."}, {"id":"EMA/VR/0000221685","type":"II","opinion":"2024-09-19","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 5.1 and 4.8 of the SmPC in order to update overall survival information and add arterial thromboembolic event to the adverse drug reactions based on final results from study I4T-MC-JVCY; this is a Phase 3, Multi-Centre, Randomized, Double-Blind Study of Erlotinib in Combination with Ramucirumab or Placebo in Previously Untreated Patients with EGFR Mutation-Positive Metastatic Non-small Cell Lung Cancer. In addition, the MAH took the opportunity to update the PI in accordance with the latest EMA excipients guideline, and to implement editorial changes to the PI."}, {"id":"II/0053","type":"II","opinion":"2024-03-21","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update efficacy and safety data on paediatric patients following the outcome of Article 46 procedure EMEA/H/C/002829/P46/009 and based on results from study J1S-MC-JV02 (JV02). This is a randomized, open-label, phase 1/2 study evaluating ramucirumab in paediatric patients and young adults with relapsed, recurrent, or refractory synovial sarcoma. In addition, the MAH took the opportunity to implement editorial updates to the SmPC and the Package Leaflet."}, {"id":"IA/0050","type":"IA","opinion":"2022-12-12","decision":"2024-01-26","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0043","type":"II","opinion":"2022-06-23","decision":"2022-07-25","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to add a new warning on heart failure following a detailed cumulative review of post-marketing data. The Package Leaflet and Labelling are updated accordingly. In addition, the MAH took the opportunity to update the package leaflet to include hypothyroidism as a common side effect."}, {"id":"II/0039","type":"II","opinion":"2021-02-04","decision":"2022-07-18","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add hypothyroidism to the list of adverse reactions with a frequency of common based on the updated reference safety information for ramucirumab. The Package Leaflet is also updated. In addition, minor updates are included to the list of local representatives in the product information."}, {"id":"II/0038","type":"II","opinion":"2020-05-28","decision":"2022-07-18","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add posterior reversible encephalopathy syndrome (PRES) and dysphonia as a warning and as undesirable effect, respectively. The Labelling and Package Leaflet are updated accordingly. The RMP version 9.3 has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template."}, {"id":"IB/0042","type":"IB","opinion":"2021-08-21","decision":"2022-07-18","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"II/0033","type":"II","opinion":"2019-12-12","decision":"2020-01-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication for Cyramza to include in combination with erlotinib, the first-line treatment of adult patients with metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The package leaflet is updated accordingly. The RMP version 9.1 has also been agreed."}, {"id":"IAIN/0037","type":"IAIN","opinion":"2019-10-30","decision":"2020-01-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0031","type":"R","opinion":"2019-07-25","decision":"2019-09-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0030","type":"II","opinion":"2019-04-04","decision":"2019-08-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add haemangioma and thrombotic microangiopathy (TMA) as new adverse drug reactions as common and rare, respectively based on review of clinical trials, post-marketing cases and the published scientific literature. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives for Estonia, Latvia and Lithuania in the Package Leaflet."}, {"id":"II/0029","type":"II","opinion":"2019-03-14","decision":"2019-08-01","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0027","type":"II","opinion":"2019-06-27","decision":"2019-08-01","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include Cyramza as monotherapy for the treatment of adult patients with hepatocellular carcinoma who have an alpha fetoprotein (AFP) of ≥ 400 ng/mL, after prior sorafenib therapy; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated in accordance. The Package Leaflet is updated in accordance. RMP version 8.3 has been agreed."}, {"id":"II/0024/G","type":"II","opinion":"2018-09-20","decision":"2019-08-01","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.c","B.II.b.2.c.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch release/control, and secondary packaging, for biol/immunol medicinal products or pharmaceutical forms manufactured by complex manufacturing processes; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing for a biol/immunol product and any of the test methods is a biol/immunol/immunochemical method"}, {"id":"II/0023/G","type":"II","opinion":"2018-12-13","decision":"2019-08-01","affects":["Annex II"],"codes":["C.I.11.b","C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study Study I4T-MC-JVCZ (Randomized Phase 2 Trial Evaluating Alternative Ramucirumab Doses in Combination with Paclitaxel in Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma) and Study I4T-MC-JVDB (Randomized Phase 2 Trial Evaluating Pharmacokinetics and Safety of Four Ramucirumab Dosing Regimens in Second Line Gastric or Gastroesophageal Junction Adenocarcinoma); Annex II of the product information has been updated to remove study I4T-MC-JVDB."}, {"id":"N/0018","type":"N","opinion":"2017-05-17","decision":"2018-09-20","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IG/0898","type":"IG","opinion":"2018-02-12","decision":"2018-09-20","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"IB/0020","type":"IB","opinion":"2017-09-27","decision":"2018-09-20","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IG/0662","type":"IG","opinion":"2016-02-23","decision":"2017-02-17","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0004","type":"II","opinion":"2015-12-17","decision":"2016-01-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include a new indication for Cyramza, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), for the treatment of adult patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin and a fluoropyrimidine; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Furthermore, Annex II has been updated to include an obligation for the MAH to conduct a Post Authorisation Efficacy Study (PAES)."}, {"id":"II/0003","type":"II","opinion":"2015-12-17","decision":"2016-01-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of Indication to include a new indication for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with progression after platinum-based chemotherapy for CYRAMZA; as a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, one minor typographical error was corrected in section 4.2 of the SmPC. Version 6 of the Risk Management Plan was agreed."}, {"id":"II/0002/G","type":"II","opinion":"2015-09-24","decision":"2016-01-25","affects":["Annex II"],"codes":["B.I.a.2.c","B.I.a.1.e","B.I.a.3.c","B.I.a.1.j"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - The change refers to a [-] substance in the manufacture of a biological/immunological substance which may have a significant impact on the medicinal product and is not related to a protocol; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in batch size (including batch size ranges) of AS or intermediate - The change requires assessment of the comparability of a biological/immunological AS."}, {"id":"IAIN/0001","type":"IAIN","opinion":"2015-01-19","decision":"2016-01-25","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0008","type":"IA","opinion":"2015-09-16","decision":"2016-01-25","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "regorafenib__stivarga": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/stivarga-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/stivarga-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000312922","type":"II","opinion":"2026-02-26","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC in order to update paediatric information based on results from paediatric Study 7. The RMP version 7.3 has also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.4."}, {"id":"EMA/VR/0000282349","type":"IAIN","opinion":"2025-07-01","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SmPC, labelling or package leaflet of human medicinal products in order to adapt to a recommendation of a competent authority , e.g. a Core SmPC, following the assessment of an Urgent Safety Restriction etc. Implementation of wording agreed by the competent authority that require additional minor assessment, e.g. translations are not yet agreed upon."}, {"id":"N/0044","type":"N","opinion":"2024-08-29","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0039","type":"II","opinion":"2023-01-12","decision":"2024-01-05","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to remove the disease specific precaution for hepatocellular carcinoma based on final results from study REFINE (study number 19244) listed as a category 3 study in the RMP; this is an international, prospective, open-label, multi-center, observational study to describe the safety and effectiveness of treatment with regorafenib in real-world settings. The RMP version 6.1 has also been submitted"}, {"id":"IAIN/0040","type":"IAIN","opinion":"2023-03-07","decision":"2024-01-05","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL to implement the signal recommendations on 'Regorafenib – Thrombotic microangiopathy' (EPITT no: 19832), adopted at the 9-12 Jan 2023 PRAC meeting."}, {"id":"N/0037","type":"N","opinion":"2022-07-20","decision":"2022-11-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0034/G","type":"IB","opinion":"2021-12-01","decision":"2022-11-28","affects":["SmPC","Labelling","PL"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"PSUSA/00010133/202009","type":"PSUSA","opinion":"2021-06-24","decision":"2021-08-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - regorafenib"}, {"id":"IAIN/0029","type":"IAIN","opinion":"2019-09-27","decision":"2020-10-22","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0027","type":"IB","opinion":"2018-08-17","decision":"2019-08-08","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00010133/201709","type":"PSUSA","opinion":"2018-04-26","decision":"2018-06-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - regorafenib"}, {"id":"R/0025","type":"R","opinion":"2018-03-22","decision":"2018-05-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"T/0023","type":"T","opinion":"2017-06-29","decision":"2017-08-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0022/G","type":"IAIN","opinion":"2017-06-19","decision":"2017-08-07","affects":["Annex II","PL"],"codes":["A.4","A.5.a","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"II/0020","type":"II","opinion":"2017-07-04","decision":"2017-08-02","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for Stivarga to include treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the EU SmPC are updated. The package leaflet and RMP (version 5.2) have been updated accordingly. Furthermore, the PI is brought in line with the latest QRD template version 10.0."}, {"id":"PSUSA/00010133/201609","type":"PSUSA","opinion":"2017-04-21","decision":"2017-06-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - regorafenib"}, {"id":"II/0019","type":"II","opinion":"2016-12-15","decision":"2017-01-27","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"The Marketing authorisation holder (MAH) took the opportunity to update Annex II to remove condition relating to provision of data on biomarkers from the ceased COAST trial (15983). Furthermore, minor editorial changes were introduced in the Product Information. The RMP has been updated accordingly and in order to remove the safety concern in patients with severe hepatic impairment following the parallel ongoing variation EMEA/H/C/002573/II/0018."}, {"id":"II/0018","type":"II","opinion":"2016-12-15","decision":"2017-01-27","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"SmPC sections 4.2 and 5.2 are updated based on results from phase 1 study which evaluated the pharmacokinetics and safety of regorafenib in cancer subjects with severe renal impairment compared to cancer subjects without or with mild renal impairment. The package leaflet is updated accordingly."}, {"id":"II/0016","type":"II","opinion":"2016-03-17","decision":"2016-10-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC based on the final study results of Study 16674; a Phase 1 drug-drug interaction study undertaken to determine the effect of multiple doses of regorafenib on the pharmacokinetics of probe substrates of transport proteins P-gp and BCRP in patients with advanced solid malignant tumours. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make minor changes to Annex II to reflect the latest version of the QRD template (9.1), and to update the contact details of the local representative in Norway and the name of the local representative in Portugal in the Package Leaflet."}, {"id":"II/0015/G","type":"II","opinion":"2016-04-28","decision":"2016-10-14","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC based on the results from Study 15967 (CONSIGN), a Phase 3b trial in patients with metastatic colorectal cancer. In addition, the MAH took the opportunity to provide long-term results from Study 14874 (GRID addendum CSR), a pivotal phase 3 trial in patients with gastrointestinal stromal tumour (GIST). A revised RMP version 4.1 was agreed during the procedure."}, {"id":"II/0013","type":"II","opinion":"2015-11-19","decision":"2016-10-14","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"PSUSA/00010133/201503","type":"PSUSA","opinion":"2015-10-22","decision":"2015-12-16","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - regorafenib"}, {"id":"II/0014/G","type":"II","opinion":"2015-10-22","decision":"2015-12-16","affects":["SmPC","Annex II"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to delete the warning regarding patients with KRAS mutant tumours based on a biomarker report from the CONCUR (15808) study (ANX 002.4 and 002.3). In addition, the MAH has submitted the final biomarker analysis from the CORRECT trial (14387). The Annex II has been updated accordingly. Moreover, the updated RMP version 3.5 was agreed."}, {"id":"II/0008","type":"II","opinion":"2015-05-21","decision":"2015-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC in order to reflect final results from study 15808 (CONCUR; a randomized, double blind, placebo controlled phase III study of regorafenib plus best supportive care (BSC) versus placebo plus BSC in Asian subjects with metastatic CRC who have progressed after Standard therapy). The MAH took also the opportunity to introduce minor corrections and editorial changes throughout the PI. The RMP has been updated accordingly."}, {"id":"IB/0010","type":"IB","opinion":"2015-04-23","decision":"2015-12-16","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUV/0004","type":"PSUV","opinion":"2014-10-23","decision":"2014-12-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0001","type":"II","opinion":"2014-06-26","decision":"2014-07-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1","5.3"],"scope":"Extension of indication in the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib. As a consequence, sections 4.1, 4.2, 4.5, 4.8, 5.1 and 5.3 of the SmPC have been updated. The Package Leaflet has been updated accordingly. The list of local representatives was also updated in the package leaflet."}, {"id":"IB/0003/G","type":"IB","opinion":"2014-06-02","decision":"2014-07-28","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To change the due date for the submission of the biomarker data for CONCUR (study 15808) listed as condition to the Marketing Authorization in Annex II QRD, and also stated in the EU RMP part IV, 2.section Table 2-1. To extend the due date for the PAM for CONCUR (study 15808) to 31 December 2014. To extend the timelines for the primary completion of CONSIGN (15967) CSR to allow a significant follow-up time for all patients. The RMP and the Annex II are updated accordingly."} ] }, "relatlimab-nivolumab__opdualag": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/opdualag-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/opdualag-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000339077","type":"II","opinion":"2026-06-11","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to revise the wording regarding Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis; and to add ''Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis'' to the list of adverse drug reactions (ADRs) with frequency ''Uncommon'' based on postmarketing data and literature; the Package Leaflet is updated accordingly. The RMP version 6.0 has also been submitted."}, {"id":"EMA/VR/0000303785","type":"II","opinion":"2026-04-23","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 4.8 and 5.1 of the SmPC based on updated descriptive 4-year data from pivotal Study CA224047; this is a randomized, double-blind phase 2/3 study of relatlimab combined with nivolumab versus nivolumab in participants with previously untreated metastatic or unresectable melanoma. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000314728","type":"II","opinion":"2026-02-12","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome, and add Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome to the list of adverse drug reactions (ADRs) with frequency Uncommon based on postmarketing data and literature; the Package Leaflet is updated accordingly. The RMP version 5.0 has also been submitted. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"PSUSA/00011018/202403","type":"PSUSA","opinion":"2024-10-17","decision":"2024-12-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - nivolumab / relatlimab"}, {"id":"N/0004","type":"N","opinion":"2023-11-15","decision":"2024-12-12","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0010/G","type":"IAIN","opinion":"2024-06-20","decision":"2024-12-12","affects":["SmPC","PL"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "relugolix__orgovyx": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/orgovyx-epar-procedural-steps-taken-scientific-information-after-information_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/orgovyx-epar-procedural-steps-taken-scientific-information-after-information-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000378376","type":"IAIN","opinion":"2026-10-01","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.1.a","Q.II.b.2.c.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing site for part or all of the manufacturing process of the finished product (except for batch release and batch control testing sites) - Addition or replacement of a site responsible for secondary packaging; Addition or replacement of a site responsible for batch release (QP certification) - Including batch control/testing applying physicochemical and/or microbiological analytical procedures for the finished product"}, {"id":"II/0024","type":"II","opinion":"2024-10-31","decision":"2026-02-25","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to amend the frequency of an existing adverse drug reactions (ADRs) 'Myocardial infarction' from 'rare' to 'uncommon' following PSUSA 00010994/202401 procedure and based on the current available clinical trial data. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to add editorial changes."}, {"id":"EMA/VR/0000272899","type":"IB","opinion":"2025-06-13","decision":"2026-02-25","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.1.b.1","B.II.e.5.a.1","B.II.b.5.b","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in type of container or addition of a new container - Solid, semi-solid and non-sterile liquid pharmaceutical forms; Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Change to in-process tests or limits applied during the manufacture of the finished product - Addition of a new test(s) and limits; Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"EMA/VR/0000263585","type":"II","opinion":"2025-06-12","decision":"2026-02-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to clarify the co-administration of Orgovyx with apalutamide."}, {"id":"EMA/VR/0000295448","type":"IB","opinion":"2025-09-29","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","B.II.e.5.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes; Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"PSUSA/00010994/202401","type":"PSUSA","opinion":"2024-09-19","decision":"2024-11-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - relugolix PSUSA/10994/202401."}, {"id":"N/0018","type":"N","opinion":"2023-12-20","decision":"2024-11-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0020","type":"II","opinion":"2024-06-27","decision":"2024-11-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.1"],"scope":"Update of sections 4.2 and 4.5 of the SmPC to add information on “Combination with other medicines for advanced hormone-sensitive prostate cancer” based on clinical studies and literature. In addition, the MAH took the opportunity to update section 5.1 of the SmPC with 2 minor corrections."}, {"id":"PSUSA/00010994/202301","type":"PSUSA","opinion":"2023-09-14","decision":"2023-11-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - relugolix"}, {"id":"II/0012","type":"II","opinion":"2023-06-01","decision":"2023-09-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC based on final results from study MVT-601-9039; this is an In vitro Interaction Study of Relugolix with human OATP2B1 Uptake Transporter."}, {"id":"II/0009","type":"II","opinion":"2023-05-25","decision":"2023-09-15","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to include the result from study MVT-601-057. This is a Phase I, two-part, open-label, fixed (single)-sequence, two-treatment, two-period crossover study to assess the effects of relugolix on the pharmacokinetics of total dabigatran upon co-administration of relugolix and the P-gp substrate dabigatran etexilate in healthy adult men and women."}, {"id":"II/0008","type":"II","opinion":"2023-05-25","decision":"2023-09-15","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to include the result from study MVT-601-055; this is an open-label, fixed (single)-sequence crossover phase 1 study to assess the sufficiency of dose separation to mitigate absorption-mediated increases in exposure to relugolix resulting from inhibition of intestinal P-gp by azithromycin in healthy adult men."}, {"id":"IB/0011","type":"IB","opinion":"2023-03-31","decision":"2023-09-15","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Product information updated to add a new pack-size of 90 (3 packs of 30) film-coated tablets for Orgovyx 120 mg film-coated tablets (EU/1/22/1642/002)"}, {"id":"IAIN/0003/G","type":"IAIN","opinion":"2022-08-17","decision":"2023-09-15","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0002","type":"T","opinion":"2022-06-15","decision":"2022-07-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "repotrectinib__augtyro": { "source": [], "procedures": [] }, "retifanlimab__zynyz": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zynyz-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000247788","type":"II","opinion":"2026-01-29","decision":"2026-03-05","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with carboplatin and paclitaxel treatment of adult patients with metastatic or with inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC) for ZYNYZ, based on interim results from study INCMGA 0012-303 (POD1UM-303/InterAACT-2); this is a phase 3 global, multicenter, double-blind randomized study of carboplatin-paclitaxel with retifanlimab or placebo in participants with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal not previously treated with systemic chemotherapy; As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2 of the SmPC are updated."}, {"id":"EMA/PSUR/0000282291","type":"PSUSA","opinion":"2025-11-13","decision":"2026-01-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"In view of available data on immune-mediated adverse reactions in patients with pre-existing autoimmune disease from the literature and in view of a plausible mechanism of action, the PRAC considers a causal relationship between retifanlimab and in view of data on patients with pre-existing autoimmune disease, that suggest an"} ] }, "ribociclib__kisqali": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kisqali-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kisqali-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000362873","type":"IAIN","opinion":"2026-08-03","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["Q.II.e.6.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of a new pack size or change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes"}, {"id":"EMA/VR/0000325484","type":"II","opinion":"2026-07-23","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to update efficacy and safety information based on final results from Study CLEE011A3201C (RIGHT Choice). This is a randomized, open-label, Phase II prospective study investigating ribociclib + ET vs. physician choice combination chemotherapy in pre/perimenopausal patients with HR+, HER2− aBC, including investigator-assessed visceral crisis, for whom combination chemotherapy was indicated. significant improvement in PFS in the ribociclib plus NSAI arm compared to the combination chemotherapy arm (HR: 0.536, 95% CI: 0.363, 0.793 at one-sided stratified log-rank test p-value=0.000727)."}, {"id":"EMA/VR/0000315309","type":"II","opinion":"2026-03-26","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1, and 5.2 of the SmPC in order to update information on paediatric population based on the final results from the study CLEE011Q12101 listed as study 3 of the PIP EMEA-002765-PIP02-21-M01 for Kisqali; this is a Phase I/II interventional study CLEE011Q12101 designed to determine a safe dose and treatment schedule of ribociclib when combined with TOTEM, with an aim to provide a therapeutic opportunity for pediatric patients with high unmet medical need, especially those with relapsed or refractory high-risk Neuroblastoma."}, {"id":"EMA/VR/0000315465","type":"II","opinion":"2026-03-19","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to non-clinical information based on the final results from study the juvenile toxicity studies 2070096 and 2070095. Study 2070096 is listed as study 2 of the PIP EMEA-002765-PIP02-21-M01 in neuroblastoma for Kisqali."}, {"id":"PSUSA/00010633/202503","type":"PSUSA","opinion":"2025-10-16","decision":"2025-12-19","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ribociclib"}, {"id":"EMA/VR/0000323497","type":"IA","opinion":"2026-01-23","decision":"2025-12-19","affects":["Annex II","PL"],"codes":["A.5.b","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000303549","type":"IAIN","opinion":"2025-10-20","decision":"2025-12-19","affects":["SmPC"],"codes":["B.II.g.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - The implementation of the change requires no further supportive data"}, {"id":"EMA/VR/0000269890","type":"II","opinion":"2025-09-18","decision":"2025-12-19","affects":["SmPC","Labelling","PL"],"codes":["B.II.b.3.b","B.II.b.5.b","B.II.f.1.b.1","B.II.f.1.d","B.II.f.1.e","B.II.b.3.z","B.II.d.1.a","B.II.g.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Substantial changes to a manufacturing process that may have a significant impact on the quality, safety and efficacy of the medicinal product; Change to in-process tests or limits applied during the manufacture of the finished product - Addition of a new test(s) and limits; Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in the shelf-life or storage conditions of the finished product - Change in storage conditions of the finished product or the diluted/reconstituted product."}, {"id":"EMA/VR/0000261091","type":"IB","opinion":"2025-04-24","decision":"2025-12-19","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"To update section 5.1 of the SmPC by removing the words \"(excluding microscopic nodal involvement)\" since this wording inaccurately reflects the population included in the Pivotal clinical trial (Procedure No. EMEA/H/C/004213/II/0045)."} ] }, "ripretinib__qinlock": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/qinlock-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/qinlock-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000372349","type":"IB","opinion":"2026-09-17","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.1","Q.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol); Change in the shelf life or storage - Change to an approved stability protocol of the finished product"}, {"id":"EMA/VR/0000326560","type":"IAIN","opinion":"2026-02-11","decision":"2026-07-29","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"E.4 Change in the name and/or address of the marketing Term name: E.4 authorisation holder, ASMF holder, storage site of the master and/or working cell bank, manufacturing site for an active substance, intermediate or finished product, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier - E.4.a) The change in the name and/or address concerns the marketing authorisation holder."}, {"id":"EMA/VR/0000284381","type":"II","opinion":"2025-09-11","decision":"2026-07-29","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"A grouped application consisting of: Update of section 4.5 of the SmPC based on results from drug-drug interaction study DCC-2618-01-007. In addition, the MAH took the opportunity to implement editorial changes to the PI, as well as, to update the list of representatives in the Packagae Leaflet. Update of section 4.5 of the SmPC based on results from in vitro study DCC-2618-03-0046 to investigate the interaction between QINLOCK and UGT1A substrates."}, {"id":"EMA/R/0000326982","type":"R","opinion":"2026-05-21","decision":"2026-07-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"EMA/VR/0000343405","type":"II","opinion":"2026-07-09","decision":null,"affects":["SmPC","PL"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update drug interaction information based on results from study DCC-2618-01-010. This is a Phase 1 Open-label Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a Sensitive CYP3A Probe Substrate (Midazolam) in Patients with Advanced Gastrointestinal Stromal Tumor (GIST). The Package Leaflet is updated in accordance."}, {"id":"N/0017","type":"N","opinion":"2024-06-27","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0004","type":"II","opinion":"2023-01-26","decision":"2024-02-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to change posology recommendations in patients with hepatic impairment and update the description of pharmacokinetics based on final results from Study DCC-2618-01-004; a Phase 1 study of the Pharmacokinetics, Safety, and Tolerability of Ripretinib in Subjects With Hepatic Impairment Compared to Healthy Control Subjects. The Package Leaflet is updated accordingly. The RMP version 2.2 has also been submitted."}, {"id":"IB/0012","type":"IB","opinion":"2023-06-21","decision":"2024-02-08","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUSA/00010962/202205","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ripretinib"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2021-12-13","decision":"2022-12-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.5.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "rituximab__mabthera": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/mabthera-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/mabthera-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000315816","type":"II","opinion":"2026-02-12","decision":"2026-05-26","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.2"],"scope":"Update of sections 4.4, 4.8, and 5.2 of the SmPC in order to align safety information across MabThera IV and SC EU annexes based on review conducted by the Applicant. In addition, description of the pharmaceutical form and container closure system has been aligned with the currently approved module 3 sections. Also, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to bring the PI in line with the latest QRD template version."}, {"id":"EMA/VR/0000254616","type":"IA","opinion":"2025-04-29","decision":"2026-05-26","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)"}, {"id":"EMA/VR/0000254621","type":"IA","opinion":"2025-04-03","decision":null,"affects":["Annex II"],"codes":["A.5.b","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph."}, {"id":"II/0201/G","type":"II","opinion":"2024-05-16","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b","A.6"],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.3","4.8","5.1","6.2","6.4","6.5"],"scope":"Type II (C.I.3.b): Update of sections 4.1, 4.2, 4.3, 4.8, 5.1, 6.2, 6.4 and 6.5 of the SmPC in order to introduce several structural and editorial changes to align with the current SmPC guideline and to remove the educational materials for HCPs and patients, following the request by the PRAC in the AR for the PSUSA procedure EMA/PRAC/257005/2023. The Annex II, Labelling and Package Leaflet are updated accordingly. The RMP version 25.0 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and to update the list of local representatives in the Package Leaflet. Type I (A.6): To change the ATC Code of rituximab from L01XC02 to L01FA01."}, {"id":"N/0197","type":"N","opinion":"2023-03-13","decision":"2023-08-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"PSUSA/00002652/202111","type":"PSUSA","opinion":"2022-06-23","decision":"2022-08-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - rituximab"}, {"id":"II/0185/G","type":"II","opinion":"2021-07-08","decision":"2022-07-08","affects":["SmPC","PL"],"codes":["B.I.a.4.c","B.I.d.1.a.3","B.II.f.1.b.1","B.I.b.2.e","B.I.a.4.f","B.II.f.1.e","B.II.d.2.d","B.I.b.1.z","B.II.d.2.c","B.I.d.1.c","B.II.d.1.z","B.I.b.1.d"],"outcome":"accepted","kind":"other","sections":["6.3"],"scope":"As a consequence of this grouping of variations the SmPC section 6.3 Shelf-life has been updated to 3 years."}, {"id":"PSUSA/00002652/202011","type":"PSUSA","opinion":"2021-06-24","decision":"2021-08-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - rituximab"}, {"id":"IB/0181","type":"IB","opinion":"2021-02-23","decision":"2021-08-26","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0177","type":"II","opinion":"2020-09-03","decision":"2021-02-18","affects":["Annex II","Labelling","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final Clinical Study Report for study WA29330 (Pemphix) in order to fulfill the Post Authorization Measure in the Annex IID of the MabThera PI following 48 week safety follow up period of the study. In addition, the marketing authorisation holder took the opportunity to update the statement on sodium in the package leaflet and to introduce minor editorial corrections in the labelling and package leaflet."}, {"id":"II/0169","type":"II","opinion":"2020-02-27","decision":"2021-02-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of the SmPC sections 4.8, 5.1 and 5.2. with the results of the Post-authorisation efficacy study (PAES) randomised phase 3 study (PEMPHIX WA29330) which further investigated the efficacy of Mabthera in the subgroup of patients with established PV as well as characterised its long term efficacy and safety on disease progression. Annex II and PL are updated accordingly. In addition, outstanding QRD comments from EMEA/H/C/00165/II/162 are being implemented."}, {"id":"II/0168","type":"II","opinion":"2020-01-30","decision":"2020-03-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of paediatric patients (aged ≥6 months to <18 years old) with previously untreated advanced stage diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL) in combination with chemotherapy for MabThera; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 21 of the RMP has also been submitted."}, {"id":"II/0162","type":"II","opinion":"2020-01-30","decision":"2020-03-03","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include the induction of remission in paediatric patients (aged ≥ 2 to <18 years old) with severe, active granulomatosis with polyangiitis (GPA) (Wegener’s) and microscopic polyangiitis (MPA); as a consequence sections 1, 2, 4.1, 4.2, 4.4, 4.8, 5.1, 5.2, 6.5, 8 of the SmPC are updated for MabThera 100 mg and 500mg concentrate for solution for infusion. The PL was updated accordingly. In addition, the product information for the MabThera 100 mg and 500mg concentrate for solution for infusion have been combined. The RMP has been updated to version 21.1."}, {"id":"IB/0167","type":"IB","opinion":"2019-07-30","decision":"2020-03-03","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0158","type":"II","opinion":"2019-01-31","decision":"2019-03-11","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Annex II section D of the product information with removal of an obligation following the submission of the final clinical study report for study BO25341 (SAWYER, a Phase Ib adaptive, comparative, randomized, parallel-group, multi-center study of subcutaneous (SC) rituximab versus intravenous (IV) rituximab both in combination with chemotherapy (fludarabine and cyclophosphamide), in patients with previously untreated CLL). This includes reports on long-term safety in relation to body surface area (BSA) (as a measure for exposure variation) and to gender. Furthermore, the RMP version 19.1 has been agreed."}, {"id":"II/0157","type":"II","opinion":"2019-01-31","decision":"2019-03-11","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.5","5.1"],"scope":"Update of SmPC, section 5.1 and Annex II section D of the product information with removal of an obligation following the submission of the final clinical study report for study BO22334 (SABRINA, a two-stage Phase III, international, multi-centre, randomized, controlled, open-label study investigating the pharmacokinetics (PK), efficacy and safety of rituximab SC in combination with cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) chemotherapy or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy versus rituximab IV in combination with CHOP or CVP chemotherapy followed by maintenance treatment with either rituximab SC or rituximab IV)."}, {"id":"II/0150","type":"II","opinion":"2019-01-31","decision":"2019-03-11","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.8","5.1"],"scope":"Extension of indication to include the treatment of patients with moderate to severe pemphigus vulgaris (PV) for MabThera; as a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.8 and 5.1 of the SmPC are updated. The MAH provided data from a phase III, randomized, controlled, multicenter, open-label study (Study ML22196) evaluating rituximab treatment plus short-term, low dose prednisone treatment compared to long-term, standard dose prednisone treatment as first-line treatment in patients with moderate to severe pemphigus. The Package leaflet is updated accordingly. Minor corrections are also proposed for the sake of accuracy and clarity. An updated RMP (v19.1) was agreed."}, {"id":"N/0155","type":"N","opinion":"2018-08-09","decision":"2018-12-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0149","type":"II","opinion":"2018-11-15","decision":"2018-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"II/0143","type":"II","opinion":"2018-04-26","decision":"2018-12-18","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to reflect the final results of the PRIMA study (MO18264), a study in Patients with Advanced Follicular Lymphoma Evaluating the Benefit of Maintenance Therapy with Rituximab after Induction of Response with Chemotherapy plus Rituximab in Comparison with No Maintenance Therapy."}, {"id":"IB/0154","type":"IB","opinion":"2018-09-24","decision":"2018-12-18","affects":["SmPC"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"T/0148","type":"T","opinion":"2018-02-20","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0142","type":"IB","opinion":"2018-01-13","decision":"2018-03-16","affects":["SmPC"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IB/0140","type":"IB","opinion":"2017-08-04","decision":"2018-03-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IA/0136","type":"IA","opinion":"2017-06-06","decision":"2018-03-16","affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient"}, {"id":"II/0111","type":"II","opinion":"2016-06-23","decision":"2017-05-16","affects":["Annex II","Labelling"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product"}, {"id":"X/0101/G","type":"X","opinion":"2016-04-01","decision":"2016-05-26","affects":["SmPC","Labelling","PL"],"codes":["C.I.4","C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"IB/0110/G","type":"IB","opinion":"2016-02-10","decision":"2016-05-26","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0098","type":"II","opinion":"2015-01-22","decision":"2015-10-15","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","4.9","5.1"],"scope":"Update of sections 4.4, 4.8, 4.9 and 5.1 of the SmPC of the 1400 mg solution for subcutaneous injection based on the study BO22334 (“SABRINA”) in fulfilment of EU post-authorisation measures. Consequently, annex II has also been revised to remove the obligation: submission of the updated CSR of study BO22334. Minor editorial changes have been introduced throughout the PI."}, {"id":"II/0097","type":"II","opinion":"2014-09-25","decision":"2015-10-15","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0092","type":"II","opinion":"2014-04-25","decision":"2014-05-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the safety information on posterior reversible encephalopathy syndrome (PERS)."}, {"id":"II/0090","type":"II","opinion":"2014-04-25","decision":"2014-05-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to reflect the 5 year follow up results from study PRIMA in maintenance therapy for the treatment of follicular lymphoma patients responding to induction therapy, following a request from the CHMP in the context of MEA 072."}, {"id":"II/0089","type":"II","opinion":"2014-04-25","decision":"2014-05-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of sections 4.2 and 4.8 of the SmPC in order to revise the infusion rate for RA patients and update the information on infusion reactions. The Package Leaflet was updated accordingly. Amendments to the text of the patient alert card in the PL following completion of readability tests assessed as part of the follow up measure MEA071 were implemented. The updated RMP version 9.4 was also submitted."}, {"id":"X/0083","type":"X","opinion":"2014-01-23","decision":"2014-03-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(e) Change or addition of a new route of administration"}, {"id":"II/0087","type":"II","opinion":"2013-10-24","decision":"2013-11-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to strengthen the warning regarding prevention of Hepatitis B reactivation."}, {"id":"II/0085","type":"II","opinion":"2013-06-27","decision":"2013-11-20","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Implementation of change(s) requested following the assessment of an USR, class labelling, a PSUR, RMP, FUM/SO, data submitted under Article 45/46, or amendments to reflect a Core SPC - Change(s) with new additional data submitted by the MAH"}, {"id":"IA/0086","type":"IA","opinion":"2013-07-10","decision":"2013-11-20","affects":["Annex II"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0084","type":"II","opinion":"2013-03-21","decision":"2013-04-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to revise the safety information related to Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) in patients receiving MabThera. The Package Leaflet was proposed to be updated accordingly."}, {"id":"II/0080/G","type":"II","opinion":"2013-02-21","decision":"2013-04-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC with the addition of hypogammaglobulinaemia in paediatrics, addition of pneumocystis jirovecii at the request of CHMP further to the assessment of PSUR 020, inclusion of information on the duration of B-cell depletion in RA patients, amendment of a value given for the response to vaccination, rewording of the sentence referring to the occurrence of progressive multifocal leukoencephalopathy and addition of PML as “very rare”. The Package Leaflet has been updated accordingly. Furthermore, the PI has been brought in line with the latest QRD template version 8.3."}, {"id":"II/0079","type":"II","opinion":"2013-03-21","decision":"2013-04-22","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.8","5.1","5.2"],"scope":"Update of section 4.1 of the SmPC in order to extend the indication of Mabthera to include the use of Mabthera in combination with glucocorticoids for the induction of remission in adult patients with severely active Granulomatosis with polyangiitis (Wegener’s) (GPA) and Microscopic polyangiitis (MPA). SmPC sections 4.2, 4.3, 4.4, 4.8, 5.1 and 5.2 are also updated to reflect the efficacy and safety data for this indication. The Package Leaflet is updated in accordance."}, {"id":"II/0077/G","type":"II","opinion":"2012-04-19","decision":"2012-05-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","C.I.z","C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC with regard to neutropenia further to the request of the CHMP during the assessment of the last PSUR and of section 4.8 of the SmPC in order to add adverse reactions regarding hypogammaglobulinaemia. In addition, a warning in section 4.4 of the SmPC has been included in relation to traceability of the medicinal product. The Package Leaflet has been updated accordingly. Furthermore, the MAH has taken this opportunity to bring the PI in line with the latest QRD template version 8 and to update the list of local representatives in the PL."}, {"id":"II/0076/G","type":"II","opinion":"2011-11-17","decision":"2011-12-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Update of sections 4. 4, 4.8, 5.1 of the SmPC in order to provide a reanalysis of the ADRs frequency, information on the risk of prolonged B-cell depletion, information on hepatitis screening, the risk of prolonged neutropenia, warnings on cardiac events further to requests from the CHMP. The Package Leaflet has been updated accordingly. Editorial amendments were also included."}, {"id":"IB/0075","type":"IB","opinion":"2011-09-19","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Updates to SmPC and Package Leaflet regarding fatal infusion reactions occurring in Rheumatoid Arthritics patients in the postmarketing setting agreed following assessment. Furthermore, linguistic amendments have been implemented in some languages."}, {"id":"II/0072","type":"II","opinion":"2011-05-19","decision":"2011-06-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with 3-year follow-up efficacy data from the phase III study ML17102 (also know as \"CLL-8\") in patients with previously untreated chronic lymphocytic leukaemia (CLL). These follow-up data were requested by the CHMP as a follow-up measure (FUM061). Annex II has been updated to reflect the latest Risk Management Plan (RMP) version number (v. 6.0) and other minor editorial amendments have also been made in the labelling and package leaflet."}, {"id":"II/0070/G","type":"II","opinion":"2010-11-18","decision":"2010-12-20","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.a.2.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"To add a drug substance manufacturing site and to introduce changes to the manufacturing process of the active substance for harmonization across all the registered sites"}, {"id":"II/0069","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.3","4.4","4.8","4.9","5.1"],"scope":"Extension of the non-Hodgkin's lymphoma indication to include treatment of follicular lymphoma patients responding to induction therapy. As a consequence, sections 4.1, 4.2, 4.3, 4.4, 4.8, 4.9 and 5.1 of the SmPC have been updated. The Package Leaflet has been updated accordingly. Furthermore, Annex II has been updated in order to include the new version number of the Risk Management Plan (version 5.1). Minor editorial changes have also been implemented."}, {"id":"II/0065","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Section 4.1 of the SmPC has been updated to include information on improvement in physical function and reduction in the rate of joint damage as measured by x-ray, when given in combination with methotrexate. As a consequence, sections 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC have been updated. The Package Leaflet has been updated accordingly. In addition to this, sections 5.1 and 5.2 of the SmPC have been updated with additional information from studies in patients with early arthritis. Furthermore changes were made to the SmPC, labelling and Package Leaflet to bring them in line with the current QRD template. Finally Annex II has been updated in order to reflect the latest version of the RMP."}, {"id":"II/0068","type":"II","opinion":"2010-01-21","decision":"2010-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the Summary of Product Characteristics (SPC) following a review of data from post marketing experience. The Package Leaflet has been updated accordingly."}, {"id":"IA/0066","type":"IA","opinion":"2009-09-10","decision":null,"affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing site"}, {"id":"II/0064","type":"II","opinion":"2009-07-23","decision":"2009-08-21","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include MabThera in combination with chemotherapy for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukaemia (CLL). Only limited data are available on efficacy and safety for patients previously treated with monoclonal antibodies including MabThera or patients refractory to previous MabThera plus chemotherapy. Annex II has been updated to reflect the new RMP version 3.1 and other editorial amendments have also been implemented in the SPC, Labelling and Package Leaflet."}, {"id":"II/0063","type":"II","opinion":"2009-02-19","decision":"2009-03-25","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of the information on immunization data for both Non-Hodgkin's lymphoma and rheumatoid arthritis, and of the information on concomitant/ sequential use of other DMARDs under section 4.4 of the SPC. As a consequence, section 4.5 of the SPC has also been updated to reflect the rate of infections in patients receiving subsequent therapy with other DMARDs. Postmarking information has also been included in section 4.8 of the SPC under rheumatoid arthritis."}, {"id":"II/0060","type":"II","opinion":"2009-01-22","decision":"2009-02-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include MabThera in combination with chemotherapy for the first-line treatment of patients with chronic lymphocytic leukaemia."}, {"id":"II/0062","type":"II","opinion":"2008-10-23","decision":"2008-11-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"II/0059","type":"II","opinion":"2008-05-30","decision":"2008-07-04","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH applied to update the text regarding reactivation of Hepatitis B infections under Section 4.4 of the SPC; to delete non-relevant information from Section 4.5; to include safety observations from a limited number of pregnancies under section 4.6; and to include progression of Kaposi's sarcoma following treatment with MabThera + chemotherapy\"under section 4.8 of the SPC. Revisions proposed by the QRD following the procedure for the 10-year Renewal have been introduced in the SPC, Labelling, Package Leaflet and are of editorial nature."}, {"id":"R/0058","type":"R","opinion":"2008-03-19","decision":"2008-05-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0053","type":"II","opinion":"2007-12-13","decision":"2008-01-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of the first line follicular NHL indication to include all chemotherapy combinations options. Furthermore, the MAH has taken the opportunity to clarify posology and method of administration in section 4.2."}, {"id":"II/0055","type":"II","opinion":"2007-10-18","decision":"2007-11-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","5.1","5.2"],"scope":"Update of section 5.2 (Pharmacokinetic properties) of the SPC based on a population PK analysis in patients with non-Hodgkin lymphoma. Minor editorial changes are also included in sections 4.4 and 5.1 of the SPC."}, {"id":"II/0052","type":"II","opinion":"2007-07-19","decision":"2007-09-03","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"In February 2007, the CHMP requested that the European Marketing Authorisation Holder, Roche, issue a DDL across the EU concerning the two reported cases of PML. Subsequently a new case of PML in a vasculitis patient was reported and the DDL was revised and issued as of 2 April 2007. The current variation is to update section 4.4. of the SPC and also section 4 of the PIL with appropriate wording covering PML in Non-Hodgkins Lymphoma and autoimmune diseases."}, {"id":"II/0048","type":"II","opinion":"2007-02-22","decision":"2007-03-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"The MAH applied to add efficacy information to section 5.1 Pharmacodynamic Properties in the SPC, as a result of the availability of radiographic data. A minor editorial change has been introduced in the Package Leaflet to bring it in line with the latest QRD template."}, {"id":"II/0051","type":"II","opinion":"2006-12-14","decision":"2007-01-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"The MAH has applied to update section 4.8 of the SPC to include information on gastrointestinal perforation and viral infections. The Package Leaflet was updated to include the addresses of local representatives in Bulgaria and Romania."}, {"id":"IA/0049","type":"IA","opinion":"2006-10-13","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0044","type":"II","opinion":"2006-06-01","decision":"2006-07-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"The MAH applied to include maintenance therapy indicated for patients with relapsed/refractory follicular lymphoma responding to induction therapy with chemotherapy with or without MabThera."}, {"id":"II/0039","type":"II","opinion":"2006-06-01","decision":"2006-07-06","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"MabThera in combination with methotrexate is indicated for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs including one or more tumour necrosis factor (TNF) inhibitor therapies."}, {"id":"II/0043","type":"II","opinion":"2006-02-23","decision":"2006-03-20","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality changes"}, {"id":"IA/0042","type":"IA","opinion":"2005-10-14","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"IA/0036","type":"IA","opinion":"2005-04-22","decision":null,"affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing site"}, {"id":"II/0033","type":"II","opinion":"2005-01-20","decision":"2005-03-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH applied to add information on Hepatitis B reactivation (section 4.4 and 4.8 of SPC) and information on Waldenström's macroglobulinemia (section 4.8 of SPC). The Package Leaflet is updated accordingly. The MAH also took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0031","type":"II","opinion":"2004-06-23","decision":"2004-08-02","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"N/0032","type":"N","opinion":"2004-06-08","decision":null,"affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0029","type":"II","opinion":"2004-01-21","decision":"2004-03-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"II/0028","type":"II","opinion":"2004-01-21","decision":"2004-03-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"II/0025","type":"II","opinion":"2003-09-25","decision":"2004-01-14","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality changes"}, {"id":"R/0017","type":"R","opinion":"2003-04-25","decision":"2003-07-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0016","type":"II","opinion":"2002-04-25","decision":"2002-07-15","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"II/0014","type":"II","opinion":"2001-10-18","decision":"2002-03-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"I/0015","type":"I","opinion":"2001-10-22","decision":"2002-02-19","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of shelf-life as foreseen at time of authorisation"}, {"id":"N/0013","type":"N","opinion":"2001-08-10","decision":"2001-10-03","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0012","type":"II","opinion":"2001-03-01","decision":"2001-06-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"N/0008","type":"N","opinion":"2000-02-23","decision":"2000-05-03","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0005","type":"II","opinion":"1999-09-22","decision":"2000-02-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"II/0003","type":"II","opinion":"1999-05-20","decision":"1999-09-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"II/0002","type":"II","opinion":"1999-02-24","decision":"1999-06-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"} ] }, "ropeginterferon-alfa-2b__besremi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/besremi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/besremi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000334453","type":"IB","opinion":"2026-04-24","decision":null,"affects":["PL"],"codes":["Q.IV.1.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to a device co-packaged with the medicinal product or referenced in the product information - Addition or replacement of a co-packaged device or referenced device"}, {"id":"EMA/VR/0000314219","type":"IB","opinion":"2026-01-09","decision":null,"affects":["PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the 'Instructions for use' in the Package Leaflet to more precisely adapt the presentation of the dosing scheme including the 5μg increment steps, implemented in procedure EMEA/H/C/004128/II/0033/G, for the Besremi 250 μg / 0.5 mL pen presentations. In addition, The MAH took the opportunity to delete the reference to a potential pack size including six co-packed needles from English and Lithuanian 'Instructions for use' in the Package Leaflet text for the Besremi 500 μg / 0.5 mL pen. Finally, correction of a typographical error in the Norwegian 'Instructions for use' in the Package Leaflet text for the Besremi 250 μg / 0.5 mL pen was implemented."}, {"id":"EMA/VR/0000277854","type":"II","opinion":"2025-09-04","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to correct Table 1 in Section 4.8 Undesirable effects due to an error in the statistical report. In addition, the MAH took the opportunity to introduce editorial changes to the PI, and DE, DK, NL PIs."}, {"id":"IB/0039/G","type":"IB","opinion":"2025-03-29","decision":null,"affects":["SmPC","PL"],"codes":["B.II.z","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality change - Finished product - Other variation; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"EMA/VR/0000246850","type":"IB","opinion":"2025-03-29","decision":null,"affects":["PL"],"codes":["B.IV.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition or replacement of a device which is not an integrated part of the primary packaging - Device with CE marking"}, {"id":"II/0033/G","type":"II","opinion":"2024-06-27","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z","B.IV.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Change of a measuring or administration device - Addition or replacement of a device which is an integrated part of the primary packaging"}, {"id":"R/0031","type":"R","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0021","type":"II","opinion":"2022-11-17","decision":"2023-12-07","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC based on results from CONTINUATION-PV study. An open-label, multicentre, phase IIIb study assessing the long-term efficacy and safety of AOP2014 and standard first line treatment (BAT) in patients with polycythaemia vera who previously participated in the PROUDPV Study. The Package Leaflet is updated accordingly."}, {"id":"IB/0029","type":"IB","opinion":"2022-12-06","decision":"2023-12-07","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"N/0002","type":"N","opinion":"2019-12-18","decision":"2022-01-31","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0011","type":"IB","opinion":"2021-01-13","decision":"2022-01-31","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes"}, {"id":"IAIN/0019","type":"IAIN","opinion":"2021-10-01","decision":"2022-01-31","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0018/G","type":"IAIN","opinion":"2021-09-20","decision":"2022-01-31","affects":["SmPC","Labelling","PL"],"codes":["A.5.a","A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Administrative change - Change in the name and/or address of the MAH"} ] }, "rucaparib__rubraca": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/rubraca-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/rubraca-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000313308","type":"IAIN","opinion":"2025-11-27","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.e.5.a.1","B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change within the range of the currently approved pack sizes; Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product - Secondary packaging site; Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0044","type":"IAIN","opinion":"2024-04-02","decision":null,"affects":["SmPC","PL"],"codes":["C.I.12"],"outcome":"accepted","kind":"other","sections":[],"scope":"Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring"}, {"id":"IB/0042/G","type":"IB","opinion":"2024-02-14","decision":null,"affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0037","type":"II","opinion":"2023-05-25","decision":"2023-11-15","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC in order to update the efficacy and safety information based on the final results from study CO-338-014 (ARIEL 3) listed as a category 1 PAES in the Annex II; this is a phase 3, multicenter, randomized, double-blind, placebo-controlled study of rucaparib as switch maintenance following platinum-based chemotherapy in patients with platinum-sensitive, high grade serous or endometrioid epithelial ovarian, primary peritoneal or fallopian tube cancer. Annex II and the RMP version 7.1 are updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0036","type":"II","opinion":"2023-10-12","decision":"2023-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include maintenance treatment of adult patients with advanced (FIGO Stages III and IV) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy for RUBRACA, based on interim results from study CO-338-087 (ATHENA); this is a Phase III, randomised, double-blind, dual placebo controlled study of rucaparib as monotherapy and in combination with nivolumab in patients with newly diagnosed EOC, FTC, or PPC who have responded to their first-line treatment (surgery and platinum-based chemotherapy)."}, {"id":"IAIN/0041","type":"IAIN","opinion":"2023-10-10","decision":"2023-11-15","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"T/0040","type":"T","opinion":"2023-05-26","decision":"2023-06-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0038","type":"IAIN","opinion":"2022-12-07","decision":"2023-06-08","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0029","type":"II","opinion":"2022-09-15","decision":"2022-11-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"A20/0033","type":"A20","opinion":"2022-07-21","decision":"2022-09-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Pursuant to Article 20 of Regulation (EC) No 726/2004, the European Commission requested on 22 April 2022 the opinion of the European Medicines Agency to assess the impact of the results from a phase 3 study listed as a specific obligation relating to the following indication of Rubraca: ‘monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy’."}, {"id":"PSUSA/00010694/202012","type":"PSUSA","opinion":"2021-07-22","decision":"2021-09-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - rucaparib"}, {"id":"IA/0026","type":"IA","opinion":"2021-02-16","decision":"2021-09-16","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0023","type":"II","opinion":"2020-11-26","decision":"2021-03-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.6","5.2"],"scope":"Update of sections 4.5, 4.6 and 5.2 of the SmPC to add drug-drug interaction (DDI) information with rosuvastatin and oral contraceptives based on the results of Study CO-338-095 listed as a category 3 study in the RMP; Study CO-338-095 is a phase 1, open-label, DDI study to determine the effect of rucaparib on the pharmacokinetics of oral rosuvastatin (Arm A) and oral contraceptives (ethinylestradiol and levonorgestrel - Arm B) in patients with advanced solid tumours. The RMP version 6.0 has also been submitted."}, {"id":"II/0020","type":"II","opinion":"2020-11-12","decision":"2020-12-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update the information on the use of rucaparib in patients with hepatic impairment based on final results from Part I of Study CO-338-078 listed as a category 3 study in the RMP; this is a phase 1, open-label, parallel group study to determine the pharmacokinetics, safety and tolerability of rucaparib in patients with an advanced solid tumour and either moderate hepatic impairment or normal hepatic function; the Package Leaflet is updated accordingly. The RMP version 4.2 has also been submitted."}, {"id":"IB/0012","type":"IB","opinion":"2019-04-12","decision":"2020-01-27","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IAIN/0010/G","type":"IAIN","opinion":"2019-02-11","decision":"2020-01-27","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0003","type":"II","opinion":"2018-11-15","decision":"2019-01-23","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"To update section 5.2 of the SmPC based on final results from Part 1 of study CO-338-45; this is a Phase 1, single-dose study of the disposition of [14C]-radiolabelled rucaparib in patients with advanced solid tumours"}, {"id":"II/0001","type":"II","opinion":"2018-12-13","decision":"2019-01-23","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one"}, {"id":"T/0005","type":"T","opinion":"2018-11-14","decision":"2018-12-07","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "ruxolitinib__jakavi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/jakavi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/jakavi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"X/0070/G","type":"X","opinion":"2024-11-14","decision":"2025-01-13","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form; Annex I_2.(e) Change or addition of a new route of administration"}, {"id":"II/0068","type":"II","opinion":"2024-03-21","decision":"2025-01-13","affects":["SmPC","PL"],"codes":["C.I.1.c"],"outcome":"accepted","kind":"other","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add new warnings on ‘Major adverse cardiac events (MACE)’, ‘Thrombosis’, and ‘Second primary malignancies’, following an Art. 20 Class Referral involving JAK inhibitors approved to treat rheumatoid arthritis. The PIL is updated accordingly."}, {"id":"IAIN/0074/G","type":"IAIN","opinion":"2024-11-13","decision":"2025-01-13","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"II/0053","type":"II","opinion":"2022-03-24","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of patients with acute and chronic GvHD aged 12 years and older who have inadequate response to corticosteroids or other systemic therapies for Jakavi; as a consequence, sections 4.1, 4.2, 4.4, 4.8. 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 14.0 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representative for The Netherlands in the Package Leaflet."}, {"id":"IA/0058","type":"IA","opinion":"2021-08-31","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0050","type":"II","opinion":"2021-06-24","decision":"2021-07-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.1"],"scope":"Update of section 4.2 and 5.1 of the SmPC in order to update the posology and the method of administration as well as to include information on the A2201/EXPAND study CINC424A2201. The changes are based on final results of a Category 3 clinical study, phase Ib to fulfill an RMP post approval commitment. This is a dose-finding study intended to establish the maximum safe starting dose (MSSD) of ruxolitinib tablets administered orally to patients with myelofibrosis (MF) in the previous unstudied population of patients who had baseline platelet counts between ≥50×109/L and <100×109/L. The Package Leaflet is updated accordingly."}, {"id":"IB/0049","type":"IB","opinion":"2020-10-26","decision":"2021-07-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0056","type":"IAIN","opinion":"2021-06-17","decision":"2021-07-28","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010015/202002","type":"PSUSA","opinion":"2020-10-15","decision":"2020-12-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ruxolitinib"}, {"id":"II/0044","type":"II","opinion":"2020-06-11","decision":"2020-12-14","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of the SmPC sections 5.1 and 4.8 with efficacy and safety information to reflect the 5-year follow-up data from the B2301 Week 256 final clinical study report (CSR). The PL was updated accordingly. The final analyses presented in the CSR are submitted to fulfil the Post-Authorisation Measure, therefore the Annex II.D of the Product Information is updated accordingly. The changes have been reflected in the RMP version 11 submitted withe the procedure II/43. The requested variation proposed amendments to the product information, Summary of Product Characteristics and Annex II. The PL was updated accordingly."}, {"id":"II/0043","type":"II","opinion":"2020-03-12","decision":"2020-06-09","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"II/0041","type":"II","opinion":"2019-05-16","decision":"2020-06-09","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC based on the final results of a Drug-Drug Interaction (DDI) study INC4242A2106, fulfilling a Post-Authorisation Measure (MEA 0016) requested as part of a previous type II variation (Procedure No. EMEA/H/C/002464/II/0025). The study INC4242A2106 evaluated the effect of multiple doses of fluconazole on the pharmacokinetics of ruxolitinib administered as a single dose in an open-label, crossover study in healthy subjects. An updated RMP version 10 was submitted accordingly. Furthermore, the RMP template was adapted to revision 2 in line with GVP Module V Rev.2 (EMA/838713/2011 Rev 2)."}, {"id":"II/0040","type":"II","opinion":"2019-05-16","decision":"2020-06-09","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC based on final results from studies from the juvenile toxicity studies 1570143 (dose range finding juvenile study) and 157014 (juvenile development study). An updated RMP version 10 was submitted accordingly. The RMP was also updated in line with the template of the GVP Module V Rev.2 (EMA/838713/2011 Rev 2). Finally, the RMP changes requested by the PRAC in the latest PSUR (PSUSA-10015-201802) have been also implemented in this RMP. In addition, the MAH has taken the opportunity to align this RMP to the revised RMP template and to the GVP Module V Rev.2 (EMA/838713/2011 Rev 2)."}, {"id":"IAIN/0047","type":"IAIN","opinion":"2020-01-09","decision":"2020-06-09","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0035","type":"T","opinion":"2018-03-26","decision":"2018-05-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00010015/201702","type":"PSUSA","opinion":"2017-10-12","decision":"2017-12-01","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ruxolitinib"}, {"id":"R/0032","type":"R","opinion":"2017-02-23","decision":"2017-04-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0031","type":"II","opinion":"2016-12-15","decision":"2017-04-24","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update the efficacy and safety information following the completion of two 5-year follow up studies INCB 18424-351 and INC424A2352(long-term extensions of pivotal myelofibrosis studies CONFORT-I and COMFORT-II, respectively), thereby addressing one of the outstanding Obligations in Annex II. The RMP (version 7.0) has been updated with completion of post-approval commitments of studies INCB 18424-351 and CINC424A2352."}, {"id":"PSUSA/00010015/201602","type":"PSUSA","opinion":"2016-09-15","decision":"2016-11-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - ruxolitinib"}, {"id":"II/0025","type":"II","opinion":"2016-06-23","decision":"2016-07-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5"],"scope":"Update of sections 4.2 and 4.5 of the SmPC in order to include information that the concomitant use of Jakavi with fluconazole doses greater than 200 mg daily should be avoided."}, {"id":"II/0024","type":"II","opinion":"2015-10-22","decision":"2016-04-13","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a warning on reported cases of Merkell cell carcinoma in patients treated with ruxolitinib. The RMP version 6.1 has been updated accordingly."}, {"id":"IB/0028/G","type":"IB","opinion":"2016-02-23","decision":"2016-04-13","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1","B.II.e.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Change in immediate packaging of the finished product - Change in type/addition of a new container - Deletion of an immediate packaging container without a complete deletion of a strength or pharmaceutical form"}, {"id":"IB/0027","type":"IB","opinion":"2015-11-26","decision":"2016-04-13","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IAIN/0021","type":"IAIN","opinion":"2015-04-23","decision":"2016-04-13","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0018","type":"II","opinion":"2014-11-20","decision":"2015-03-11","affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC, upon request by the CHMP following assessment of LEG 011, with the ADR ‘sepsis’ and patient-year adjusted rates for sepsis from Study 251, Study 351 and Study 352."}, {"id":"II/0017/G","type":"II","opinion":"2014-11-20","decision":"2015-03-11","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Grouping of two type II variations to update sections 4.5 and 5.2 of the SmPC based on the drug-drug interaction studies CINC424A2102, undertaken to evaluate the effects of ruxolitinib on the pharmacokinetics of a monophasic oral contraceptive, and CINC424A2103, undertaken to evaluate the intestinal CYP3A4 inhibitory effect of ruxolitinib on the pharmacokinetics of orally administered midazolam. The application addresses MEA 003 and MEA 004. A revised RMP version 3.1 has been included as part of the application."}, {"id":"II/0016","type":"II","opinion":"2015-01-22","decision":"2015-03-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of Indication to add treatment of adult patients with polycythaemia vera resistant to or intolerant of hydroxyurea based on the results of Study B2301 (RESPONSE). As a result, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC have been updated and the Package Leaflet has been updated accordingly. Further, Annex II has been updated to include a new post-authorisation measure; provision of long-term efficacy and safety data from Study B2301. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC. Further, an updated RMP version 5.0 was approved as part of the application."}, {"id":"X/0013","type":"X","opinion":"2014-07-24","decision":"2014-10-03","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"To add a new strength 10 mg tablet."}, {"id":"II/0010","type":"II","opinion":"2014-07-24","decision":"2014-10-03","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0008","type":"IB","opinion":"2013-10-08","decision":"2014-10-03","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUV/0009","type":"PSUV","opinion":"2013-09-19","decision":"2013-11-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0006","type":"II","opinion":"2013-06-27","decision":"2013-11-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to include a warning on the potential risk of Progressive multifocal leukoencephalopathy (PML). The Package Leaflet was updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0005","type":"II","opinion":"2013-09-19","decision":"2013-11-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to update the dosing recommendations for patients with end-stage renal disease (ESRD) undergoing haemodialysis based on the pharmacokinetic (PK) / pharmacodynamic (PD) simulations initiated as a post-authorisation measure agreed during the initial Marketing Authorisation Application (MAA). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity of this variation to correct editorial mistakes and to update the PI in line with version 8.3 of the QRD template."}, {"id":"IB/0002/G","type":"IB","opinion":"2013-02-20","decision":"2013-11-13","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","B.II.b.1.b","B.II.b.1.a","A.7","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the number of units (e.g. tablets, ampoules, etc.) in a pack - Change outside the range of the currently approved pack sizes; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Administrative change - Deletion of manufacturing sites; Administrative change - Change in the name and/or address of a manufacturer of the finished product, including quality control sites (excluding manufacturer for batch release)"} ] }, "ruxolitinib-hemifumarate__ruxolitinib-viatris": { "source": [], "procedures": [] }, "sacituzumab-govitecan__trodelvy": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/trodelvy-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/trodelvy-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000320818","type":"II","opinion":"2026-07-23","decision":"2026-08-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for Trodelvy in combination with pembrolizumab for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumours express PD-L1 with a combined positive score (CPS) ≥ 10, based on the results from study GS-US-592-6173 (ASCENT-04), which is a phase 3 study of sacituzumab govitecan (IMMU-132) and pembrolizumab versus treatment of physician’s choice (TPC) and pembrolizumab in patients with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer, whose tumours express PD-L1."}, {"id":"EMA/R/0000326788","type":"R","opinion":"2026-05-21","decision":"2026-07-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation"}, {"id":"EMA/VR/0000312649","type":"II","opinion":"2026-05-21","decision":"2026-06-22","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication for Trodelvy as monotherapy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and who are not candidates for PD-1 or PD-L1 inhibitor therapy, based on the results from study GS-US-592-6238 (ASCENT-03), which is a phase 3 study of sacituzumab govitecan (IMMU-132) versus treatment of physician's choice (TPC) in patients with previously untreated, locally advanced, inoperable or metastatic triple-negative breast cancer whose tumours do not express PD-L1 or in patients previously treated with anti-PD-(L)1 agents in the early setting…"}, {"id":"II/0037","type":"II","opinion":"2025-04-25","decision":"2025-06-05","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","6.6"],"scope":"Update of sections 4.2 and 4.4 the SmPC in order to add information on the timing of fatal infections as well as recommendations on the use of primary prophylaxis with G-CSF in patients who are at high risk for neutropenia, based on clinical trials data, post-marketing data and the literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update section 6.6 of the SmPC to remove the requirement to calculate the required dose at the beginning of each treatment cycle or more frequently if the patient’s body weight changed by more than 10% since the previous administration as well as the requirement to warm the vials to room temperature."}, {"id":"II/0020","type":"II","opinion":"2023-06-22","decision":"2023-07-26","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting based on final results from study IMMU-132-09 (TROPiCS-02); this is an open-label, randomized, multicenter phase 3 study of sacituzumab govitecan (IMMU-132) versus treatment of physician's choice (TPC) in subjects with hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (mBC) who have failed at least two prior chemotherapy regimens. As a consequence, sections 4.1, 4."}, {"id":"II/0018/G","type":"II","opinion":"2023-01-12","decision":"2023-07-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8","5.2"],"scope":"Grouped application comprising two type II variations as follows: - To update section 4.8 of the SmPC based on an integrated summary of immunogenicity. - To update sections 4.5 and 5.2 of the SmPC based on data on the impact of concomitant medications including UGT1A1 inhibitors/inducers on SN-38 pharmacokinetic (PK) based on the PopPK model refinement."}, {"id":"PSUSA/00010959/202204","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - sacituzumab govitecan"}, {"id":"IB/0011","type":"IB","opinion":"2022-07-12","decision":"2023-02-15","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"} ] }, "selinexor__nexpovio": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/nexpovio-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/nexpovio-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000291736","type":"II","opinion":"2026-02-19","decision":"2026-03-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.2"],"scope":"A grouped application consisting of: Update of sections 4.2, and 5.2 of the SmPC in order to include the recommended dose adjustment strategy in patients with severe hepatic impairment, and update pharmacokinetic, information based on interim results from study KCP-330-027; this is an open-label, phase 1/2, interventional study assessing the effect of hepatic impairment on selinexor pharmacokinetics; the Package Leaflet is updated accordingly. The RMP version 4.0 has also been submitted. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to introduce editorial changes to the PI."}, {"id":"N/0016","type":"N","opinion":"2023-08-14","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0011","type":"II","opinion":"2023-01-26","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to add drug-drug interaction information regarding the strong CYP3A4 inhibitor, clarithromycin, based on results from the drug-drug interaction (DDI) pharmacokinetic (PK) portion of Study KCP 330-017 (STOMP) following procedure EMEA/H/C/005127/REC/003.1. This is a Phase 1b/2, multi-center, open-label, clinical study with Dose Escalation (Phase 1) and Expansion (Phase 2) to independently assess the MTD, efficacy, and safety of 10 combination therapies in 11 arms in patients with RRMM (Relapsed/Refractory Multiple Myeloma) and NDMM (Newly Diagnosed Multiple Myeloma)."}, {"id":"IAIN/0010/G","type":"IAIN","opinion":"2022-11-11","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0009/G","type":"IAIN","opinion":"2022-09-22","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0007","type":"T","opinion":"2022-06-24","decision":"2022-07-22","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0006/G","type":"IB","opinion":"2022-05-25","decision":"2022-07-22","affects":["SmPC","PL"],"codes":["B.I.d.1.a.4","B.I.b.2.z","C.I.z","B.II.f.1.b.1","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the PL to include the name and address of the site responsible for batch release of the finished period/storage period - Extension or introduction of a re-test period/storage period supported by real time data Change in test procedure for AS or starting material/reagent/intermediate - Other variation Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0001/G","type":"II","opinion":"2022-05-19","decision":"2022-07-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a","B.II.z"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","6.5"],"scope":"Extension of indication for Nexpovio in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and, • Addition of a new pack size (8 tablets) to align with the dose modification guidance for the new indication."}, {"id":"IB/0002/G","type":"IB","opinion":"2021-09-10","decision":"2022-05-13","affects":["SmPC"],"codes":["B.II.d.2.d","B.I.c.z","B.I.b.z","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition); Container closure system of the AS - Other variation; Change in control of the AS - Other variation; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "selpercatinib__retsevmo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/retsevmo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/retsevmo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000282012","type":"II","opinion":"2026-03-26","decision":"2026-06-04","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include paediatric patients 2 years and older with: (1) Advanced RET fusion-positive thyroid cancer who are radioactive iodine-refractory, (2) Advanced RET-mutant medullary thyroid cancer, (3) Advanced RET fusion-positive solid tumours, when treatment options not targeting RET provide limited clinical benefit, or have been exhausted, for RETSEVMO, based on final results from study J2G-OX-JZJJ (LOXO RET 18036, LIBRETTO-121) listed as a specific obligation in Annex II; this is a multicentre, open-label Phase 1/2 study in paediatric patients with advanced solid or primary CNS tumours harbouring an activating RET alteration."}, {"id":"EMA/VR/0000315499","type":"IAIN","opinion":"2026-02-05","decision":"2026-04-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"E.4 Change in the name and/or address of the marketing Term name: E.4 authorisation holder, ASMF holder, storage site of the master and/or working cell bank, manufacturing site for an active substance, intermediate or finished product, primary and/or secondary packaging site, manufacturer responsible for batch release, site where quality control takes place, and/or supplier of a packaging component, medical device (part), starting material, reagent and/or excipient (when mentioned in the dossier - E.4.a) The change in the name and/or address concerns the marketing authorisation holder"}, {"id":"PSUSA/00010917/202505","type":"PSUSA","opinion":"2025-12-11","decision":"2026-02-10","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - selpercatinib"}, {"id":"EMA/VR/0000247142","type":"II","opinion":"2025-04-10","decision":"2025-12-12","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update information on carcinogenesis based on results from a non-clinical 2-year carcinogenicity study of selpercatinib in rats. The RMP version 14.2 has also been submitted."}, {"id":"EMA/R/0000286890","type":"R","opinion":"2025-10-16","decision":"2025-12-12","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of conditional marketing authorisation"}, {"id":"X/0031","type":"X","opinion":"2025-02-27","decision":"2025-04-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"R/0035","type":"R","opinion":"2024-11-14","decision":"2025-01-13","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0032","type":"II","opinion":"2024-07-11","decision":"2025-01-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC based on efficacy, safety and pk information from study LIBRETTO-531 (JZJB) listed as a specific obligation in the Annex II; This study is a Phase 3 confirmatory study comparing selpercatinib to physicians’ choice of cabozantinib or vandetanib in patients with progressive advanced, kinase inhibitor naive RET-mutant medullary thyroid cancer (MTC). The Package Leaflet and Annex II are updated accordingly. The RMP version 12.1 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0030","type":"II","opinion":"2024-05-16","decision":"2025-01-13","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on ‘Epiphysiolysis of the femoral head in Paediatric Patients” and to add it to the list of adverse drug reactions (ADRs) with frequency ‘Common’, based on a safety report. The Package Leaflet is updated accordingly."}, {"id":"II/0028","type":"II","opinion":"2024-06-27","decision":"2025-01-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update efficacy and safety information based on interim results from study LIBRETTO-431 (JZJC) listed as a specific obligation in the Annex II (SOB/002); this is a randomized Phase 3 study comparing selpercatinib to platinum-based and pemetrexed therapy with or without pembrolizumab in patients with locally advanced or metastatic, RET-fusion-positive NSCLC. The Package Leaflet is updated accordingly. The variation leads to amendments to the Annex II. The RMP version 10.1 has also been agreed."}, {"id":"IB/0033","type":"IB","opinion":"2024-09-23","decision":"2025-01-13","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0022","type":"II","opinion":"2024-03-21","decision":"2024-04-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","5.1"],"scope":"Extension of indication for RETSEVMO to include the treatment of adults with advanced RET fusion positive solid tumours, when treatment options not targeting RET provide limited clinical benefit, or have been exhausted, based on interim data from study LIBRETTO-001 (LOXO-RET-17001); LIBRETTO-001 is an open-label, multicentre, global Phase 1/2 study of selpercatinib in in adult and adolescent patients with advanced RET-altered tumours. As a consequence, sections 4.1, 4.2, 4.4 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 8.1 of the RMP has been agreed. In addition, the MAH took the opportunity to implement editorial changes to the SmPC."}, {"id":"II/0021","type":"II","opinion":"2024-01-25","decision":"2024-02-29","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include the treatment of adults and adolescents 12 years and older with advanced RET fusion-positive thyroid cancer in the first-line setting for RETSEVMO based on interim data from studies LIBRETTO-001 (LOXO-RET-17001) and LIBRETTO-121; LIBRETTO-001 is an open-label, multicentre, global Phase 1/2 study of selpercatinib in patients with RET-altered advanced solid tumors. LIBRETTO-121 is a Phase 1/2 study of selpercatinib in paediatric patients with advanced RET-altered solid or primary central nervous system tumours. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"R/0026","type":"R","opinion":"2023-10-12","decision":"2024-01-05","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"PSUSA/00010917/202211","type":"PSUSA","opinion":"2023-06-22","decision":"2023-08-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - selpercatinib"}, {"id":"II/0016","type":"II","opinion":"2023-05-25","decision":"2023-06-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of section 4.8 of the SmPC in order to add chylothorax and chylous ascites to the list of adverse drug reactions (ADRs) with a “common” frequency based on a review of adverse events. In addition, the MAH took the opportunity of this variation to update the dose modification guidance for “haemorrhagic events” and ‘other adverse reactions’ in section 4.2 of the SmPC to reflect the available data. The Package Leaflet is updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2023-02-23","decision":"2023-03-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to introduce a new dose modification regimen in the event of ‘interstitial lung disease (ILD)/pneumonitis’ and to introduce it as a new warning and add it to the list of adverse drug reactions (ADRs) with frequency common, based on an internal safety review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor formatting changes to the PI."}, {"id":"II/0017","type":"II","opinion":"2022-11-10","decision":"2023-03-24","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of section 4.5 and 5.2 of the SmPC in order to reflect the final results from the drug-drug interaction (DDI) study J2G-MC-JZJV; this is a phase 1, single-center, open-label, DDI study to investigate the effect of selpercatinib on the pharmacokinetic profiles of dabigatran, a P-glycoprotein (P-gp) substrate, in healthy volunteers. The Package Leaflet is updated accordingly."}, {"id":"II/0014/G","type":"II","opinion":"2022-07-21","decision":"2022-09-02","affects":["SmPC","PL"],"codes":["C.I.6.a","C.I.z"],"outcome":"accepted","kind":"indication","sections":["4.1","5.1"],"scope":"Extension of indication to include first-line treatment of advanced RET-mutant medullary thyroid cancer (MTC) in adults and adolescents 12 years and older based on interim results from Study LIBRETTO-001 (LOXO-RET-17001) on the clinical safety and efficacy of selpercatinib in patients with RET-mutant MTC who are cabozantinib and vandetanib treatment-naïve (MTC:-Cab/-Van). LIBRETTO-001 is a global, multicohort, open-label, Phase 1/2 study in adult and adolescent patients with advanced RET-altered tumours. As a consequence, sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 3.0 of the RMP has also been submitted."}, {"id":"II/0011","type":"II","opinion":"2022-04-22","decision":"2022-06-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.8","5.1"],"scope":"Extension of indication to include the first-line treatment of RET fusion-positive NSCLC for Retsevmo based on results from study LIBRETTO-001, an open-label, multicentre, global Phase 1/2 study of selpercatinib in patients with RET-altered advanced solid tumours; as a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. In addition, section 5.1 of the SmPC is revised to reflect updated efficacy data in previously treated RET-fusion positive NSCLC based on a data cut-off of 15 June 2021. The Package Leaflet is updated in accordance. Version 1.3 of the RMP has also been submitted."}, {"id":"II/0010","type":"II","opinion":"2022-04-22","decision":"2022-06-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"PSUSA/00010917/202105","type":"PSUSA","opinion":"2021-12-16","decision":"2022-02-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - selpercatinib"}, {"id":"R/0008","type":"R","opinion":"2021-10-14","decision":"2021-12-16","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0001","type":"N","opinion":"2021-04-06","decision":"2021-12-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0003/G","type":"IB","opinion":"2021-06-22","decision":"2021-12-16","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.a.2","B.II.e.5.a.1","B.II.d.2.d","B.II.e.1.b.1","B.II.b.1.b","B.II.b.1.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site Administrative change - Deletion of manufacturing sites"} ] }, "selumetinib__koselugo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/koselugo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/koselugo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000347385","type":"II","opinion":"2026-09-03","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"A grouped application consisting of: Update of sections 4.4, and 4.8 of the SmPC in order to include revised information on the retinal disorders based on review of all available safety data. The RMP version 5.2 has also been submitted to align the RMP with the current safety evidence, clarifying the relative clinical significance of retinal events, and support pharmacovigilance activities for ocular disorders in NF1-PN Update of sections 4.4, and 4.8 of the SmPC in order to revise time-to-onset data following correction of programming error in the KOMET study, describing the median time to onset at maximum Common Terminology Criteria for Adverse Event (CTCAE) grade."}, {"id":"X/0018/G","type":"X","opinion":"2025-11-13","decision":"2026-01-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2"],"scope":"Extension application to introduce a new pharmaceutical form (Granules in capsules for opening) associated with new strengths (5 mg and 7.5 mg capsule) grouped with a Type II variation (C.I.4) to update sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC of Koselugo Capsules in order to align with the SmPC of Koselugo granules in capsules for opening. The Package Leaflet and Labelling are updated accordingly. The new presentations are indicated for the treatment of symptomatic, inoperable plexiform neurofibromas in patients with neurofibromatosis type 1 aged 1 year to less than 7 years and for older patients with swallowing difficulties."}, {"id":"EMA/VR/0000245231","type":"II","opinion":"2025-09-18","decision":"2025-10-24","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication for KOSELUGO to include treatment of adults based on results from study D134BC00001 (KOMET). This is a phase III, multicentre, international study with a parallel, randomised, double-blind, placebo-controlled, 2 arm design that assesses efficacy and safety of selumetinib in adult participants with NF1 who have Symptomatic Inoperable Plexiform Neurofibromas. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.1 of the RMP has also been agreed. In addition, the Marketing authorisation holder (MAH) took the opportunity to implement editorial changes to the SmPC."}, {"id":"II/0013","type":"II","opinion":"2023-09-14","decision":"2023-10-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to update the recommended dosage regimen to remove the fasting state and update pharmacokinetic information, based on the final results from study D1346C00015; this is a phase 1, single-arm, sequential study to evaluate the effect of food on the gastrointestinal tolerability and pharmacokinetics of selumetinib after multiple doses in adolescent children with neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PN). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"R/0010","type":"R","opinion":"2023-03-30","decision":"2023-05-31","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0012","type":"N","opinion":"2023-01-13","decision":"2023-05-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0008","type":"N","opinion":"2022-07-18","decision":"2023-05-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0005","type":"N","opinion":"2022-06-29","decision":"2023-05-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"R/0003","type":"R","opinion":"2022-02-24","decision":"2022-04-25","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0002","type":"IB","opinion":"2021-10-19","decision":"2022-04-25","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"} ] }, "serplulimab__hetronifly": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/hetronifly-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/N/0000379488","type":"N","opinion":"2026-10-08","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with the addition of contact details of local representatives."}, {"id":"EMA/VR/0000290021","type":"II","opinion":"2026-05-21","decision":"2026-06-19","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include HETRONIFLY in combination with carboplatin and nab-paclitaxel for the first-line treatment of adult patients with unresectable, locally advanced or metastatic squamous non-small cell lung carcinoma based on final results from study HLX10-004-NSCLC303; this is a randomized, double-blind, multi-center, phase III pivotal study, to compare the clinical efficacy and safety of serplulimab combined with chemotherapy (carboplatin and nab-paclitaxel) versus placebo combined with chemotherapy (carboplatin and nab-paclitaxel). As a consequence, sections 4.1, 4.2, 4.8, 5.1, 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000291455","type":"II","opinion":"2025-12-04","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of SmPC in order to include myasthenia gravis and myasthenic syndrome to the list of adverse drug reactions (ADRs) with frequency “rare”, based on a signal assessment report. Additional warning and recommendations for treatment modifications are also included. The Package Leaflet is updated accordingly. The updated RMP version 1.4 has also been submitted."}, {"id":"EMA/VR/0000284402","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include, in combination with fluoropyrimidine- and platinum-based chemotherapy, the first-line treatment of adult patients with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma whose tumours express PD-L1 with a CPS ≥ 5 for HETRONIFLY, based on results from study HLX10-007-EC301; this is a randomized, double-blind, multi-center, phase III clinical study comparing the clinical efficacy and safety of HLX10 or placebo combined with chemotherapy in first-line treatment of locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) patients."}, {"id":"EMA/VR/0000282407","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2"],"scope":"Extension of indication to include HETRONIFLY in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung carcinoma who do not have EGFR or ALK positive mutations based on results from study HLX10-002-NSCLC301. As a consequence, sections 4.1, 4.2, 4,4, 4.8, 5.1, 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 2.0 of the RMP has also been approved."}, {"id":"EMA/VR/0000272312","type":"IB","opinion":"2025-07-25","decision":"2026-04-30","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","5.2","5.3","6.1"],"scope":"To update section 2 of the SmPC and section 2 of the package leaflet to include polysorbate 80 as an excipient as per the Excipients Guideline. - To update sections 4.2, 4.4, 4.5, 4.8, 5.2, 5.3 and 6.1 of the SmPC, annex IID, and section 4 of the package leaflet in order to implement changes proposed by member states Spain and Germany as part of the post-opinion linguistic review of the MAA application. - In addition, the MAH has taken the opportunity to update Part B of Annex II to revise the legal status of Hetronifly from \"special and restricted medical prescription\" to \"restricted medical prescription\" in order to align the PI with the RMP."}, {"id":"EMA/VR/0000266638","type":"IAIN","opinion":"2025-05-05","decision":"2026-04-30","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation"}, {"id":"EMA/T/0000252778","type":"T","opinion":"2025-02-26","decision":"2025-03-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from Henlius Europe GmbH to Accord Healthcare S.L.U."} ] }, "sonidegib__odomzo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/odomzo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/odomzo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000268112","type":"II","opinion":"2025-10-02","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.3","6.6"],"scope":"Update of sections 5.3, and 6.6 of the SmPC in order to update non-clinical safety information on carcinogenicity based on final results from studies 8371102, and BRT_17_037G_TN; this is a 26-Week Oral Gavage Carcinogenicity Study with LDE225 in Transgenic Mice (RasH2 [001178-T (hemizigous), CByB6F1-Tg(HRAS)2Jic]), and a 104-Week Carcinogenicity Study of LDE225 in Wistar Rats by Oral Route, respectively. Sections 5.3 and 6.6 of the SmPC were also updated to include a statement on risk to the environment in line with the commitment following EMEA/H/C/002839/IB/0056. The RMP version 8.1 has also been submitted."}, {"id":"IA/0037","type":"IA","opinion":"2021-04-07","decision":null,"affects":["SmPC","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0032","type":"N","opinion":"2020-09-30","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"R/0028","type":"R","opinion":"2020-03-26","decision":"2020-05-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0025","type":"N","opinion":"2019-08-08","decision":"2019-10-04","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0021","type":"IB","opinion":"2018-10-02","decision":"2019-10-04","affects":["SmPC","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0016","type":"II","opinion":"2018-01-25","decision":"2018-05-08","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment is required"}, {"id":"II/0011","type":"II","opinion":"2017-07-06","decision":"2018-05-08","affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority"}, {"id":"II/0010","type":"II","opinion":"2017-06-01","decision":"2018-05-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"IB/0017","type":"IB","opinion":"2017-12-15","decision":"2018-05-08","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"T/0012","type":"T","opinion":"2017-03-31","decision":"2017-05-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0008/G","type":"II","opinion":"2017-01-26","decision":"2017-05-31","affects":["SmPC"],"codes":["C.I.13","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0005","type":"II","opinion":"2016-11-10","decision":"2017-05-31","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"To resolve two post-authorisation measures (Post Authorisation Efficacy Studies) listed in the Annex II.D of the Marketing Authorisation, resulting in an update of the sections 4.8 and 5.1 of the SmPC, the Annex II and RMP."}, {"id":"II/0001/G","type":"II","opinion":"2016-01-28","decision":"2016-02-24","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC to add information on posology and pharmacology of sonidegib in hepatic impaired patients based on results from study CLDE225A2113 (MEA 006) and update of section 4.5 of the SmPC to add information on Drug-Drug interaction with proton pump inhibitors (esomeprazole) based on results from study CLDE225A2118 (MEA 007). The Risk Management Plan of the product has been updated accordingly and the final version approved is 3.1."} ] }, "sorafenib__nexavar": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/nexavar-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"II/0059","type":"II","opinion":"2025-02-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to update preclinical safety data on carcinogenicity studies based on final results from studies T4079666 - Carcinogenicity Study in CD-1 Mice (2 Years Administration by Diet) and T8076320 - Carcinogenicity Study in Wistar Rats (2 Years Administration in the Diet with Dose Adjustment). The RMP has been updated with the result of these studies; RMP version 13.1 is acceptable. In addition, the MAH took the opportunity to introduce editorial changes to the PI and to update the list of local representatives in the Package Leaflet."}, {"id":"IB/0060/G","type":"IB","opinion":"2024-06-24","decision":"2024-07-24","affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change to an approved stability protocol"}, {"id":"IB/0058/G","type":"IB","opinion":"2023-07-06","decision":"2024-07-24","affects":["SmPC","PL"],"codes":["B.II.b.4.a","A.7","B.II.b.2.a","B.II.b.1.e","B.II.b.3.a","B.II.a.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the batch size (including batch size ranges) of the finished product - Up to 10-fold compared to the originally approved batch size; Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products."}, {"id":"IAIN/0056","type":"IAIN","opinion":"2022-05-09","decision":"2023-05-15","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL to implement the signal recommendations on ‘Sorafenib – Tumour lysis syndrome’ (EPITT no 19733), adopted at the 7-10 February 2022 PRAC meeting."}, {"id":"IA/0057","type":"IA","opinion":"2022-10-19","decision":"2023-05-15","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"N/0055","type":"N","opinion":"2021-12-02","decision":"2022-03-28","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0054","type":"IA","opinion":"2021-03-23","decision":"2022-03-28","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IAIN/0051","type":"IAIN","opinion":"2019-10-04","decision":"2020-10-09","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"N/0044","type":"N","opinion":"2017-09-06","decision":"2019-06-06","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0046","type":"IB","opinion":"2018-06-25","decision":"2019-06-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"T/0042","type":"T","opinion":"2017-06-12","decision":"2017-07-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0038","type":"N","opinion":"2016-09-02","decision":"2017-07-06","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0039/G","type":"IAIN","opinion":"2017-03-16","decision":"2017-07-06","affects":["Annex II","PL"],"codes":["A.4","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"PSUV/0037","type":"PSUV","opinion":"2014-09-25","decision":"2014-11-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update"}, {"id":"II/0035","type":"II","opinion":"2014-04-25","decision":"2014-05-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3","6.6"],"scope":"Extension of the indication for the treatment of progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma, refractory to radioactive iodine. The SmPC was revised in order to add warnings on the risk of bleeding, hypocalcaemia and TSH suppression as well as reflect relevant non-clinical and clinical safety and efficacy data in patients with differentiated thyroid carcinoma. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2, 5.3 and 6.6 of the SmPC have been updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"N/0036","type":"N","opinion":"2014-01-17","decision":"2014-01-31","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0034/G","type":"II","opinion":"2013-02-21","decision":"2014-01-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 of the SmPC to delete the warning on limited experience with the use of Nexavar in elderly, and update of section 4.8 of the SmPC to add hypokalaemia, proteinuria and nephrotic syndrome as new adverse reactions and include updated information on interstitial lung like events based on the results of a safety review. The Package Leaflet is updated accordingly. Furthermore, Annex II is being brought in line with the latest QRD template version 8.3."}, {"id":"II/0032","type":"II","opinion":"2012-05-24","decision":"2012-06-27","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8"],"scope":"Update of SmPC section 4.8 and PL regarding the adverse reactions hypocalcaemia and toxic epidermal necrolysis as well as a change of SmPC section 4.5 regarding interaction with carboplatin based on already assessed data with II/18G. The MAH also took the opportunity to update the PI in accordance with QRD version 8 rev 1 including corrections to the List of Local Representatives."}, {"id":"IB/0031/G","type":"IB","opinion":"2012-01-06","decision":"2012-06-27","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.e","B.II.b.1.b","B.II.b.2.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch-release, batch control, primary and secondary packaging, for non-sterile medicinal products; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to batch release arrangements and quality control testing of the FP - Including batch control/testing"}, {"id":"II/0028","type":"II","opinion":"2011-09-22","decision":"2011-10-24","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of SmPC section 4.8 with the adverse drug reactions \"rhabdomyolysis\" and \"leucocytoclastic vasculitis\" under the frequency category \"rare\" as requested by CHMP with assessment of PSUR 8. The PL has been amended accordingly. The MAH also took the opportunity to update the List of Local Representatives."}, {"id":"IA/0029/G","type":"IA","opinion":"2011-08-15","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["A.1","A.4","A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH; Administrative change - Change in the name and/or address of a manufacturer or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS; Administrative change - Change in the name and/or address of a manufacturer responsible for batch release"}, {"id":"II/0027","type":"II","opinion":"2011-06-23","decision":"2011-08-01","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of the existing warning in SmPC section 4.4 regarding information on higher mortality observed in the subset of patients with squamous cell carcinoma of the lung treated with sorafenib in combination with platinum-based chemotherapies with results from a second phase III trial."}, {"id":"R/0024","type":"R","opinion":"2011-04-14","decision":"2011-06-29","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0026/G","type":"II","opinion":"2011-03-17","decision":"2011-05-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","5.2"],"scope":"The respective scope of the variations was to update SmPC section 4.5 regarding new data from an interaction study investigating sorafenib in combination with cisplatin. Furthermore, update of SmPC sections 4.2, 4.4 and 5.2 with respect to sorafenib pharmacokinetics in patients with hepatic impairment. In addition, the MAH took the opportunity to update the List of Local Representatives in the package leaflet."}, {"id":"IA/0025/G","type":"IA","opinion":"2011-01-12","decision":null,"affects":["Annex II"],"codes":["C.I.9.c","C.I.9.d","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change in the safety database; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"II/0022/G","type":"II","opinion":"2010-10-21","decision":"2010-11-26","affects":["SmPC","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8","5.1"],"scope":"The respective scope of the variations was to update SmPC section 4.5 with information on the interaction between sorafenib and cyclophosphamide as well as to update SmPC section 4.8 re-including the term \"radiation pneumonitis\" as clarification of the uncommon adverse reaction \"interstitial lung disease-like events\". These changes follow the recommendation provided with the CHMP assessment of the Periodic Safety Update Report (PSUR) 7."}, {"id":"IB/0021/G","type":"IB","opinion":"2010-09-02","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.1","B.II.f.1.d"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data); Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product"}, {"id":"II/0018/G","type":"II","opinion":"2010-07-22","decision":"2010-08-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.8"],"scope":"The respective scope of the variations was to update SmPC section 4.5 regarding interaction between sorafenib and capecitabine as well as to update SmPC section 4.8 with the ADR \"drug-induced hepatitis\" in accordance with assessment of PSUR 6. The Package Leaflet (PL) has been updated accordingly. Furthermore, an update of SmPC section 4.5 regarding interaction between sorafenib and paclitaxel/carboplatin has been performed. Also SmPC section 4.8 has been updated with ADRs \"angioedema\" and \"radiation recall dermatitis\". The PL has been updated accordingly."}, {"id":"IG/0009/G","type":"IG","opinion":"2010-06-18","decision":null,"affects":["Annex II"],"codes":["C.I.9.h","C.I.9.a","C.I.9.b","C.I.9.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system; Changes to an existing pharmacovigilance system as described in the DDPS - Change in the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change in the contact details of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV"}, {"id":"II/0016","type":"II","opinion":"2009-10-22","decision":"2009-11-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of SPC section 4.8 to change the frequency of the term \"congestive heart failure\" to \"common\" and to include further information on this adverse drug reaction, as well as to add the term \"interstitial lung disease-like events\" with the frequency \"uncommon\" following CHMP assessment of PSUR 6. Furthermore, safety information from a study in non-small lung cancer patients has been added to SPC section 4.4. The package leaflet has been updated accordingly."}, {"id":"II/0015","type":"II","opinion":"2009-09-24","decision":"2009-10-15","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Detailed Description of the Pharmacovigilance System"}, {"id":"II/0012","type":"II","opinion":"2009-06-25","decision":"2009-07-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8","5.2"],"scope":"The MAH applied to update of SPC sections 4.4, 4.5 and 5.2 to include information on co-administration with Neomycin or other antibiotics that might interfere with enterohepatic circulation of sorafenib. Furthermore SPC section 4.8 is updated to include the ADRs 'hyperthyroidism' and 'Steven-Johnson syndrome' as well as to change the ADR 'erythema multiforme minor' to 'erythema multiforme'. The Package Leaflet has been revised accordingly."}, {"id":"T/0013","type":"T","opinion":"2009-03-18","decision":"2009-04-07","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"The MAH applied for the transfer of the Marketing Authorisation of Nexavar from Bayer Healthcare AG to Bayer Schering Pharma AG. Transfer of Marketing Authorisation"}, {"id":"IA/0014","type":"IA","opinion":"2009-03-13","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in name and/or address of a manuf. of the active substance (no Ph. Eur. cert. avail.); Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0011","type":"II","opinion":"2009-01-22","decision":"2009-03-02","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"This type II variation concerns an update of section 5.1 of the SPC to include the results of the Asian hepatocellular carcinoma study 11849 (Study 4), upon request by the CHMP following the assessment of the Follow-Up Measure FU2 021.1. Study 11849 (Study 4) was a Phase III, international, multi-centre, randomised, double blind, placebo-controlled study that evaluated the clinical benefit of sorafenib 400 mg (2 x 200 mg tablets) twice daily (bid) versus placebo, both added to Best Supportive Care, in 226 patients with advanced hepatocellular carcinoma (Child-Pugh A only)."}, {"id":"II/0010","type":"II","opinion":"2008-10-23","decision":"2008-11-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"This variation concerned an update of the SPC to delete information in sections 4.4 and 4.5 on the potential risk of decreased sorafenib exposure when administered concomitantly with substances that increase gastric pH. The MAH has provided data from a 3-way, single-dose crossover study in healthy male volunteers, evaluating the effect of food (moderate-fat meal) and the effect of concomitant omeprazole treatment on the bioavailability of sorafenib (the fed study arm was included to serve as a comparison of pH-related effects beyond those attributable to food)."}, {"id":"II/0008","type":"II","opinion":"2008-03-19","decision":"2008-04-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"The MAH applied for a type II variation to update section 4.4 of the SPC with a statement on gastrointestinal perforation and to add the ADRs 'cholecystitis' and 'cholangitis' in section 4.8 of the SPC. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to make some minor editorial changes to the annexes and to update the list of local representatives in the Package Leaflet."}, {"id":"II/0007","type":"II","opinion":"2007-09-20","decision":"2007-10-29","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"The MAH applied for a type II variation to update sections 4.2 and 5.2 of the SPC, based on the results of Study 11804, with further recommendations for patients with renal impairment. In four Phase I clinical trials, steady state exposure to sorafenib was similar in patients with mild or moderate renal impairment compared to the exposures in patients with normal renal function. In a clinical pharmacology study (single dose of 400 mg sorafenib), no relationship was observed between sorafenib exposure and renal function in subjects with normal renal function, mild, moderate or severe renal impairment. No dose adjustment is required in patients with mild, moderate or severe renal impairment."}, {"id":"II/0006","type":"II","opinion":"2007-09-20","decision":"2007-10-29","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"This variation concerned a modification of a statement in section 5.2 of the SPC regarding potential differences in pharmacokinetics between Asian and Caucasian patients. The MAH has provided data from a new pharmacokinetic study in healthy volunteers, comparing the exposure in Caucasian and Asian (Japanese and Chinese) subjects under controlled conditions. In addition, a new population pharmacokinetic analysis was undertaken, wherein pharmacokinetic data from several single-agent phase I studies were analysed. These new data support the deletion of the statement in section 5.2 of the SPC regarding potential differences in pharmacokinetics between Asian and Caucasian patients."}, {"id":"II/0005","type":"II","opinion":"2007-09-20","decision":"2007-10-29","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"\"Treatment of hepatocellular carcinoma\"."}, {"id":"II/0004","type":"II","opinion":"2007-07-19","decision":"2007-08-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"The Marketing Authorisation Holder applied for a type II variation to add the ADR 'keratoacanthoma/ squamous cell cancer of the skin' in section 4.8 of the SPC. The Package Leaflet has been updated accordingly. Based on individual case reports and rather circumstantial mechanistic reasoning, a causal relationship between development of 'keratoacanthoma/ squamous cell cancer of the skin' and sorafenib therapy is considered sufficiently likely to justify the inclusion of these events in section 4.8 of the SPC, and the proposed incidence figure is accepted."}, {"id":"II/0003","type":"II","opinion":"2006-12-14","decision":"2007-01-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"The Marketing Authorisation Holder applied for a type II variation to update section 4.5 of the SPC with information on potential interaction of sorafenib with docetaxel and to make a consequential change to section 4.4. The Package Leaflet has been amended accordingly. Caution is recommended when sorafenib is co-administered with docetaxel. Docetaxel (75 or 100 mg/m2 administered once every 21 days) when co-administered with sorafenib (200 mg twice daily or 400 mg twice daily administered on Days 2 through 19 of a 21-day cycle with a 3-day break in dosing around administration of docetaxel) resulted in a 36-80% increase in docetaxel AUC and a 16-32% increase in docetaxel Cmax."}, {"id":"II/0002","type":"II","opinion":"2006-12-14","decision":"2007-01-24","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"The MAH applied for a type II variation to update section 4.5 of the SPC with the results of interaction study 11883 of sorafenib and rifampicin with a consequential change to section 4.4. Inducers of metabolic enzymes: Administration of rifampicin for 5 days before administration of a single dose of sorafenib resulted in an average 37% reduction of sorafenib AUC. Other inducers of CYP3A4 activity and/or glucuronidation (e.g. Hypericum perforatum also known as St. John's wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone) may also increase metabolism of sorafenib and thus decrease sorafenib concentrations."}, {"id":"II/0001","type":"II","opinion":"2006-11-16","decision":"2007-01-03","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"The MAH applied for a type II variation to update section 4.8 of the SPC with the ADRs \"congestive heart failure\", \"reversible posterior leucoencephalopathy\", \"gastrointestinal perforation\" and to add a qualifyer to indicate that certain ADRs may have a fatal outcome. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to add Bulgarian and Romanian local representatives to the Package Leaflet and to make some minor linguistic changes to the Annexes."} ] }, "sotorasib__lumykras": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/lumykras-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/lumykras-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000339051","type":"II","opinion":"2026-06-25","decision":null,"affects":["SmPC","Annex II"],"codes":["C.9.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update Annex II and the RMP to request an 18-month extension of the due dates for the Specific Obligation (SOB) SOB2 related to the Phase 3 Study 20190341."}, {"id":"II/0010/G","type":"II","opinion":"2024-09-19","decision":"2024-10-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","5.2"],"scope":"Update of sections 4.2, 4.4, 4.5, 4.8 and 5.2 of the SmPC in order to update safety and efficacy information based on results from study 20190009 (CodeBreaK 200) listed as a specific obligation in the Annex II, and on results from study 20170543 (CodeBreak 100) Phase 2 Part B. Study 20190009 is a Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of sotorasib Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C; while study 20170543 is a Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of sotorasib monotherapy in…"}, {"id":"X/0009","type":"X","opinion":"2024-03-21","decision":"2024-05-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"II/0007","type":"II","opinion":"2024-01-11","decision":"2024-05-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to update recommendations for patients with moderate to severe hepatic impairment following final results from study 20200362 listed as a category 3 PASS study in the EU RMP; this is a Phase I clinical study to evaluate the pharmacokinetics (PK) of a single oral dose of sotorasib administered in subjects with moderate or severe hepatic impairment compared with subjects who have normal hepatic function. The EU RMP version 1.3 has also been agreed. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3."}, {"id":"IB/0016","type":"IB","opinion":"2024-02-12","decision":"2024-05-16","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0011","type":"II","opinion":"2023-09-14","decision":"2023-10-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5"],"scope":"Update of sections 4.2 and 4.5 of the SmPC in order to update information regarding the co-administration of sotorasib with acid reducing agents, based on the results from study 20220024; this is a phase 1, single-center, open-label drug-drug interaction study to evaluate the impact of omeprazole, a proton pump inhibitor, on the pharmacokinetics of sotorasib co-administered with an acidic beverage in healthy volunteers. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"II/0004","type":"II","opinion":"2022-09-15","decision":"2022-11-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC based on the results of Study 2020042, a phase 1 clinical drug interaction study undertaken to assess the effect of concomitant sotorasib administration on the systemic exposure of breast cancer resistance protein (BCRP) transporter substrates. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet."}, {"id":"II/0003","type":"II","opinion":"2022-09-15","decision":"2022-11-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC based on results from the enteral feeding tube in vitro study (RPT-574024), undertaken to assess the feasibility of administration of sotorasib 120 mg film-coated tablets through an enteral feeding tube. The Package Leaflet was updated accordingly."} ] }, "sugemalimab__cejemly": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/cejemly-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/cejemly-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000383517","type":"N","opinion":"2026-10-22","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives. In addition, the MAH took the opportunity to make minor editorial amendments to the Italian translation."}, {"id":"EMA/VR/0000332420","type":"IAIN","opinion":"2026-02-16","decision":null,"affects":["Annex II","PL"],"codes":["Q.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition or replacement of a site responsible for batch release (QP certification) - Not including batch control/testing"}, {"id":"EMA/VR/0000261157","type":"II","opinion":"2025-10-16","decision":"2025-11-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include the treatment of unresectable stage III non-small-cell lung cancer (NSCLC) with no sensitising EGFR mutations, or ALK, ROS1 genomic tumour aberrations in adults whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy for CEJEMLY, based on final results from study CS1001-301; this is a Phase III, multicentre, randomised, double-blind, placebo-controlled study assessing the efficacy and safety of sugemalimab as consolidation therapy versus placebo in participants with locally advanced or unresectable stage III NSCLC who have not progressed after concurrent or sequential chemoradiotherapy."}, {"id":"PSUSA/00011080/202412","type":"PSUSA","opinion":"2025-07-24","decision":"2025-09-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - sugemalimab"}, {"id":"EMA/N/0000261048","type":"N","opinion":"2025-04-03","decision":"2025-09-17","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet to add a list of local representatives. Additionally, the MAH took the opportunity to align the revision date format of the package leaflet with the latest QRD template and to introduce minor editorial amendments to the Slovenian and Czech package leaflet."}, {"id":"EMA/T/0000244822","type":"T","opinion":"2025-02-04","decision":"2025-03-10","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from SFL Pharmaceuticals Deutschland GmbH to CStone Pharmaceuticals Ireland Limited"}, {"id":"IB/0003","type":"IB","opinion":"2025-02-03","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0002","type":"IB","opinion":"2024-12-11","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation Labelling and"} ] }, "sunitinib__sutent": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/sutent-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/sutent-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000255150","type":"N","opinion":"2025-03-10","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Notification acc. Article 61(3) - Update of the package leaflet with revised contact details of local representative and deletion of 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4."} ] }, "tabelecleucel__ebvallo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ebvallo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/ebvallo-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00011028/202512","type":"PSUSA","opinion":"2026-07-23","decision":"2026-09-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tabelecleucel"}, {"id":"EMA/VR/0000306999","type":"IB","opinion":"2025-11-18","decision":"2026-09-21","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0011/G","type":"II","opinion":"2024-12-12","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["B.I.a.1.e","B.II.b.1.c","B.II.b.2.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Replacement or addition of a manufacturing site for the FP - Site where any manufacturing operation(s) take place, except batch release/control, and secondary packaging, for biol/immunol medicinal products or pharmaceutical forms manufactured by complex manufacturing processes."}, {"id":"IB/0015/G","type":"IB","opinion":"2024-12-10","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.5","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Stability of FP - Change to an approved stability protocol"}, {"id":"IA/0010","type":"IA","opinion":"2024-03-04","decision":null,"affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IB/0007","type":"IB","opinion":"2023-12-19","decision":"2024-02-22","affects":["SmPC","Labelling"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IAIN/0002","type":"IAIN","opinion":"2023-03-09","decision":"2024-02-22","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0001","type":"T","opinion":"2023-01-20","decision":"2023-02-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "tafasitamab__minjuvi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/minjuvi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/minjuvi-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000310661","type":"IB","opinion":"2025-12-18","decision":"2025-12-15","affects":["SmPC"],"codes":["B.II.f.1.b.5","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol; Change in the shelf-life or storage conditions of the finished product - Change to an approved stability protocol"}, {"id":"EMA/VR/0000302636","type":"IB","opinion":"2025-10-24","decision":"2025-12-15","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update Annex II.E of the Product Information and the RMP to change the due date for the Specific Obligation MOR208C310 (frontMIND), from ‘December 2025’ to ‘December 2026’."}, {"id":"EMA/VR/0000269625","type":"II","opinion":"2025-10-30","decision":"2025-12-15","affects":["Annex II"],"codes":["B.I.d.1.a.4","B.I.d.1.c","B.I.b.2.a","B.II.b.4.c","B.I.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of a starting material/reagent/intermedia te used in the manufacturing process of the active substance or change in the manufacturer (including where relevant quality control testing sites)"}, {"id":"EMA/VR/0000255975","type":"II","opinion":"2025-11-13","decision":"2025-12-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include in combination with lenalidomide and rituximab treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least one line of systemic therapy for MINJUVI, based on interim results from study INCMOR 0208-301 (inMIND); this is a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tafasitamab plus lenalidomide and rituximab vs lenalidomide and rituximab in patients with relapsed/refractory (R/R) follicular lymphoma grade 1 to 3a or R/R marginal zone lymphoma. As a consequence, sections 4.1, 4.2, 4.8, 5.1, and 5.2 of the SmPC are updated."}, {"id":"EMA/R/0000256675","type":"R","opinion":"2025-07-24","decision":"2025-09-17","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0018/G","type":"IB","opinion":"2024-09-10","decision":null,"affects":["SmPC","PL"],"codes":["B.II.f.1.b.3","B.II.f.1.d","B.II.f.1.b.5","B.II.f.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Stability of FP - Change in storage conditions of the finished product or the diluted/reconstituted product; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Stability of FP - Change to an approved stability protocol"}, {"id":"II/0012/G","type":"II","opinion":"2023-12-14","decision":"2024-07-17","affects":["Annex II"],"codes":["B.I.a.1.e","B.I.b.2.e","A.4","B.I.b.2.a","B.I.a.1.j"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in test procedure for AS or starting material/reagent/intermediate - Other changes to a test procedure (including replacement or addition) for the AS or a starting material/intermediate; Administrative change - Change in the name and/or address of a manufacturer or an ASMF holder or supplier of the AS, starting material, reagent or intermediate used in the manufacture of the AS or manufacturer of a novel excipient."}, {"id":"II/0008","type":"II","opinion":"2023-05-12","decision":"2023-07-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning on Progressive Multifocal Leukoencephalopathy (PML) based on post-marketing data; the Package Leaflet is updated accordingly. The RMP version 2.0 has also been submitted. In addition, the MAH took the opportunity to implement editorial changes in the SmPC and to bring the PI in line with the latest QRD template version 10.3."}, {"id":"IB/0002","type":"IB","opinion":"2022-01-05","decision":"2022-07-08","affects":["SmPC","Annex II","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IAIN/0001","type":"IAIN","opinion":"2021-09-15","decision":"2022-07-08","affects":["SmPC","Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0004","type":"IA","opinion":"2022-03-30","decision":"2022-07-08","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "tagraxofusp__elzonris": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/elzonris-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/elzonris-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"N/0024","type":"N","opinion":"2023-12-06","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0022","type":"N","opinion":"2023-03-10","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0009","type":"II","opinion":"2022-06-23","decision":"2022-10-14","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.4","5.3"],"scope":"Update of section 4.4 and 5.3 of the SmPC to reflect safety information from the final report from study 20255431 (CRL-263114) 'Characterization of fixed choroid plexus samples from primate study MPI-2231-007 by Immunohistochemistry with DT, CD123, IL-3 and IgG' (MEA002) listed as a category 3 study in the RMP. This is a non-interventional, post-authorisation study on blood brain barrier (BBB) models in order to determine a potential toxicity biomarker to further investigate the risk of choroid plexus lesions. The updated RMP version 2.2 has also been submitted."}, {"id":"IB/0011","type":"IB","opinion":"2022-01-04","decision":"2022-10-14","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"IB/0007/G","type":"IB","opinion":"2021-10-15","decision":"2022-10-14","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0015","type":"IAIN","opinion":"2022-07-13","decision":"2022-10-14","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0010","type":"IAIN","opinion":"2021-12-17","decision":"2022-10-14","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"IA/0017","type":"IA","opinion":"2022-09-22","decision":null,"affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"} ] }, "talazoparib__talzenna": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/talzenna-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/talzenna-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"X/0022","type":"X","opinion":"2025-04-25","decision":"2025-06-19","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"EMA/VR/0000248384","type":"II","opinion":"2025-06-05","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the final overall survival results from study C3441021 (TALAPRO-2) listed as a PAES in the Annex II.D, in order to fulfil ANX/01307; study C3441021 (TALAPRO-2)"}, {"id":"IB/0021","type":"IB","opinion":"2024-08-30","decision":"2025-03-28","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0020","type":"IB","opinion":"2024-04-26","decision":"2025-03-28","affects":["SmPC"],"codes":["B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"R/0017","type":"R","opinion":"2024-02-22","decision":"2024-04-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"X/0015/G","type":"X","opinion":"2023-11-09","decision":"2024-01-05","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Change(s) to therapeutic indication(s) - Addition of a new therapeutic indication or modification of an approved one; Annex I_2.(c) Change or addition of a new strength/potency"}, {"id":"N/0011","type":"N","opinion":"2021-09-21","decision":"2022-11-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0010/G","type":"II","opinion":"2021-11-11","decision":"2022-11-09","affects":["SmPC","PL"],"codes":["A.6","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of section 4.4 of the SmPC in order to update the frequency of myelodysplastic syndrome/acute myeloid syndrome (MDS/AML) based on a cumulative safety review; Update of section 5.1 of the SmPC with the revised ATC code. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and make minor corrections in the SmPC and PL."}, {"id":"IB/0012","type":"IB","opinion":"2021-12-06","decision":"2022-11-09","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0009","type":"II","opinion":"2021-04-22","decision":"2021-05-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 based on the results from PK study MDV3800-02 (C3441002), a phase 1 open-label pharmacokinetics and safety study of talazoparib (MDV3800) in patients with advanced solid tumours and normal or varying degrees of hepatic impairment. In addition, the MAH took the opportunity to update the list of local representatives in the package leaflet."}, {"id":"II/0004","type":"II","opinion":"2020-09-03","decision":"2021-05-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the final OS results from Study 673-301 (C3441009, EMBRACA), a phase 3, open-label, randomised, multicentre study of talazoparib vs chemotherapy in patients with germline BRCA mutated HER-2 negative locally advanced or metastatic breast cancer. In addition, the MAH took the opportunity to the update the list of local representatives in the package leaflet."}, {"id":"II/0001","type":"II","opinion":"2020-05-28","decision":"2020-06-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to change posology recommendations in patients with severe renal impairment and update pharmacokinetic information based on the results from PK study MDV3800-01 (C3441001) listed as a category 3 study in the RMP. The RMP version 1.0 is approved. In addition, the MAH took the opportunity to make minor changes through the product information and to bring the PI in line with the latest QRD template version 10.1."}, {"id":"IB/0003/G","type":"IB","opinion":"2020-03-27","decision":"2020-06-26","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "talimogene-laherparepvec__imlygic": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/imlygic-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/imlygic-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000316733","type":"N","opinion":"2025-12-22","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet to delete 'United Kingdom (Northern Ireland)' from the list of local representatives in line with QRD template v10.4. Additionally, the MAH took the opportunity to introduce minor editorial amendments."}, {"id":"EMA/VR/0000296281","type":"IA","opinion":"2025-10-06","decision":null,"affects":["Annex II"],"codes":["A.5.b","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph."}, {"id":"II/0048","type":"II","opinion":"2022-03-24","decision":"2022-10-14","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC in order to add a new warning about the potential risk of hepatic hemorrhage with the transcutaneous intrahepatic route of administration of talimogene laherparepvec. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0047/G","type":"II","opinion":"2021-11-11","decision":"2022-10-14","affects":["Annex II"],"codes":["B.I.a.1.e","B.II.b.1.c","B.I.a.1.k"],"outcome":"accepted","kind":"other","sections":[],"scope":"The Annex II has been updated to include the IDT Biologika GmbH as active substance manufacturing site."}, {"id":"II/0046","type":"II","opinion":"2021-10-14","decision":"2022-10-14","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission to provide preliminary efficacy results from the phase III part of the Study 20110265 to fulfil the obligation listed in the Annex II of the Product Information. The concerned study is a Phase 1b/3, multicenter trial of talimogene laherparepvec in combination with pembrolizumab compared with placebo in combination with pembrolizumab for treatment of unresectable stage IIIB to IVM1c melanoma. The Annex II is updated accordingly."}, {"id":"II/0057","type":"II","opinion":"2022-10-13","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update to sections 4.4 and 4.8 of the SmPC to revise the safety instructions regarding the risk of disseminated herpetic infection adverse drug reactions following an MAH review of aggregate safety data of herpetic and disseminated herpetic infections that were reported in patients who were not immunocompromised and those who were immunocompromised. The Package Leaflet is updated accordingly."}, {"id":"II/0054","type":"II","opinion":"2022-09-15","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["6.6"],"scope":"The SmPC section 6.6. has been updated as follows: Before use, thaw frozen Imlygic vials at room temperature (20°C to 25°C) until Imlygic is liquid. The time to achieve complete vial thaw is expected to be 30 to 70 minutes, depending on the ambient temperature. The PL have been updated accordingly."}, {"id":"R/0039","type":"R","opinion":"2020-09-17","decision":"2020-11-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0035","type":"IB","opinion":"2019-07-22","decision":"2020-07-17","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0029","type":"II","opinion":"2019-03-28","decision":"2019-06-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to update the pharmacokinetic properties information based on the final results from study 20120324, a phase 2, multicenter, single-arm trial to evaluate the biodistribution and shedding of talimogene laherparepvec in subjects with unresected, stage IIIB to IVM1c melanoma. This submission fulfils MEA 006.1. The RMP is updated accordingly (final consolidated version 6.0). In addition, the Marketing authorisation holder (MAH) took the opportunity to update Annex II as per the already assessed EMEA/H/C/002771/ANX/001 procedure."}, {"id":"II/0027","type":"II","opinion":"2018-12-13","decision":"2019-06-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add granulomatous dermatitis as new adverse drug reaction with an uncommon frequency and to update the adverse reaction dyspnoea from dyspnoea exertional to dyspnoea. The package leaflet has been aligned accordingly."}, {"id":"IG/0946","type":"IG","opinion":"2018-06-04","decision":"2019-06-06","affects":["PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010459/201710","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-30","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - talimogene laherparepvec"}, {"id":"II/0020","type":"II","opinion":"2018-05-31","decision":"2018-07-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SmPC in order to add the new ADR ‘hypersensitivity’ with a frequency allocation of ‘unknown’. The Package Leaflet is updated accordingly. Further, the MAH is implementing a minor editorial change in section 3 of the SmPC in order to clarify that the current description of the liquid applies to both strengths, and minor changes in section 4.4 of the SmPC and the Package Leaflet regarding sorbitol and sodium subsequent to the revised Annex to the EC guideline on excipients in the labelling (EMA/CHMP/302620/2017). In addition, the MAH took the opportunity to update the contact details of the local representative in Slovenia in the Package Leaflet."}, {"id":"IG/0853","type":"IG","opinion":"2017-11-10","decision":"2018-07-30","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IB/0021/G","type":"IB","opinion":"2018-05-15","decision":"2018-07-30","affects":["SmPC","PL"],"codes":["B.II.f.1.b.5","B.II.f.1.e","B.II.f.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Stability of FP - Change to an approved stability protocol; Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation"}, {"id":"IB/0001/G","type":"IB","opinion":"2016-07-23","decision":"2017-07-06","affects":["SmPC","PL"],"codes":["A.6","B.II.f.1.z","B.II.f.1.b.5","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code; Stability of FP - Change in the shelf-life or storage conditions of the finished product - Other variation; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0013","type":"IAIN","opinion":"2017-04-26","decision":"2017-07-06","affects":["SmPC","Labelling"],"codes":["B.II.e.6.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that affects the product information"} ] }, "talquetamab__talvey": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/talvey-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/talvey-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000280497","type":"II","opinion":"2025-10-16","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update immunogenicity data based on an updated Integrated Summary of Immunogenicity. In addition, the MAH took the opportunity to update the excipient information and warning regarding polysorbate, introduce editorial changes to the PI and update the list of local representatives in the Package Leaflet."}, {"id":"EMA/VR/0000286343","type":"IB","opinion":"2025-09-26","decision":null,"affects":["SmPC","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/VR/0000264615","type":"II","opinion":"2025-09-04","decision":null,"affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the interim report from study 64407564MMY1001 listed as a Specific Obligation in the Annex II of the Product Information. This is a phase 1/2, first-in-human, open-label, dose escalation study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in subjects with relapsed or refractory multiple myeloma. Safety data were revised based on the 2-year follow-up analysis for the pivotal RP2D population The Annex II and the RMP version 3.2 are updated accordingly."}, {"id":"EMA/VR/0000258454","type":"II","opinion":"2025-09-04","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to add a new warning on Ataxia/Balance disorder based on post-marketing data. The Package Leaflet is updated accordingly. The RMP version 3.1 has also been submitted."}, {"id":"PSUSA/00000099/202408","type":"PSUSA","opinion":"2025-03-27","decision":"2025-06-02","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - talquetamab"}, {"id":"IB/0007/G","type":"IB","opinion":"2024-04-16","decision":"2025-06-02","affects":["SmPC","Labelling","PL"],"codes":["C.I.z","A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"IAIN/0011","type":"IAIN","opinion":"2024-06-24","decision":"2025-06-02","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IB/0004","type":"IB","opinion":"2024-03-12","decision":"2024-06-13","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0002","type":"IB","opinion":"2024-01-04","decision":"2024-06-13","affects":["Annex II"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"IB/0001/G","type":"IB","opinion":"2023-11-23","decision":"2024-06-13","affects":["SmPC"],"codes":["B.I.d.1.a.4","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of AS - Change in the re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "tarlatamab__imdylltra": { "source": [], "procedures": [] }, "tasonermin__beromun": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/beromun-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/beromun-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000342387","type":"IB","opinion":"2026-05-26","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data, fully in line with the stability protocol)"}, {"id":"IB/0057","type":"IB","opinion":"2021-12-09","decision":"2022-11-28","affects":["Annex II"],"codes":["B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IAIN/0048","type":"IAIN","opinion":"2020-03-18","decision":"2021-07-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0040","type":"T","opinion":"2018-07-17","decision":"2018-08-23","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0026","type":"N","opinion":"2013-12-06","decision":"2017-10-03","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0033","type":"IB","opinion":"2017-01-14","decision":"2017-10-03","affects":["SmPC","PL"],"codes":["B.II.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality change - Finished product - Other variation"}, {"id":"IB/0032","type":"IB","opinion":"2016-09-27","decision":"2017-10-03","affects":["SmPC","Labelling","PL"],"codes":["B.II.a.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of the solvent/diluent container from the pack"}, {"id":"II/0024","type":"II","opinion":"2012-11-15","decision":"2013-11-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC to add the adverse reaction peripheral arterial occlusive disease with a frequency uncommon at the request from the CHMP following the assessment of PSUR 10. The package Leaflet is updated accordingly. The MAH also took the opportunity to update the product information in line with the latest QRD template (version 8.1) and to update the list of local representatives in the Package leaflet."}, {"id":"II/0020","type":"II","opinion":"2011-06-23","decision":"2011-07-27","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8"],"scope":"Update of section 4.8 of the Summary of Product Characteristics (SmPC) further to a review of the methodology applied for the estimation of frequency of adverse reactions and extension of the safety dataset. Changes were also proposed to bring this section in line with the EU SmPC guideline. The Package leaflet has been updated accordingly."}, {"id":"IA/0017","type":"IA","opinion":"2009-03-27","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in name and/or address of a manuf. of the active substance (no Ph. Eur. cert. avail.); Change in the name and/or address of a manufacturer of the finished product"}, {"id":"R/0015","type":"R","opinion":"2009-01-22","decision":"2009-03-25","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"R/0010","type":"R","opinion":"2004-02-26","decision":"2004-06-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0008","type":"II","opinion":"2003-09-25","decision":"2004-01-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"N/0007","type":"N","opinion":"2002-12-15","decision":"2002-12-16","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0005","type":"II","opinion":"2001-08-23","decision":"2002-01-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"}, {"id":"N/0003","type":"N","opinion":"1999-05-25","decision":"1999-07-29","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"I/0002","type":"I","opinion":"1999-05-25","decision":"1999-07-29","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in or addition of manufacturer(s) of active substance"}, {"id":"I/0001","type":"I","opinion":"1999-05-25","decision":"1999-07-29","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name of a manufacturer of the medicinal product"} ] }, "tebentafusp__kimmtrak": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kimmtrak-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kimmtrak-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000313831","type":"IA","opinion":"2025-12-08","decision":null,"affects":["SmPC","PL"],"codes":["A.6","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in ATC Code / ATC Vet Code; Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible do not include batch release"}, {"id":"EMA/VR/0000254288","type":"IAIN","opinion":"2025-03-06","decision":null,"affects":["Annex II"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"PSUSA/00010991/202401","type":"PSUSA","opinion":"2024-09-19","decision":"2024-11-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tebentafusp"}, {"id":"N/0003","type":"N","opinion":"2023-10-04","decision":"2024-11-14","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0005","type":"II","opinion":"2024-06-20","decision":"2024-11-14","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to include the updated Overall Survival (OS) data based on results from study IMCgp100-202; this is a phase III randomized, open-label, multi-center study of the safety and efficacy of IMCgp100 compared with investigator’s choice in HLA-A*0201 positive patients with previously untreated advanced uveal melanoma."} ] }, "teclistamab__tecvayli": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tecvayli-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tecvayli-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000322279","type":"II","opinion":"2026-06-25","decision":"2026-08-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.7","4.8","5.1","5.2","6.6"],"scope":"Extension of indication to include in combination with daratumumab treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy for TECVAYLI, based on interim analysis data from the pivotal study MajesTEC-3 (64007957MMY3001). This is an on-going multicentre, randomised, open-label, Phase 3 study to determine whether adding teclistamab to daratumumab (Tec-Dara) is more efficacious than adding pomalidomide/dexamethasone (DPd) or bortezomib/dexamethasone (DVd) to daratumumab in participants with multiple myeloma who previously received 1 to 3 prior line(s) of therapy."}, {"id":"EMA/VR/0000362254","type":"IB","opinion":"2026-08-07","decision":null,"affects":["SmPC","PL"],"codes":["Q.II.f.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Q.II.f.1.b) Extension of the shelf life of the finished product - After first opening (supported by real time data) – Accepted"}, {"id":"PSUSA/00011010/202508","type":"PSUSA","opinion":"2026-03-26","decision":"2026-05-21","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - teclistamab"}, {"id":"EMA/VR/0000254941","type":"II","opinion":"2025-06-12","decision":"2025-08-12","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.4 of the SmPC in order to include the term ‘fatal’ under the warning for Neurologic Toxicities, including ICANS. In addition, the MAH took the opportunity to introduce minor changes to section 4.2 of the SmPC in order to update the intervals regarding the restarting of teclistamab after a dose delay. Furthermore, the MAH took the opportunity to update the PI with the excipient information on polysorbate following the latest EU Excipients Guideline as well as to update the list of local representatives in the Package Leaflet."}, {"id":"II/0012","type":"II","opinion":"2024-05-30","decision":"2025-08-11","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.2, 4.8, 5.1 of the SmPC in order to amend the recommendations for dose delays, as well as, to update safety and efficacy information based on final results from study 64007957MMY1001 listed as a specific obligation in the Annex II (SOB/005); this is a phase 1/2, first in human, open label, dose escalation study of teclistamab in subjects with relapsed or refractory multiple myeloma. The Package Leaflet is updated accordingly. The RMP version 4.2 has also been submitted. In addition, the MAH took the opportunity to update Annex II and Annex IV of the PI."}, {"id":"II/0009","type":"II","opinion":"2024-07-11","decision":"2025-08-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to update the warning on Progressive Multifocal Leukoencephalopathy (PML) based on a cumulative safety review and to include PML as new ADR with uncommon frequency. The Package Leaflet is updated accordingly. The RMP version 4.1 has also been submitted. In addition, the MAH took the opportunity to introduce minor updates to the PI and to update the list of local representatives in the Package Leaflet."}, {"id":"IB/0013/G","type":"IB","opinion":"2024-05-28","decision":"2025-08-11","affects":["SmPC","Annex II","PL"],"codes":["B.II.f.1.b.5","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00011010/202302","type":"PSUSA","opinion":"2023-10-12","decision":"2023-12-07","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - teclistamab PSUSA/11010/202302."}, {"id":"II/0006","type":"II","opinion":"2023-07-20","decision":"2023-08-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to update the posology recommendations to include the possibility of bi-weekly dosing, based on interim results from study 64007957MMY1001 (MajesTEC-1); this is a phase 1/2, single-arm, open-label, multicenter study of teclistamab administered as monotherapy to adult subjects with relapsed or refractory multiple myeloma. The Package Leaflet is updated accordingly. The RMP version 2.3 as also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and update the list of local representatives in the Package Leaflet."}, {"id":"II/0003","type":"II","opinion":"2023-06-22","decision":"2023-08-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.6","5.2"],"scope":"Update of sections 4.2, 4.6 and 5.2 of the SmPC in order to revise the dosing schedule, amend recommendations on contraception and breast-feeding and to update pharmacokinetic information, based on the latest data available; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and update the list of local representatives in the Package Leaflet."} ] }, "temsirolimus__torisel": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/torisel-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/N/0000246449","type":"N","opinion":"2025-02-25","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representative and deletion of 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4."} ] }, "tepotinib__tepmetko": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tepmetko-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tepmetko-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000337926","type":"IB","opinion":"2026-04-17","decision":"2026-09-14","affects":["SmPC","Labelling","PL"],"codes":["Q.II.a.3.b.4","Q.II.b.3.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Other excipients - Replacement of excipient(s) with comparable excipient(s) with the same functional characteristics; Change in the manufacturing process of the finished product, including an intermediate used in the manufacture of the finished product - Minor change in the manufacturing process"}, {"id":"EMA/R/0000339701","type":"R","opinion":"2026-07-23","decision":"2026-09-14","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of marketing authorisation"}, {"id":"II/0011","type":"II","opinion":"2024-04-18","decision":"2024-06-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to add alternative methods of administration dispersed in water, as oral drinking suspension or via feeding tubes based on the available physicochemical and clinical pharmacology data. The Section 3 of the Package Leaflet is updated accordingly."}, {"id":"II/0009","type":"II","opinion":"2023-08-31","decision":"2024-06-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update safety and efficacy information based on updated results from study VISION (MS200095-0022); this is a Phase II, multicenter, open-label, single-arm study to evaluate the efficacy and safety/tolerability of the recommended dose of tepotinib in participants with advanced NSCLC of all histology types who tested positive for METex14 skipping alterations by next-generation sequencing in tissue (RNA-based) or plasma (circulating tumor DNA based). The RMP version 2.0 is agreed. In addition, the MAH took the opportunity to implement editorial changes to the SmPC."}, {"id":"II/0005","type":"II","opinion":"2023-06-15","decision":"2024-06-06","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4, 4.5 and 5.2 of the SmPC in order to remove the warnings on interactions with ‘CYP and P-gp inducers’ and ‘dual strong CYP3A and P-gp inhibitors, and P-gp inhibitors’ and to update pharmacokinetic information based on final results from the drug-drug interaction (DDI) studies MS200095-0051 and MS200095-0053."} ] }, "thalidomide__thalidomide-bms-previously-thalidomide-celgene-": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/thalidomide-bms-previously-thalidomide-celgene-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"N/0080","type":"N","opinion":"2025-01-21","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0076","type":"II","opinion":"2023-06-08","decision":"2023-07-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimisation measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)- approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted."}, {"id":"T/0073","type":"T","opinion":"2021-11-26","decision":"2021-12-13","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IAIN/0072/G","type":"IAIN","opinion":"2021-11-04","decision":"2021-12-09","affects":["SmPC","Labelling","PL"],"codes":["B.II.a.1.a","A.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change or addition of imprints, bossing or other markings including replacement, or addition of inks used for product marking - Changes in imprints, bossing or other markings; Administrative change - Change in the (invented) name of the medicinal product for CAPs"}, {"id":"IAIN/0071/G","type":"IAIN","opinion":"2021-10-14","decision":"2021-12-09","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"PSUSA/00002919/202010","type":"PSUSA","opinion":"2021-05-20","decision":"2021-07-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - thalidomide"}, {"id":"II/0066","type":"II","opinion":"2021-03-25","decision":"2021-07-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 to include PML. This change is being introduced following the approval of version 11 of the Company Core Data Sheet (CCDS) for thalidomide. The PIL is updated accordingly."}, {"id":"II/0061/G","type":"II","opinion":"2020-04-30","decision":"2020-06-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.z","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","6.6"],"scope":"Group of variations including one type II to update sections 4.2, 4.4 and 4.8 of the SmPC and section 4 of the PL with anaphylactic reactions with a not known frequency following a safety review and a Type IB to update section 6.6 of the SmPC in order to include recommendations to minimise the risk of unintended occupational exposures in healthcare professionals. The MAH has also proposed minor updates to section 4.4 of the SmPC and Annex IID regarding the educational materials, prescribing and dispensing restrictions in order to provide more clarity."}, {"id":"PSUSA/00002919/201810","type":"PSUSA","opinion":"2019-05-29","decision":"2019-07-31","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - thalidomide"}, {"id":"II/0056","type":"II","opinion":"2019-02-14","decision":"2019-07-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6"],"scope":"Update of the RMP version 19.2 in line with the updated Guideline on Good Pharmacovigilance Practices (GVP) Module V to propose the reclassification and/or renaming of known safety concerns associated with the use of thalidomide and to provide more detail in relation to the pregnancy prevention. Consequently, Annex IID, SmPC sections 4.4 and 4.6 and the PL have been updated accordingly. Minor editorial changes have been introduced in the PI."}, {"id":"IAIN/0058","type":"IAIN","opinion":"2018-10-11","decision":"2019-07-31","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IA/0060","type":"IA","opinion":"2019-05-07","decision":"2019-07-31","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"T/0057","type":"T","opinion":"2018-07-30","decision":"2018-08-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"PSUSA/00002919/201710","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-30","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - thalidomide"}, {"id":"R/0054","type":"R","opinion":"2017-12-14","decision":"2018-02-08","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0049","type":"IB","opinion":"2017-02-01","decision":"2018-02-08","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation and PL"}, {"id":"PSUSA/00002919/201510","type":"PSUSA","opinion":"2016-05-26","decision":"2016-07-15","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - thalidomide"}, {"id":"II/0043","type":"II","opinion":"2015-10-22","decision":"2015-11-19","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Update of sections 4.2 and 4.8 of the SmPC in order to add new dosing information for elderly patients (>75 years) with untreated multiple myeloma receiving thalidomide in combination with melphalan and prednisone (MPT). In addition the MAH is updating the posology with the recommended starting doses for melphalan and prednisone for completeness. The Package Leaflet is being updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet. A revised RMP version 17 was agreed during the procedure."}, {"id":"IB/0041","type":"IB","opinion":"2014-06-20","decision":"2015-05-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To clarify the wording in the Package Leaflet for myocardial infarction and thromboembolic events and other minor editorial revisions and to update the description of the immediate packaging in Annex A in line with the Summary of Product Characteristics. In addition to update the Product Information to QRD v9.0."}, {"id":"II/0033","type":"II","opinion":"2013-02-21","decision":"2013-04-09","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8"],"scope":"Update of sections 4.2, 4.4 and 4.8 of the Summary of Product Characteristics following the assessment of EU PSUR 06 covering the reporting period from 09 October 2010 to 10 October 2011 with safety information regarding grade 3-4 neutropenia, grade 3-4 thrombocytopenia, haematological disorders and hepatic disorders. The Package leaflet is updated accordingly. The MAH also took the opportunity to include the date of latest renewal."}, {"id":"II/0032","type":"II","opinion":"2013-02-21","decision":"2013-04-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to add a warning and information on acute myeloid leukaemia and myelodysplatic syndromes as second primary maligancies in patients treated with thalidomide, as reported in study CC-5013-MM- 020 and further to a safety review conducted by the MAH. The Package Leaflet is updated accordingly. The Annex II of the Product Information was also updated to include the requirement to circulate the DHPC in countries where Thalidomide Celgene is already launched, informing healthcare professionals of the risk of second primary malignancies with thalidomide. Finally, the PI is being brought in line with the latest QRD template version 8.3."}, {"id":"II/0027/G","type":"II","opinion":"2012-12-13","decision":"2013-04-09","affects":["SmPC","Labelling","PL"],"codes":["B.II.a.3.b.2","B.II.b.3.b","B.II.d.1.z","B.II.d.2.a","B.II.d.2.d","B.II.b.1.e","B.II.b.2.a","B.II.e.1.a.1","B.II.f.1.b.1","B.III.2.b","B.II.b.1.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Group of variations relating to the change in the formulation of Thalidomide Celgene, including: - changes to the qualitative and quantitative composition of excipients; replacement of currently approved six excipients (microcrystalline cellulose, povidone, stearic acid, colloidal anhydrous silica, crospovidone and anhydrous lactose) with two excipients (pregelatinised starch and magnesium sterate), - change in the manufacturing process - minor changes to the finished product specification to update the acceptance criteria and test procedure for appearance - minor changes to the test procedure for assay and identity, related impurities, dissolution and content uniformity - change in the…"}, {"id":"R/0030","type":"R","opinion":"2012-10-18","decision":"2012-12-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0028","type":"II","opinion":"2012-07-19","decision":"2012-08-23","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to add a new warning and update the safety information regarding allergic reactions (angioedema/urticaria) further to a safety review conducted by the MAH. The Package Leaflet is updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2011-10-20","decision":"2011-11-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) and the package leaflet with information on the risks of amenorrhoea, severe infections, atrioventricular block, atrial fibrillation, pancreatitis and convulsions further to the request of the CHMP during the assessment of the 5th Periodic Safety Update Report (PSUR). The MAH also took the opportunity to make a minor editorial change in the labelling."}, {"id":"IA/0019","type":"IA","opinion":"2011-06-07","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"IA/0018","type":"IA","opinion":"2011-05-04","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"II/0017","type":"II","opinion":"2011-02-17","decision":"2011-04-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SmPC) with information on the risks of myocardial infarction and arterial thromboembolic events and update of section 4.8 of the SmPC with regards to the risk of worsening of Parkinson's disease symptoms further to the request of the CHMP in the assessment of the 4th PSUR. Annex II, Annex 127a and the Package Leaflet have been updated accordingly."}, {"id":"II/0015","type":"II","opinion":"2010-11-18","decision":"2010-12-20","affects":["SmPC","Annex II"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","5.2"],"scope":"Update of sections 4.4, 4.5 and 5.2 of the Summary of Product Characteristics with all relevant pharmacokinetics data on thalidomide collected from FU2 003.1 and FU2 003.2, as requested by the CHMP. The Marketing Authorisation Holder also took the opportunity to update Annex II with the deletion of the version number of the DDPS and with the latest agreed version number of the RMP (version 10.0)."}, {"id":"II/0014","type":"II","opinion":"2010-10-21","decision":"2010-11-26","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of sections 4.8 of the Summary of Product Characteristics (SmPC) to add the adverse drug reactions pancytopenia, hearing loss, renal dysfunction and hypersensitivity, reported in the post-marketing experience, as requested by the CHMP in the assessment of the 3rd Periodic Safety Update Report. The Package Leaflet has been updated accordingly. In addition, the MAH took the opportunity to align the product information with the latest QRD template (version 7.3.1) and to include the version number of the latest agreed risk management plan in Annex II (version 9.0)."}, {"id":"IA/0016","type":"IA","opinion":"2010-10-14","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to batch release arrangements and quality control testing of the FP - Not including batch control/testing"}, {"id":"IA/0013/G","type":"IA","opinion":"2010-07-08","decision":null,"affects":["Annex II"],"codes":["C.I.9.a","C.I.9.c","C.I.9.e","C.I.9.h"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes to an existing pharmacovigilance system as described in the DDPS - Change in the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Change of the back-up procedure of the QPPV; Changes to an existing pharmacovigilance system as described in the DDPS - Changes in the major contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations and described in the DD; Changes to an existing pharmacovigilance system as described in the DDPS - Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system"}, {"id":"II/0011","type":"II","opinion":"2010-02-18","decision":"2010-03-23","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the Summary of Product Characteristics (SPC) with information regarding the risk of tumour lysis syndrome (TLS) and to update section 4.8 of the SPC to add the adverse drug reactions febrile neutropenia and gastrointestinal perforations reported in the post-marketing experience, as requested by the CHMP further to the assessment of the 2nd Periodic Safety Update Report. The Package Leaflet has been updated accordingly."}, {"id":"II/0010","type":"II","opinion":"2010-02-18","decision":"2010-03-23","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SPC with results of human mass balance study clarifying the route and fate of elimination of thalidomide, as requested by the CHMP following the assessment of FUM 002."}, {"id":"IA/0012","type":"IA","opinion":"2009-12-16","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"II/0007","type":"II","opinion":"2009-09-24","decision":"2009-10-19","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS) to version 6.0, in light of a reorganisation within Celgene's Drug Safety Department concerning the risk management activities. Consequently, Annex II has been updated with the new version number of the agreed DDPS."}, {"id":"II/0008","type":"II","opinion":"2009-07-23","decision":"2009-08-27","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.3","4.4","4.6"],"scope":"The Marketing Authorisation Holder proposed a minor update section 4.4 of the Summary of Product Characteristics (SPC) to align the reference to the conditions of the Pregnancy Prevention Programme in line with the wording from sections 4.3 and 4.6 of the SPC. Minor editorial changes and changes to bring in line with QRD template were also proposed to the Package Leaflet."}, {"id":"II/0006","type":"II","opinion":"2009-01-22","decision":"2009-02-24","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SPC with regard to the recommended dose modifications due to peripheral neuropathy, further to the request of the CHMP following the review of available data to justify the extent of reduction of dose in case of thalidomide-related neuropathy."}, {"id":"II/0003","type":"II","opinion":"2008-10-23","decision":"2009-01-30","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Detailed Description of the Pharmacovigilance System (DDPS). Consequently, Annex II of the product information has been updated to include the latest version number (version 5.1) of the DDPS agreed by the CHMP."}, {"id":"IB/0005","type":"IB","opinion":"2008-10-22","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name of the medicinal product"}, {"id":"T/0004","type":"T","opinion":"2008-10-03","decision":"2008-10-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation from Pharmion Ltd. to Celgene. Transfer of Marketing Authorisation"}, {"id":"N/0001","type":"N","opinion":"2008-07-04","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "thalidomide__thalidomide-lipomed": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/thalidomide-lipomed-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/thalidomide-lipomed-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IB/0003","type":"IB","opinion":"2024-04-22","decision":"2024-05-10","affects":["SmPC","Annex II","Labelling"],"codes":["C.I.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the SPC, Labelling or PL of a generic/hybrid/biosimilar products following assessment of the same change for the reference product - Implementation of change(s) for which NO new additional data is required to be submitted by the MAH"} ] }, "tisagenlecleucel__kymriah": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kymriah-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kymriah-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000358424","type":"IB","opinion":"2026-09-01","decision":null,"affects":["Annex II"],"codes":["C.9.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"To update the RMP with the following changes: - removal of Pharmacy/Cell Lab/Infusion Center Training Material in line with PRAC recommendation (EMEA/H/C/PSUSA/00010702/202408); - addition of post-marketing experience from PASS CCTL019B2401 (PSUSA/00010702/202508); - updated milestones as per final protocol of PASS CCTL019B2402 (EMA/PAM/0000258545); - update to clinical trial exposure with final data from CCTL019B2202 (EMEA/H/C/004090/II/0071) and CCTL019C2201 (EMEA/H/C/004090/II/0075)."}, {"id":"EMA/VR/0000309349","type":"IA","opinion":"2025-11-06","decision":"2026-05-06","affects":["Annex II","PL"],"codes":["B.II.c.1.c","A.7","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of an excipient - Deletion of a non-significant specification parameter (e.g. deletion of an obsolete parameter); Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*."}, {"id":"EMA/VR/0000300811","type":"IAIN","opinion":"2025-09-24","decision":"2026-05-06","affects":["SmPC"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"To update section 4.4 of the SmPC to implement the signal recommendations on 'Ciltacabtagene autoleucel; idecabtagene vicleucel; tisagenlecleucel – Progressive multifocal leukoencephalopathy (EPITT No 20153)' adopted at the 10 July 2025 PRAC."}, {"id":"EMA/VR/0000248534","type":"II","opinion":"2025-04-25","decision":"2026-05-06","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the interim report from study CCTL019H2301 / BELINDA, including final overall survival results, listed as an obligation in the Annex II of the Product Information. This is an open label, phase III PAES of Kymriah versus standard of care in adult patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma. The Annex II is updated accordingly."}, {"id":"PSUSA/00010702/202408","type":"PSUSA","opinion":"2025-03-27","decision":"2025-05-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tisagenlecleucel"}, {"id":"II/0092","type":"II","opinion":"2025-03-27","decision":"2025-05-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC in order to update the 'monitoring after infusion' recommendations, based on existing clinical trial data as well as literature references reporting real word experience. The Package Leaflet is updated accordingly. The RMP version 8.1 has also been submitted. In addition, the MAH took the opportunity to introduce a minor change to the HCP educational programme in the Annex II in order to enhance readability."}, {"id":"II/0086/G","type":"II","opinion":"2025-02-27","decision":"2025-05-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"A grouped application consisting of: C.I.4: Update of section 4.4 of the SmPC in order to amend existing warnings on cytokine release syndrome based on literature. C.I.4: Update of section 4.4 of the SmPC in order to amend existing warnings on neurological adverse reaction based on literature. The Package Leaflet is updated accordingly. C.I.4: Update of section 4.4 of the SmPC in order to amend existing warnings on hypersensitivity reactions based on post marketing data and literature. The Package Leaflet is updated accordingly. In addition, a new warning of CD19-negative disease ALL patients has been included in section 4.4 of the SmPC."}, {"id":"II/0075","type":"II","opinion":"2024-02-22","decision":"2025-02-28","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1","5.2"],"scope":"Update of sections 5.1 and 5.2 of the SmPC to update efficacy and pharmacokinetic information based on final results from study Cl.CTL019C2201 PAES in the Annex II (ANX008); this is a Phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The RMP version 6 has also been submitted. In addition, Annex II.D of the product information is updated to reflect that the obligation to conduct the mention study is fulfilled."}, {"id":"II/0071","type":"II","opinion":"2024-02-22","decision":"2025-02-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1","5.2"],"scope":"Update of sections 5.1 and 5.2 of the SmPC to update efficacy and pharmacokinetic information based on final results from study CCTL019B2202 (a phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in paediatric patients with relapsed and refractory B-cell acute lymphoblastic leukemia). Submission of cellular kinetic report for the B-cell acute lymphoblastic leukaemia (ALL) indication based on data from pivotal study CCTL019B2202 and the supportive study CCTL019B2205J involving paediatric ALL patients (partially fulfil REC). In addition, the MAH took this opportunity to introduce editorial changes."}, {"id":"IAIN/0091/G","type":"IAIN","opinion":"2024-11-18","decision":"2025-02-28","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IAIN/0084","type":"IAIN","opinion":"2024-08-01","decision":"2025-02-28","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0068","type":"R","opinion":"2023-02-23","decision":"2023-04-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0062","type":"II","opinion":"2022-09-15","decision":"2023-04-26","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final report from study CCTL019B2401 listed as a category 1 study in the Annex II of the Product Information in order to fulfil ANX/007.3. This is a sub-analysis (PAES) to assess efficacy in patients with relapsed or refractory diffuse large B-cell lymphoma based on data from the registry study to assess the long-term safety of patients with B lymphocyte malignancies treated with tisagenlecleucel. The Annex II is updated accordingly."}, {"id":"II/0060","type":"II","opinion":"2022-09-15","decision":"2023-04-26","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1"],"scope":"Update of section 4.2 of the SmPC in order to update the paediatric statement for the B-cell ALL indication and section 4.4 to update the warning on ‘prior treatment with anti-CD19 therapy’ as well as sections 4.4 and 4.8 in order to update safety data to reflect the pool of the 3 studies B2202, B2205J and B2001X. The proposed changes are in line with the request of the CHMP following the assessment of P46/012. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to correct the Complete Response Rate (CRR) 95% Confidence Interval (CI) on Enrolled set for E2202 study presented in Table 8 in section 5.1 of the SmPC. The RMP version 5.1 has also been submitted."}, {"id":"II/0059","type":"II","opinion":"2022-10-13","decision":"2023-04-26","affects":["SmPC","Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC based on a subgroup analysis from CCTL019B2401 (B2401) disease registry listed as a PAES (ANX006) in the Annex II; this is a non-interventional study to evaluate the efficacy and safety of Kymriah in ALL patients below the age of 3 years. In addition, the MAH took the opportunity to update Annex II.D of the SmPC to reflect the fulfilment of the PAES."}, {"id":"II/0056","type":"II","opinion":"2022-09-15","decision":"2023-04-26","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.1"],"scope":"Update of sections 4.2 and 5.1 of the SmPC in order to update efficacy and safety information in paediatric population based on study CCTL019C2202, a phase II, single arm, multicenter open label trial to determine the safety and efficacy of tisagenlecleucel in pediatric patients with relapsed or refractory mature B-cell non-Hodgkin lymphoma (NHL) (BIANCA). The Package Leaflet is updated accordingly."}, {"id":"II/0053","type":"II","opinion":"2022-10-13","decision":"2023-04-26","affects":["Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the results from study CCTL019H2301 (BELINDA) listed as an obligation in the Annex II of the Product Information. This is a randomised open-label parallel-group multicenter Phase III trial to evaluate the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory B-cell aggressive NHL after failure of rituximab and anthracycline containing first-line immune-chemotherapy. The Annex II is updated accordingly."}, {"id":"IB/0064/G","type":"IB","opinion":"2022-10-28","decision":"2023-04-26","affects":["Annex II"],"codes":["B.II.d.2.d","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition); Administrative change - Deletion of manufacturing sites"}, {"id":"II/0044","type":"II","opinion":"2022-03-24","decision":"2022-04-29","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic treatment for Kymriah. As a consequence, Sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC and corresponding sections in the Package Leaflet are updated accordingly. The RMP has been updated to version 4.2 to align with the indication extension. The updates to Module 3 include mainly the incoming FL material characterization, final product characterization and FL batch analyses data."}, {"id":"IB/0048/G","type":"IB","opinion":"2022-02-07","decision":"2022-04-29","affects":["SmPC"],"codes":["B.II.e.6.b","B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that does not affect the product information; Change in the manufacturing process of the finished or intermediate product - Other variation"}, {"id":"N/0041","type":"N","opinion":"2021-09-28","decision":"2022-01-24","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0047","type":"II","opinion":"2021-12-16","decision":"2022-01-24","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC, Annex IID and PIL (information intended for healthcare professionals) in order to add statements for the use of Kymriah exceptionally during shortage of tocilizumab following the \"CAT recommendation for the use of CAR-T cell-based therapies in EU during shortages of tocilizumab\"."}, {"id":"II/0030","type":"II","opinion":"2021-02-25","decision":"2022-01-24","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to include the complete data set (updated overall survival analysis) of study CCTL019B2205J, a Phase II, single arm, multicenter study to determine the efficacy and safety of Kymriah in paediatric subjects with relapsed or refractory B-cell ALL. The clinical results have already been assessed in procedure EMA/H/C/004090/P46/011. In addition, the final ATC code for tisagenlecleucel (L01XX71) has been added as an editorial change."}, {"id":"IB/0039","type":"IB","opinion":"2021-06-18","decision":"2022-01-24","affects":["SmPC","Annex II"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0034/G","type":"IB","opinion":"2021-03-23","decision":"2022-01-24","affects":["SmPC"],"codes":["B.II.e.6.b","B.II.b.3.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in any part of the (primary) packaging material not in contact with the finished product formulation - Change that does not affect the product information; Change in the manufacturing process of the finished or intermediate product - Other variation"}, {"id":"II/0013/G","type":"II","opinion":"2020-02-27","decision":"2021-03-04","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.8","5.1","5.2","6.5"],"scope":"Submission of a group of 3 type II variations (C.I.4) to include: - Long-term efficacy and safety of Kymriah in relapsed/refractory DLBCL based on the 24 months follow-up results from study CCTL019C2201 (update of sections 4.4, 4.8, 5.1 and 5.2 of the SmPC) - Interim results from study CCTL019B2202 (update of sections 4.4, 4.8, 5.1 and 5.2 of the SmPC) - Interim results from study CCTL019B2205J (update section 5.2 of the SmPC) The Marketing authorisation holder (MAH) took the opportunity to clarify the wording of the indication to include patients over 25 years of age and to introduce some minor editorial corrections throughout the SmPC and the Package Leaflet."}, {"id":"IB/0024/G","type":"IB","opinion":"2020-07-17","decision":"2021-03-04","affects":["Annex II","PL"],"codes":["A.5.b","B.II.b.2.c.1","B.II.g.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release); Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"} ] }, "tislelizumab__tevimbra": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tevimbra-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tevimbra-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00000136/202512","type":"PSUSA","opinion":"2026-07-23","decision":"2026-09-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"EURD: PSUSA/00000136/202512 Active"}, {"id":"EMA/VR/0000290059","type":"II","opinion":"2026-05-21","decision":"2026-09-18","affects":["Annex II"],"codes":["B.I.b.2.a","B.II.d.2.a","B.II.d.2.d","B.I.a.1.g","B.II.b.1.c","B.I.a.1.k","B.I.a.1.j","B.II.b.2.b","A.4","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for active substance or starting material/reagent/intermediate used in the manufacturing process of the active substance - Minor changes to an approved test procedure; Change in test procedure for the finished product - Minor changes to an approved test procedure; Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition); Change in the manufacturer of a starting material/reagent/intermediate used in the manufacturing process of the active substance or change in the manufacturer (including where relevant quality control testing sites) of the active substance, where no Ph."}, {"id":"EMA/VR/0000269879","type":"II","opinion":"2025-09-18","decision":"2025-10-24","affects":["SmPC","PL"],"codes":["B.I.a.4.z","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.1","5.2","6.6"],"scope":"A grouped application consisting of: Update of sections 4.2, 5.1, 5.2, and 6.6 of the SmPC in order to introduce an alternative dosing regimen of 400 mg every 6 weeks (Q6W) based on POP-PK and exposure-response analyses, and observed clinical data, and update safety information based on data collected in studies BGB-A317-315 and BGB-A317-212 (400 mg Q6W), and study BGB-A317-001; the Package Leaflet is updated accordingly. The RMP version 4.1 has also been submitted. Minor change to the impurity evaluation analytical procedure for the impurity in-process test to reevaluate impurities for higher clinical doses of 400mg Q6W."}, {"id":"PSUSA/00000136/202412","type":"PSUSA","opinion":"2025-07-24","decision":"2025-09-17","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tislelizumab"}, {"id":"EMA/VR/0000285978","type":"IAIN","opinion":"2025-07-14","decision":"2025-09-17","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"EMA/VR/0000269138","type":"IB","opinion":"2025-06-02","decision":"2025-09-17","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"II/0018","type":"II","opinion":"2025-07-24","decision":"2025-08-21","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","5.1","6.6"],"scope":"Extension of indication for Tevimbra in combination with platinum-containing chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment, for the treatment of adult patients with resectable NSCLC based on interim results from study BGB-A317-315. Study BGB-A317-315 is a phase 3 randomized, placebo-controlled, double-blind study to compare the efficacy and safety of neoadjuvant treatment with tislelizumab plus platinum-based doublet chemotherapy followed by adjuvant tislelizumab versus neoadjuvant treatment with placebo plus platinum-based doublet chemotherapy followed by adjuvant placebo in patients with resectable Stage II or IIIA NSCLC."}, {"id":"II/0017","type":"II","opinion":"2025-05-22","decision":"2025-07-09","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include, in combination with gemcitabine and cisplatin, the first-line treatment of adult patients with recurrent, not amenable to curative surgery or radiotherapy or metastatic nasopharyngeal carcinoma (NPC) for TEVIMBRA based on final results from study BGB-A317-309 (study 309). Study 309 was a Phase 3 randomised, double-blind, placebo-controlled, Asia-only study that compared the efficacy and safety of tislelizumab combined with gemcitabine plus cisplatin (GC) versus placebo combined with GC as 1L treatment for recurrent or metastatic NPC. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000271889","type":"IAIN","opinion":"2025-05-13","decision":"2025-07-09","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"II/0016","type":"II","opinion":"2025-03-27","decision":"2025-05-02","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of indication to include first-line treatment of adult patients with extensive-stage Small Cell Lung Cancer (SCLC) for Tevimbra in combination with etoposide and platinum chemotherapy based on final results from study BGB-A317-312; a phase 3, randomized, double-blind, placebo-controlled study of platinum plus etoposide with or without tislelizumab in patients with untreated extensive-stage small cell lung cancer. As a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. The MAH also took the opportunity to make further changes to the SmPC, Annex II and Package Leaflet (editorial and in line with the SmPC guideline)."}, {"id":"PSUSA/00000136/202406","type":"PSUSA","opinion":"2025-01-30","decision":"2025-03-28","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tislelizumab"}, {"id":"II/0009","type":"II","opinion":"2024-06-20","decision":"2024-11-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on the overall survival (OS) final analyses for study BGB-A317-302; this is a randomized, controlled, open-label, global phase 3 study comparing the efficacy of the anti-PD-1 antibody tislelizumab (BGB-A317) versus chemotherapy as second line treatment in patients with advanced unresectable/metastatic oesophageal squamous cell carcinoma."}, {"id":"II/0006","type":"II","opinion":"2024-10-17","decision":"2024-11-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include in combination with platinum and fluoropyrimidine-based chemotherapy the first-line treatment of adult patients with human epidermal growth factor receptor-2 (HER-2)-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma whose tumours express PD L1 with a tumour area positivity (TAP) score ≥ 5% for TEVIMBRA, based on results from the phase 3 study BGB-A317-305 (study 305); this is a global, randomized, double-blind, placebo-controlled study at the approved registrational dosing regimen for Tevimbra (200 mg administered IV Q3W), in combination with platinum and fluoropyrimidine-based chemotherapy, in…"}, {"id":"II/0003","type":"II","opinion":"2024-10-17","decision":"2024-11-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1"],"scope":"Extension of indication to include in combination with platinum-based chemotherapy the first-line treatment of adult patients with unresectable, locally advanced or metastatic oesophageal squamous cell carcinoma (OSCC) whose tumours express PD-L1 with a tumour area positivity (TAP) score ≥ 5%for TEVIMBRA, based on results from study BGB-A317-306; this is a multi-regional, randomized, placebo-controlled, double-blind phase 3 study evaluating the efficacy and safety of tislelizumab in combination with chemotherapy compared to placebo in combination with chemotherapy as first-line treatment in patients with unresectable or locally advanced recurrent or metastatic OSCC."}, {"id":"IB/0013/G","type":"IB","opinion":"2024-10-09","decision":"2024-11-25","affects":["Annex II"],"codes":["B.I.b.2.z","B.II.g.5.c","B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for AS or starting material/reagent/intermediate - Other variation; Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"II/0008","type":"II","opinion":"2024-05-30","decision":"2024-07-08","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with non-small cell lung cancer (NSCLC) in combination and as monotherapy for TEVIMBRA, based on results from studies BGB-A317-303, BGB-A317-304, BGB-A317-307 and BGB A317-206. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP Version 2.0 is agreed. In addition, the MAH took the opportunity to correct some figures in section 4.8 with regards to laboratory abnormalities as well as to introduce minor editorial changes to the Product Information."}, {"id":"II/0002","type":"II","opinion":"2024-03-21","decision":"2024-07-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update an existing warning and add ‘Stevens-Johnson Syndrome (SJS)’ and ‘Toxic epidermal necrolysis (TEN)’ to the list of adverse drug reactions (ADRs). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"IAIN/0011/G","type":"IAIN","opinion":"2024-05-16","decision":"2024-07-08","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0010/G","type":"IAIN","opinion":"2024-04-29","decision":"2024-07-08","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0001","type":"T","opinion":"2023-11-17","decision":"2023-12-19","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"} ] }, "tisotumab-vedotin__tivdak": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tivdak-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000344475","type":"IB","opinion":"2026-06-02","decision":null,"affects":["PL"],"codes":["C.11"],"outcome":"accepted","kind":"other","sections":[],"scope":"To submit the results of user testing, following changes to the format and layout of the package leaflet. In addition, the MAH took the opportunity to add local representative contact information to the package leaflet and correct a formatting error in the BG package leaflet."}, {"id":"EMA/VR/0000324286","type":"IB","opinion":"2026-02-23","decision":null,"affects":["Labelling","PL"],"codes":["C.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the PI, Labelling and Package Leaflet which do not alter the meaning of the previously approved wording. Editorial, typographical and stylistic changes are also proposed to the national languages to align with the respective sections in the English version."}, {"id":"EMA/VR/0000264661","type":"IAIN","opinion":"2025-04-28","decision":"2025-06-05","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"EMA/T/0000267043","type":"T","opinion":"2025-05-05","decision":"2025-06-05","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from Pfizer Europe MA EEIG to Genmab A/S"} ] }, "tivozanib-hydrochloride-monohydrate__fotivda": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/fotivda-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [] }, "toremifene__fareston": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/fareston-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"PSUSA/00002999/202309","type":"PSUSA","opinion":"2024-05-30","decision":"2024-07-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - toremifene"}, {"id":"N/0056","type":"N","opinion":"2021-11-24","decision":"2022-01-31","affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IB/0055","type":"IB","opinion":"2021-02-05","decision":"2022-01-31","affects":["SmPC","Annex II","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0050/G","type":"IAIN","opinion":"2018-11-13","decision":"2019-10-29","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00002999/201709","type":"PSUSA","opinion":"2018-05-31","decision":"2018-07-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - toremifene"}, {"id":"IB/0046","type":"IB","opinion":"2017-06-28","decision":"2018-06-12","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0044/G","type":"IAIN","opinion":"2016-08-18","decision":"2016-12-23","affects":["Annex II","PL"],"codes":["B.II.b.2.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0043","type":"IAIN","opinion":"2016-01-14","decision":"2016-12-23","affects":["SmPC"],"codes":["B.II.f.1.a.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Reduction of the shelf life of the finished product - As packaged for sale"}, {"id":"PSUSA/00002999/201409","type":"PSUSA","opinion":"2015-06-25","decision":"2015-08-20","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - toremifene"}, {"id":"IB/0038","type":"IB","opinion":"2014-02-21","decision":"2014-08-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the Package Leaflet based on the results of a User Testing report. The MAH also took the opportunity to update the PI in line with the latest version of the QRD template (9.0)."}, {"id":"N/0036","type":"N","opinion":"2011-01-15","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0032","type":"II","opinion":"2009-01-22","decision":"2009-03-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.3","4.4","4.5","4.8","4.9","5.3"],"scope":"This type II variation concerns the addition of new contraindications in section 4.3 of the SPC and new information in sections 4.4, 4.8, 4.9 and 5.3 of the SPC in relation to a dose-related risk of QTc prolongation following exposure to Fareston. Further, section 4.5 of the SPC has been amended to highlight that Fareston should not be used concurrently with other substances that prolong the QT interval. The Package Leaflet has been updated accordingly. The MAH also took the opportunity to update the annexes in line with the latest QRD template."}, {"id":"N/0031","type":"N","opinion":"2008-05-19","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0030","type":"IA","opinion":"2008-04-30","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"T/0023","type":"T","opinion":"2006-06-02","decision":"2006-07-11","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"R/0022","type":"R","opinion":"2005-11-17","decision":"2006-02-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0021","type":"N","opinion":"2005-03-15","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0019","type":"N","opinion":"2004-07-16","decision":null,"affects":["Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0017","type":"N","opinion":"2003-11-20","decision":"2003-12-22","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0015","type":"N","opinion":"2002-06-17","decision":"2002-07-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0010","type":"II","opinion":"2000-11-16","decision":"2001-03-20","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"R/0011","type":"R","opinion":"2001-01-25","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0008","type":"N","opinion":"1999-11-09","decision":"2000-01-20","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0007","type":"N","opinion":"1999-07-19","decision":"1999-09-07","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0005","type":"N","opinion":"1999-04-19","decision":"1999-06-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0003","type":"II","opinion":"1997-10-19","decision":"1998-03-11","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"T/0001","type":"T","opinion":"1996-06-14","decision":"1996-10-02","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0002","type":"N","opinion":"1996-08-13","decision":"1996-08-14","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"} ] }, "toripalimab__loqtorzi": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/loqtorzi-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000360410","type":"IB","opinion":"2026-07-31","decision":null,"affects":["SmPC","PL"],"codes":["C.z"],"outcome":"accepted","kind":"safety","sections":["6.6"],"scope":"To update sections 2 and 4.4 of the SmPC and section 2 of the PIL to add the statement for Polysorbate 80 in line with the current EC guideline \"Excipients in the labeling and package leaflet of medicinal products for human use\". The MAH also takes the opportunity to update section 6.6 of the SmPC and section 6 of the PIL to remove the reference to the use of 250 mL infusion bag, which is not applicable for clinical practice in Europe and to update section 5 of PIL to amend the terminology for \"use after dilution\". To update section 4 of PIL to remove duplicated side effect, and add clarification for certain side effects to align with SmPC."}, {"id":"EMA/N/0000341695","type":"N","opinion":"2026-05-06","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["6.6"],"scope":"Update to the abbreviations used for the expiry date and batch number in the product labelling, in line with the recommendations set out in QRD Appendix IV. In addition, the minimal particulars for small immediate packaging units have been realigned with the vial label text. Furthermore, local representative details have been added to the package leaflet, along with a correction to text in section 6.6 of the SmPC."}, {"id":"PSUSA/00011094/202506","type":"PSUSA","opinion":"2026-01-29","decision":"2026-03-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - toripalimab"}, {"id":"EMA/VR/0000293928","type":"IAIN","opinion":"2025-09-10","decision":"2026-03-26","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Marketing Authorisation"}, {"id":"EMA/T/0000254154","type":"T","opinion":"2025-03-12","decision":"2025-03-28","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from TMC Pharma (EU) Limited to Topalliance Biosciences Europe Limited"} ] }, "tovorafenib__ojemda": { "source": [], "procedures": [] }, "trametinib__mekinist": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/mekinist-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/mekinist-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000340680","type":"IB","opinion":"2026-05-19","decision":null,"affects":["SmPC","PL"],"codes":["C.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Type IB, To update sections 4.4, Section 4.5, and Section 4.8 of the SmPC, as well as sections 2 and 4 of the Package Leaflet following the final wording agreed in the PRAC recommendation from procedure PSUSA/00010262/202505 (dated 15-Jan-2026), to include the risk of potentiation of radiation toxicity in the product information for Mekinist 0.5 mg and 2 mg Film-coated tablets. In addition, during the linguistic review of procedure Tafinlar-PSUR-0000296502, the Italian Health Authority (AIFA) requested several terminology amendments to the dabrafenib product information. For consistency, the same amendments have been applied to the trametinib product information."}, {"id":"EMA/VR/0000311204","type":"IA","opinion":"2025-11-13","decision":"2026-04-30","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000308071","type":"IAIN","opinion":"2025-11-03","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update Section 4.8 of the SmPC and Section 4 of the PL to implement the signal recommendations on 'Tattoo associated skin reaction (EPITT no 20160)' adopted at the 4 September 2025 PRAC."}, {"id":"EMA/VR/0000278305","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of differentiated thyroid cancer (DTC) for Tafinlar and Mekinist based on primary analysis from pivotal study CDRB436J12301. This is a randomized, double-blind, placebo-controlled phase 3 study to evaluate the efficacy and safety of dabrafenib plus trametinib in previously treated patients with locally advanced or metastatic, radio-active iodine refractory BRAF V600E mutation-positive differentiated thyroid cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the Tafinlar SmPC and sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the Mekinist SmPC are updated. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000271728","type":"II","opinion":"2026-03-26","decision":"2026-04-30","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1"],"scope":"Extension of indication to include treatment of unresectable or metastatic melanoma with a BRAF V600 mutation and adjuvant treatment of Stage III melanoma with a BRAF V600 mutation for adolescents aged 12 years and older for TAFINLAR and MEKINIST, based on an extrapolation report using a modelling and simulation approach to demonstrate PK, PD and efficacy of dabrafenib and trametinib in adolescent patients. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. RMP versions 15.0 and 23.0 for Tafinlar and Mekinist, respectively, have also been submitted."}, {"id":"IAIN/0070/G","type":"IAIN","opinion":"2024-12-04","decision":null,"affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Deletion of manufacturing sites"}, {"id":"IG/1769","type":"IG","opinion":"2024-08-07","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"WS/2647","type":"WS","opinion":"2024-07-25","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8, and 5.1 of the SmPC for Tafinlar and section 5.1 of the SmPC for Mekinist in order to update efficacy and safety information based on final results from study CDRB436F2301 (COMBI-AD); this is a phase 3 randomized double blind study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of high-risk BRAF V600 mutation-positive melanoma after surgical resection. The RMP version 11.1 for Tafinlar and version 19.2 for Mekinist have also been submitted. In addition, MAH took the opportunity to introduce minor editorial changes to the Product Information."}, {"id":"WS/2685","type":"WS","opinion":"2024-05-30","decision":null,"affects":["SmPC"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"WS/2612","type":"WS","opinion":"2024-04-25","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Tumour lysis syndrome and add Tumour lysis syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the review of MAH global database, clinical trials database and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and to introduce editorial changes."}, {"id":"PSUSA/00010262/202305","type":"PSUSA","opinion":"2024-01-25","decision":"2024-03-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trametinib"}, {"id":"IAIN/0060/G","type":"IAIN","opinion":"2023-09-11","decision":"2024-03-18","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Administrative change - Change in the name and/or address of a manufacturer/importer of the finished product, including quality control sites (excluding manufacturer for batch release)"}, {"id":"IG/1710","type":"IG","opinion":"2024-03-07","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"II/0053/G","type":"II","opinion":"2022-07-14","decision":"2023-06-23","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.d","B.II.f.1.e","B.II.d.1.e","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":["6.3","6.4"],"scope":"The SmPC section 6.3 and 6.4 have been updated with 3-years shelf life and storage conditions ‘This medicinal product does not require any special temperature storage conditions.’ (to replace 2-years shelf life in a refrigerator)."}, {"id":"IAIN/0058","type":"IAIN","opinion":"2023-02-24","decision":"2023-06-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update sections 4.4 and 4.8 of the SmPC and sections 2 and 4 of the PL to implement the signal recommendations on `Dabrafenib; trametinib – Haemophagocytic lymphohistiocytosis’ (EPITT no: 19824), adopted at the 12 Jan 2023 PRAC meeting."}, {"id":"WS/2114","type":"WS","opinion":"2021-11-11","decision":"2022-04-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with the final efficacy data from Study BRF113928 (CDRB436E2201), conducted in patients with stage IV BRAF V600 mutant NSCLC, in fulfilment of a post-authorisation measure (REC) from the initial MA."}, {"id":"II/0051","type":"II","opinion":"2022-03-24","decision":"2022-04-29","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of section 4.2 and 5.2 of the SmPC in order to change posology recommendations in hepatic impairment and update pharmacokinetic information based on final results from study MEC116354 listed as a category 3 study in the RMP; this is a Phase I Trial of Single Agent Trametinib (GSK1120212) in Advanced Cancer Patients with Hepatic Dysfunction. The RMP version 18 has also been submitted."}, {"id":"IB/0048/G","type":"IB","opinion":"2021-10-12","decision":"2022-04-29","affects":["SmPC","PL"],"codes":["B.II.c.1.z","B.II.c.1.b","B.II.a.1.a","B.II.c.2.d","B.II.b.1.e","B.II.b.5.a","B.II.b.3.z","B.II.b.2.a","B.II.d.1.c","B.II.d.1.z","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"The finished or intermediate product - Other variation Change in test procedure for an excipient - Other changes to a test procedure (including replacement or addition)"}, {"id":"WS/2070","type":"WS","opinion":"2021-07-22","decision":"2021-08-26","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.1"],"scope":"Update of sections 4.2, 4.4 and 5.1 of the SmPC in order to update the recommendations for the management of pyrexia and to reflect the results of cross comparison clinical studies that used either the existing or updated pyrexia management guidance; the Package Leaflets are updated accordingly. In addition, the WSA took the opportunity to update the list of local representatives and to include minor editorial changes in the Package Leaflets. The requested worksharing procedure proposed amendments to the Summary of Product Characteristics, and Package Leaflet."}, {"id":"WS/2008/G","type":"WS","opinion":"2021-06-03","decision":"2021-07-23","affects":["SmPC"],"codes":["C.I.4","A.6"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 5-years efficacy results from study Phase III study COMBI-AD. This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection in adult patients with a BRAF V600 mutation. Type IA A.6 update of the SmPC with the updated ATC codes released by WHO"}, {"id":"II/0041","type":"II","opinion":"2021-01-14","decision":"2021-07-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","4.6","5.2"],"scope":"Update of sections 4.5, 4.6 and 5.2 of the SmPC in order to add drug-drug interaction information with hormonal contraceptives and to updated relevant part of the SmPC regarding this interaction; the Package Leaflet is updated accordingly. Furthermore, the MAH took the occasion to include the information regarding the sodium content in the products in line with relevant guidelines and to bring the PI in line with the QRD template version 10.1. In addition, the MAH took the opportunity to introduce some editorial changes in the PI and to update the list of local representatives for The Netherlands in the Package Leaflet."}, {"id":"IAIN/0045","type":"IAIN","opinion":"2021-01-11","decision":"2021-07-23","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IAIN/0039","type":"IAIN","opinion":"2020-07-23","decision":"2021-07-23","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"WS/1636/G","type":"WS","opinion":"2019-11-21","decision":"2020-02-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 5-years overall survival (OS) results from study MEK115306 (COMBI-d), a phase III, randomised, double-blinded study comparing the combination of dabrafenib and trametinib to dabrafenib and placebo in first-line therapy for subjects with unresectable or metastatic BRAF V600/K mutation-positive cutaneous melanoma and the 5-years overall survival (OS) results from study MEK116513 (COMBI-v), a phase III, open-label, 2 arm, randomised study comparing dabrafenib and trametinib combination therapy with vemurafenib monotherapy in BRAF V600 mutation-positive metastatic melanoma."}, {"id":"WS/1468","type":"WS","opinion":"2019-02-14","decision":"2020-02-04","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to reflect study results from study BRF117277, a Phase II, Open-Label, Multicentre Study of Dabrafenib plus Trametinib in Subjects with BRAF Mutation- Positive Melanoma that has Metastasized to the Brain (COMBI-MB)."}, {"id":"II/0033","type":"II","opinion":"2019-05-16","decision":"2020-02-04","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.6","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to introduce a warning and new ADRs related to severe cutaneous adverse reactions (SCARs) as per request in the outcome of EMEA/H/C/PSUSA/00010084/201808 for Dabrafenib. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to include some editorial changes in sections 4.4, 4.6 and 4.8 of the SmPC."}, {"id":"R/0029","type":"R","opinion":"2018-12-13","decision":"2019-02-14","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"WS/1274","type":"WS","opinion":"2018-07-26","decision":"2018-08-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.6","4.8","5.1"],"scope":"Extension of indication to include the combination adjuvant treatment with trametinib and dabrafenib of adult patients with stage III melanoma with a BRAF V600 mutation, following complete resection. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 of the Mekinist and Tafinlar SmPCs are updated. The Package Leaflet and the Risk Management plan (version 14.1 for Mekinist and version 9.1 for Tafinlar, according to GVP module V revision 2) are updated in accordance."}, {"id":"WS/1210/G","type":"WS","opinion":"2018-01-25","decision":"2018-04-12","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1","6.4"],"scope":"Update of section 5.1 of the Mekinist (trametinib) and Tafinlar (dabrafenib) SmPC to include the 3-years overall survival (OS) results from study MEK115306 (COMBI-d), a phase III, randomised, double-blinded study comparing the combination of dabrafenib and trametinib to dabrafenib and placebo in first-line therapy for subjects with unresectable or metastatic BRAF V600/K mutation-positive cutaneous melanoma."}, {"id":"T/0025","type":"T","opinion":"2018-03-20","decision":"2018-04-12","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0022","type":"IB","opinion":"2017-10-18","decision":"2018-04-12","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"PSUSA/00010262/201611","type":"PSUSA","opinion":"2017-06-22","decision":"2017-08-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trametinib"}, {"id":"WS/0996","type":"WS","opinion":"2017-02-23","decision":"2017-03-27","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include the combination treatment with trametinib and dabrafenib of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600 mutation. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 5.3 of the Mekinist and Tafinlar SmPC are updated. The Package Leaflet and RMP are updated accordingly. In addition, the Worksharing applicant (WSA) took the opportunity to align the SmPCs of Mekinist and Tafinlar. Furthermore, the Product Information is brought in line with the latest QRD template version 10."}, {"id":"PSUSA/00010262/201511","type":"PSUSA","opinion":"2016-06-23","decision":"2016-08-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trametinib"}, {"id":"II/0013","type":"II","opinion":"2016-02-25","decision":"2016-08-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add Bradycardia and Heart rate decreased as ADRs with a common frequency as a result of clinical studies and post marketing reports. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 9.1."}, {"id":"PSUSA/00010262/201505","type":"PSUSA","opinion":"2016-01-28","decision":"2016-03-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trametinib"}, {"id":"II/0007","type":"II","opinion":"2015-09-24","decision":"2016-03-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","5.3"],"scope":"Update of sections 4.2 and 5.3 of the SmPC in order to update the safety information based on new preclinical data from an oral juvenile toxicity study in rats. Moreover, the consolidated RMP version 12 has been agreed."}, {"id":"II/0006/G","type":"II","opinion":"2015-09-24","decision":"2016-03-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5","5.2"],"scope":"Update of sections 4.5 and 5.2 of the SmPC in order to update the safety information based on new preclinical data provided to fulfil 4 nonclinical Post-Authorisation Measures (REC 001, MEA 004, MEA 005 and MEA 006). Moreover, the consolidated RMP version 12 has been agreed."}, {"id":"IB/0012","type":"IB","opinion":"2015-12-03","decision":"2016-03-22","affects":["SmPC","Labelling","PL"],"codes":["C.I.7.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of - a strength"}, {"id":"WS/0736","type":"WS","opinion":"2015-07-23","decision":"2015-08-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","5.1","5.3"],"scope":"Extension of indication to add a new therapeutic indication for the use in combination of trametinib and dabrafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 5.1, 5.3 of the SmPC are updated. The Package Leaflet was updated accordingly. Furthermore, an updated RMP version X was approved as part of the application."}, {"id":"II/0003","type":"II","opinion":"2015-05-21","decision":"2015-08-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to remove reference to the specific rash management guidelines. The Package leaflet is updated accordingly."}, {"id":"II/0002/G","type":"II","opinion":"2015-07-23","decision":"2015-08-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add warnings regarding Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) and to update the safety information on haemorrhage. The Package Leaflet is being updated to make it in line with the existing pneumonitis information in the SmPC."}, {"id":"IAIN/0009/G","type":"IAIN","opinion":"2015-07-13","decision":"2015-08-25","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"T/0005","type":"T","opinion":"2015-04-07","decision":"2015-04-20","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of MArketing Authorisation from Glaxo Group Ltd. to Novartis Europharm Limited. Transfer of Marketing Authorisation"}, {"id":"II/0001/G","type":"II","opinion":"2014-11-20","decision":"2015-04-20","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Trametinib was phototoxic in an in vitro mouse fibroblast 3T3 Neutral Red Uptake (NRU) assay at significantly higher concentrations than clinical exposures, indicating that there is low risk for phototoxicity to patients taking trametinib. M5 is highly bound to plasma proteins with a free fraction of 1.2%, which is comparable to the free fraction of trametinib at clinically relevant concentrations of 1.4%. The calculated contribution of M5 to the total pharmacological activity is 12%. This is less than the recommended cut-off value of 50%. Therefore, it is agreed that the enzyme(s) and transporter(s) involved in the elimination pathway(s) of M5 do not have to be further investigated."} ] }, "trametinib__spexotras": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/spexotras-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/spexotras-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000340747","type":"IB","opinion":"2026-05-19","decision":null,"affects":["SmPC","PL"],"codes":["C.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8","6.1"],"scope":"Type IB, to update section 4.8 of the SmPC and section 4 of the PL following adoption of PRAC recommendation from procedure PSUSA/00010262/202505 (dated 15-Jan-2026), to include the risk of potentiation of radiation toxicity in the product information for Spexotras 0.05 mg/ml powder for oral solution. In addition, the MAH proposes to align the PI with the EU Excipient Labelling Guideline, the three main components of strawberry flavour (acacia gum, triacetin and artificial flavour) are now included in the Section 6.1 of the SmPC and PL."}, {"id":"EMA/VR/0000308071","type":"IAIN","opinion":"2025-11-03","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"To update Section 4.8 of the SmPC and Section 4 of the PL to implement the signal recommendations on 'Tattoo associated skin reaction (EPITT no 20160)' adopted at the 4 September 2025 PRAC."}, {"id":"EMA/VR/0000293331","type":"IAIN","opinion":"2025-08-28","decision":null,"affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"EMA/VR/0000281571","type":"IB","opinion":"2025-08-20","decision":null,"affects":["SmPC","Annex II","PL"],"codes":["B.II.d.2.d","A.7","B.II.d.1.z","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition); Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*; Change in the specification parameters and/or limits of the finished product - Other changes; Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"WS/2762","type":"WS","opinion":"2025-03-20","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC for Spexotras and update of section 5.2 pf the SmPC for Finlee in order to modify administration instructions and pharmacokinetic properties on food effect based on final results from study CDRB436G2102. This is a randomized, open-label, two independent part, 2 x 2 cross-over study to investigate the relative bioavailability of trametinib and dabrafenib liquid formulations under fasted vs. low-fat low-calorie meal conditions in adult healthy participants. In addition, the MAH took the opportunity to implement editorial changes to the PI."}, {"id":"WS/2693","type":"WS","opinion":"2024-07-18","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8","5.1"],"scope":"Update of sections 4.4, 4.8 and 5.1 of the SmPC in order to add photosensitivity to the list of adverse drug reactions (ADRs) with frequency Common respectively and to update efficacy and safety information on paediatric population based on final results from study CDRB436G2201; this is a phase II open-label global study to evaluate the effect of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive Low Grade Glioma (LGG) or relapsed or refractory High Grade Glioma (HGG). The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes."}, {"id":"WS/2671","type":"WS","opinion":"2024-05-16","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to add ‘Atrioventricular (AV) block’ with an uncommon frequency for Finlee and Spexotras and common frequency for Tafinlar to the list of adverse drug reactions (ADRs), following the PRAC recommendation in the PSUR for Mekinist (PSUSA/00010262/202305). The Package Leaflet is updated accordingly."}, {"id":"WS/2670","type":"WS","opinion":"2024-04-11","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2612","type":"WS","opinion":"2024-04-25","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Tumour lysis syndrome and add Tumour lysis syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the review of MAH global database, clinical trials database and literature. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.3 and to introduce editorial changes."}, {"id":"IG/1769","type":"IG","opinion":"2024-08-07","decision":"2025-05-02","affects":["SmPC","PL"],"codes":["C.I.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Implementation of wording agreed by the competent authority"}, {"id":"IAIN/0010","type":"IAIN","opinion":"2024-12-04","decision":"2025-05-02","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "trastuzumab__herceptin": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/herceptin-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/herceptin-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000313845","type":"IA","opinion":"2025-11-24","decision":null,"affects":["Annex II"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000295324","type":"IB","opinion":"2025-10-17","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update the SmPC and Package Leaflet in line with the Information for the package leaflet regarding polysorbates used as excipients in medicinal products for human use and Excipients in the labelling and package leaflet of medicinal products for human use. The MAH has taken the opportunity to make minor editorial changes in line with the QRD template as well as editorial changes throughout the whole Product Information. In addition, section 6 of the Package Leaflet was updated and the following local representative have been merged: Belgium and Luxembourg, Cyprus and Greece, Ireland and Malta'."}, {"id":"EMA/VR/0000254616","type":"IA","opinion":"2025-04-29","decision":null,"affects":["Annex II"],"codes":["A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)"}, {"id":"IB/0193","type":"IB","opinion":"2024-08-14","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"N/0187","type":"N","opinion":"2023-03-15","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0172","type":"N","opinion":"2021-07-15","decision":"2022-07-08","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0168","type":"II","opinion":"2021-06-10","decision":"2022-07-08","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC (SC formulation) in order to modify the administration instructions by shortening observation time and including mild injection-related symptoms management based on final results from study SafeHER (MO28048) listed as a category 3 study in the RMP; this is a Phase III prospective, two Cohort nonrandomized, multicentre, multinational, open label study to assess the safety of assisted- and self-administered subcutaneous Herceptin as adjuvant therapy in patients with operable HER2- positive early breast cancer. The Package Leaflet is updated accordingly. Additionally, the MAH took the opportunity to introduce minor editorial updates throughout the PI."}, {"id":"IB/0175/G","type":"IB","opinion":"2021-08-20","decision":"2022-07-08","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.z","C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation; Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"II/0160","type":"II","opinion":"2020-07-16","decision":"2021-09-01","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.7","4.8"],"scope":"Update of section 4.7 of the SmPC in order to add “dizziness and somnolence” to the recommendations on the effects on the patient's ability to drive and use machines. Update of section 4.8 of the SmPC to remove Herpes zoster, Erysipelas, Cellulitis Common, Sepsis, Thinking abnormal, Ataxia, Paresis, Brain oedema, Pericarditis, Bradycardia and Hepatic failure as adverse drug reactions."}, {"id":"IB/0169","type":"IB","opinion":"2021-03-24","decision":"2021-09-01","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0156","type":"IB","opinion":"2019-07-27","decision":"2020-09-30","affects":["SmPC"],"codes":["B.II.f.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After first opening (supported by real time data)"}, {"id":"PSUSA/00003010/201809","type":"PSUSA","opinion":"2019-05-29","decision":"2019-07-25","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trastuzumab"}, {"id":"IB/0149","type":"IB","opinion":"2019-03-14","decision":"2019-07-25","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"N/0146","type":"N","opinion":"2018-08-09","decision":"2019-03-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0140","type":"II","opinion":"2018-03-22","decision":"2019-03-11","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.7","4.8","5.1"],"scope":"Update of sections 4.4 and 4.8 of the SmPC for Herceptin 150mg powder for concentrate for solution for infusion and sections 4.4, 4.8 and 5.1 of the SmPC for Herceptin 600mg solution for injection in vial, in order to update the safety information based on the final results from study BO22227 (Hannah) listed as a category 3 study in the RMP; this is a phase III, randomised, open-label study to compare pharmacokinetics, efficacy and safety of subcutaneous (SC) Herceptin with intravenous (IV) Herceptin administered in women with HER2 positive early breast cancer (EBC). Section 4.7 of the SmPC is also updated to reflect Herceptin has minor influence on the ability to drive or use machines."}, {"id":"IB/0144","type":"IB","opinion":"2018-08-23","decision":"2019-03-11","affects":["SmPC","Labelling","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"T/0142","type":"T","opinion":"2018-02-20","decision":"2018-04-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"IB/0139","type":"IB","opinion":"2017-10-27","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Change(s) in the SPC, Labelling or PL intended to implement the outcome of a procedure concerning PSUR or PASS or the outcome of the assessment done under A 45/46 - Other variation"}, {"id":"IB/0136","type":"IB","opinion":"2017-10-30","decision":"2018-03-16","affects":["Annex II"],"codes":["B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IB/0129","type":"IB","opinion":"2017-03-10","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Deletion of a pack size(s)"}, {"id":"N/0114","type":"N","opinion":"2016-05-04","decision":"2017-01-11","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0112","type":"II","opinion":"2016-09-15","decision":"2017-01-11","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["4.9","5.2"],"scope":"Submission of the Heloise (BO27798) final study report. The following changes to the Product Information have been introduced with this variation following a request from the CHMP: Section 4.9 of the SmPC: to mention that a maintenance dose of 10 mg/kg every 3 weeks (q3w) following a loading dose of 8 mg/kg has been studied in a clinical trial with metastatic gastric cancer patients. Section 5.2 of the SmPC: to mention that baseline levels of the shed HER2-ECD receptor observed in metastatic gastric cancer (MGC) patients were comparable to those in metastatic breast cancer (MBC) and early breast cancer (EBC) patients and no apparent impact on trastuzumab clearance was observed."}, {"id":"II/0104","type":"II","opinion":"2016-02-18","decision":"2017-01-11","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in line with long-term efficacy and safety data based on the 10-year follow-up final CSR for Study BCIRG 006. In addition, the MAH took the opportunity to implement editorial changes and to update the annexes in line with the latest QRD template. The provision of the CSR addresses the post-authorisation measure MEA 082.1."}, {"id":"IB/0109","type":"IB","opinion":"2016-02-02","decision":"2017-01-11","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"II/0096","type":"II","opinion":"2015-11-05","decision":"2016-02-22","affects":["Annex II"],"codes":["B.I.a.1.e"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product"}, {"id":"II/0095","type":"II","opinion":"2015-07-09","decision":"2016-02-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0093","type":"II","opinion":"2015-09-24","decision":"2016-02-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0092","type":"II","opinion":"2015-09-24","decision":"2016-02-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0089/G","type":"II","opinion":"2015-04-23","decision":"2016-02-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.5"],"scope":"As requested by the CHMP during the assessment of the variation II-076 and based on the mega population pharmacokinetic analysis, update of section 4.2 (for Herceptin IV only), 4.4, 4.6 and 5.2 to include the key findings. Update of section 4.5 to include the outcomes of the H4613g/GO01305 study and the updated population pharmacokinetic analysis of PK data from BO22227/HannaH study."}, {"id":"II/0084/G","type":"II","opinion":"2015-02-26","decision":"2016-02-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8"],"scope":"Sections 4.2 and 4.8 of the SmPC have been updated with information on switching between intravenous (IV) and subcutaneous (SC) formulations further to safety data from study MO22982. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity make corrections to the SmPC and Package leaflet."}, {"id":"II/0080","type":"II","opinion":"2014-06-26","decision":"2015-02-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.8 of the SmPC in order to add the adverse reactions (ADRs) of stomatitis and palmar-plantar erythrodysaesthesia syndrome with the frequency category of “very common” and to reassign the frequency of existing adverse reactions of the SmPC further to a review of safety information from pivotal clinical studies. Section 4.4 and 4.8 of the SmPC are also updated with regards to the ADRs Interstitial lung disease (ILD), pulmonary hypoplasia and renal hypoplasia reported in the post-marketing setting and currently described in other sections of the SmPC."}, {"id":"II/0078/G","type":"II","opinion":"2014-07-24","decision":"2015-02-06","affects":["SmPC","Labelling","PL"],"codes":["B.II.d.1.a","B.II.d.1.c","B.II.e.1.b.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the specification parameters and/or limits of the finished product - Tightening of specification limits; Change in the specification parameters and/or limits of the finished product - Addition of a new specification parameter to the specification with its corresponding test method; Change in immediate packaging of the finished product - Change in type/addition of a new container - Sterile medicinal products and biological/immunological medicinal products"}, {"id":"II/0074","type":"II","opinion":"2014-02-20","decision":"2015-02-06","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC with the outcomes of the final analysis of efficacy from the Joint Analysis of studies NSABP-B31 and NCCTG N9831. The Package Leaflet is updated accordingly. A statement to avoid confusion with trastuzumab emtansine is added under SmPC section 4.2. Editorial corrections have been made throughout the PI."}, {"id":"II/0069/G","type":"II","opinion":"2013-11-21","decision":"2013-12-18","affects":["Annex II"],"codes":["B.I.a.2.a","B.I.b.2.z","B.I.a.4.b","B.I.a.1.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"New manufacturing site for trastuzumab active substance and changes to the manufacturing process of trastuzumab."}, {"id":"II/0068/G","type":"II","opinion":"2013-11-21","decision":"2013-12-18","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","4.5","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to include the outcomes of the final analysis of 8-year follow-up from Study B016348 (HERA) in adjuvant breast cancer. Update section 4.4 to include a statement on the traceability of Herceptin. Update of sections 4.2, 4.5 and 4.8 to harmonise information from the recent assessment of the subcutaneous formulation of Herceptin. The Package Leaflet is updated accordingly. Editorial changes are proposed throughout the PI. Furthermore, the MAH proposed this opportunity to bring the PI in line with the latest QRD template version 9.0."}, {"id":"X/0060","type":"X","opinion":"2013-06-27","decision":"2013-08-26","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Addition of a new pharmaceutical form \"solution for injection\" for the use of 600mg/5ml (new strength) as subcutaneous use (new route of administration) in the approved breast cancer indications."}, {"id":"II/0062","type":"II","opinion":"2013-01-17","decision":"2013-08-26","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to incorporate information regarding drug-drug interactions (DDI) for Herceptin with various chemotherapeutic agents."}, {"id":"II/0059","type":"II","opinion":"2012-01-19","decision":"2012-02-17","affects":["Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of section 4.6 of the SmPC to include foetal renal growth and function impairment in association with oligohydramnios, in pregnant women who had been exposed to trastuzumab. The Package Leaflet has been updated in accordance. Both SmPC and Package Leaflet were also updated with wording to better reflect the potential for unfavourable outcomes in pregnant cancer patients receiving trastuzumab."}, {"id":"II/0057","type":"II","opinion":"2011-11-17","decision":"2011-12-19","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"The Extension of indication to include treatment of patients with HER2-positive EBC in combination with neoadjuvant chemotherapy, followed by adjuvant trastuzumab monotherapy, for locally advanced (including inflammatory) breast cancer or tumours > 2 cm in diameter."}, {"id":"II/0056","type":"II","opinion":"2011-05-19","decision":"2011-06-23","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Implementation of change(s) requested following the assessment of an USR, class labelling, a PSUR, RMP, FUM/SO, data submitted under Article 45/46, or amendments to reflect a Core SPC - Change(s) with new additional data submitted by the MAH"}, {"id":"II/0053","type":"II","opinion":"2011-03-17","decision":"2011-04-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include concurrent use of Herceptin with chemotherapy in the adjuvant treatment of patients with HER2-positive early breast cancer as part of a treatment regimen consisting of doxorubicin and cyclophosphamide followed by combination with paclitaxel or docetaxel, or as part of a treatment regimen in combination with docetaxel and carboplatin. In addition, the package leaflet has been updated to reflect the results of the user testing further to the assessment of FUM 068."}, {"id":"II/0055","type":"II","opinion":"2010-12-16","decision":"2011-01-27","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Inclusion of additional information in section 4.4 of the SmPC with regard to the risk of Interstitial Lung Disease (ILD) further to the assessment of PSUR 16. Furthermore, the MAH has taken the opportunity to include minor editing changes in the SmPC and package leaflet."}, {"id":"II/0054","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of the recommendations in section 4.6 of the SmPC and section 2 of the Package Leaflet following the review of cases of oligohydramnios in the post-marketing setting. The review was requested further to the assessment of the renewal procedure (R-48)."}, {"id":"II/0051","type":"II","opinion":"2010-09-23","decision":"2010-10-25","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.2"],"scope":"Update of Sections 4.4 and 5.2 of the SmPC to reflect follow up data on clinical pharmacology from a number of pharmacokinetic studies available since the first license renewal."}, {"id":"II/0050","type":"II","opinion":"2010-06-24","decision":"2010-08-06","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.1","5.1"],"scope":"Change to the testing methods used for the determination of HER2 gene amplification in gastric cancer patients to be treated with Herceptin. Sections 4.1 and 5.1 of the SmPC have been updated to broaden the current recommended testing using Fluorescence in situ Hybridisation (FISH) to include Silver-enhanced in situ Hybridisation (SISH). In addition minor editorial changes were included in sections 4.1 and 5.1 of the SmPC."}, {"id":"R/0048","type":"R","opinion":"2010-05-20","decision":"2010-07-28","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0047","type":"II","opinion":"2009-12-17","decision":"2010-01-19","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.4","5.1"],"scope":"Extension of the indication for use in combination with capecitabine or 5-fluorouracil and cisplatin for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease. Herceptin should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay (see Sections 4.4 and 5.1 of the SPC). Editorial changes have been introduced to harmonise information across all indications."}, {"id":"II/0043","type":"II","opinion":"2008-10-23","decision":"2008-12-02","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the type of bags used in the IV administration of Herceptin"}, {"id":"II/0039","type":"II","opinion":"2008-07-24","decision":"2008-09-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SPC with an additional posology of a 3-weekly dosing regimen for patients with metastatic breast cancer following the assessment of a post-approval follow-up measure (FUM038). The package leaflet has been updated accordingly. In addition, the MAH took the opportunity to update the contact details of some local representatives in the package leaflet."}, {"id":"IA/0041","type":"IA","opinion":"2008-01-18","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in BR/QC testing - repl./add. manuf. responsible for BR - not incl. BC/testing"}, {"id":"II/0033","type":"II","opinion":"2007-03-22","decision":"2007-04-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"The MAH applied for an extension of the indication for use in combination with an aromatase inhibitor for the treatment of patients with HER2-positive and hormone receptor positive metastatic breast cancer, not previously treated with trastuzumab. The EMEA website address has also been updated in the Package Leaflet, in accordcance to the latest QRD template."}, {"id":"II/0034","type":"II","opinion":"2007-02-22","decision":"2007-03-09","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Inclusion of Roche Diagnostics GmbH, Mannheim, Germany as a second alternative manufacuter for the finished product and also as a manufacturer responsible for the batch release."}, {"id":"N/0036","type":"N","opinion":"2007-02-12","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0027","type":"II","opinion":"2006-09-21","decision":"2006-10-20","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality changes"}, {"id":"IA/0032","type":"IA","opinion":"2006-09-20","decision":null,"affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer of the finished product"}, {"id":"IB/0031","type":"IB","opinion":"2006-07-31","decision":null,"affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0026","type":"II","opinion":"2006-04-27","decision":"2006-05-22","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":["4.8"],"scope":"Extension of indication for use in patients with HER2 positive early breast cancer. Additionally, the MAH has applied to amend section 4.8 of the SPC to include Stevens-Johnson syndrome, as requested by the CHMP following an assessment of the latest PSUR. The MAH has taken this opportunity to update the annexes to bring them in line with the QRD template. The Package Leaflet has also been updated accordingly."}, {"id":"IA/0023","type":"IA","opinion":"2005-12-01","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"R/0019","type":"R","opinion":"2005-06-23","decision":"2005-09-08","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0018","type":"II","opinion":"2005-05-26","decision":"2005-06-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of the SPC section 5.1 following the 24 months results of study M7701 (Herceptin + docetaxel)."}, {"id":"II/0017","type":"II","opinion":"2005-03-17","decision":"2005-04-28","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"Update of the SPC following the assessment of the 6th PSUR in order to comply to the information on oligohydramnios in section 4.6 and to amend the wording used to describe certain adverse reactions in 4.4 and 4.8 in harmonisation with MedDra terminology ."}, {"id":"IB/0016","type":"IB","opinion":"2004-12-21","decision":null,"affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in shelf-life of finished product - as packaged for sale"}, {"id":"II/0013","type":"II","opinion":"2004-09-16","decision":"2004-10-22","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics"}, {"id":"II/0011","type":"II","opinion":"2004-04-22","decision":"2004-06-10","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of Indication"}, {"id":"N/0012","type":"N","opinion":"2004-05-05","decision":null,"affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0004","type":"II","opinion":"2002-09-19","decision":"2003-01-14","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) to the manufacturing process for the active substance"}, {"id":"II/0002","type":"II","opinion":"2002-03-21","decision":"2002-05-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Summary of Product Characteristics and Package Leaflet"} ] }, "trastuzumab__tuznue": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tuznue-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tuznue-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000355520","type":"IB","opinion":"2026-07-14","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update sections 2, 4.4 and 6.1 of the SmPC, section 3 of the Labeling, and sections 2 and 6 of the PL to include information regarding polysorbates used as excipients in accordance with the Annex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’, following approval of the same change for the reference product. In addition, the MAH has taken the opportunity to remove Kymos Pharma Services, S.L. from the list of manufacturers responsible for batch release in Annex II and the PL, as Kymos is not responsible for batch release. There are no changes to the responsibilities of the manufacturers of Tuznue."}, {"id":"EMA/VR/0000301399","type":"IB","opinion":"2025-10-23","decision":"2026-05-04","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/VR/0000250711","type":"IB","opinion":"2025-02-20","decision":"2026-05-04","affects":["SmPC"],"codes":["B.II.f.1.e","B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the shelf-life or storage conditions of the finished product - Change to an approved stability protocol; Extension of the shelf life of the finished product - Extension of the shelf-life of a biological/ immunological medicinal product in accordance with an approved stability protocol"}, {"id":"EMA/N/0000303396","type":"N","opinion":"2025-10-09","decision":"2026-05-04","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet to introduce a list of local representatives."} ] }, "trastuzumab-deruxtecan__enhertu": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/enhertu-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/enhertu-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000377808","type":"IB","opinion":"2026-10-20","decision":null,"affects":["Annex II"],"codes":["C.9.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"To propose an extension of the deadline from 'Q4 2026' to 'Q2 2027' for the fulfillment of the specific obligation in Annex II.E of the Product Information and of the RMP related to study D967SC00001, Destiny-Lung04 (DL-04)."}, {"id":"EMA/VR/0000322236","type":"II","opinion":"2026-07-23","decision":null,"affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication for Enhertu in combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer, based on the results from the DESTINY-Breast09 study, a phase III study of trastuzumab deruxtecan with or without pertuzumab versus THP (taxane, trastuzumab and pertuzumab) as first-line treatment in patients with HER2-positive, unresectable, or metastatic breast cancer. As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated and the Package Leaflet is updated in accordance. Version 12.0 of the RMP has also been agreed."}, {"id":"EMA/VR/0000340512","type":"II","opinion":"2026-06-25","decision":null,"affects":["SmPC"],"codes":["C.4"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of section 5.2 of the SmPC in order to update biotransformation information based on results from non-clinical studies AE-8104-G (Identification of cytochrome P450 isoforms involved in metabolism of MAAA-1181d) and AE-8795-G (uridine diphosphate-glucuronosyltransferases (UGT) Metabolic stability of MAAA-1181d in Human, Monkey and Rat Liver Microsomes)."}, {"id":"EMA/VR/0000328212","type":"II","opinion":"2026-04-30","decision":"2026-06-25","affects":["SmPC","Labelling","PL"],"codes":["Q.II.f.1.c"],"outcome":"accepted","kind":"other","sections":["6.4"],"scope":"The SmPC section 6.4 has been updated as follows: Store in a refrigerator (2 oC - 8 oC). Do not freeze. Store in the original carton in order to protect from light Section 5 of the Package Leaflet and Annex III.A outer carton are updated accordingly. The Applicant took the opportunity to include the date of the latest renewal in section 9 of the SmPC."}, {"id":"EMA/VR/0000293327","type":"II","opinion":"2026-05-21","decision":"2026-06-25","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumours who have received prior treatment and who have no satisfactory alternative treatment options for Enhertu, based on results from study D967VC00001 (DESTINY-PanTumor02); this is a Phase II, multicenter, open-label study to evaluate the efficacy and safety of trastuzumab deruxtecan for the treatment of selected HER2-expressing tumours; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 11 of the RMP has also been agreed."}, {"id":"EMA/R/0000282648","type":"R","opinion":"2025-09-18","decision":"2025-11-21","affects":["SmPC","Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0048","type":"II","opinion":"2025-02-27","decision":"2025-03-31","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of indication to include treatment of adult patients with unresectable or metastatic HER2-low or HER2-ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment for ENHERTU, based on results from study D9670C00001 (DESTINY-Breast06); this is a phase 3, randomized, multicentre, open-label study of trastuzumab deruxtecan (DS-8201a) compared with investigator's choice chemotherapy in, hormone receptor-positive, HER2-low and HER2-ultralow BC patients whose disease has progressed on endocrine therapy in the metastatic setting."}, {"id":"PSUSA/00010894/202406","type":"PSUSA","opinion":"2025-01-30","decision":"2025-03-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - trastuzumab deruxtecan"}, {"id":"IB/0050","type":"IB","opinion":"2024-10-16","decision":"2025-03-24","affects":["SmPC","PL"],"codes":["B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"IA/0053/G","type":"IA","opinion":"2024-12-02","decision":"2025-03-24","affects":["Annex II"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"II/0040","type":"II","opinion":"2024-01-11","decision":"2024-09-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC based on the final results from studies DS8201-A-J101, DS8201-A-J102, DS8201-A-A103, DS8201-A-A104, DS8201-A-U201, DS8201-A-J202, DS8201-A-J203, DS8201-A-U204, DS8201-A-U205, DS8201-A-U206, DS8201-A-U207, DS8201-A-U301, DS8201-A-U302, and DS8201-A-U303, in order to fulfil MEA 002 (a collection of PK and safety data in at least 10 subjects with moderate hepatic impairment from ongoing Phase 2 or 3 clinical studies) listed as a category 3 activity in the RMP. The updated RMP version 8.0 has also been submitted. In addition, the MAH took this opportunity to introduce editorial changes to the SmPC, annex II.D and the Package Leaflet."}, {"id":"II/0037","type":"II","opinion":"2023-10-12","decision":"2024-09-16","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final clinical study report addendum for study DS8201-A-U303 (DESTINY-Breast04) in order to fulfil the recommendation to submit the final OS analysis. U303 is a phase 3, multicentre, randomised, open-label, active-controlled trial of trastuzumab deruxtecan (T-DXd), an anti-HER2-antibody drug conjugate (ADC), versus treatment of physician’s choice for HER2-low, unresectable and/or metastatic breast cancer subjects."}, {"id":"II/0031","type":"II","opinion":"2023-07-06","decision":"2023-10-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1","5.2"],"scope":"Update of sections 4.8, 5.1 and 5.2 of the SmPC in order to update safety, efficacy and pharmacokinetic information based on data from study DS8201-A-U301 and study DS8201-A-U302. Study U301 was a Phase 3, randomized, 2-arm, open-label, multicenter study designed to compare the safety and efficacy of T-DXd vs TPC in HER2-positive, unresectable and/or metastatic BC subjects who were resistant or refractory to T-DM1."}, {"id":"II/0030","type":"II","opinion":"2023-05-25","decision":"2023-10-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of sections 4.8 and 5.1 of the SmPC in order to update transfusion data for subjects with human epidermal growth factor receptor 2 (HER2)-positive GC or GEJ adenocarcinoma and to update the overall response rate for study DS8201-A-J202 (following the assessment of procedure II/0012) based on studies DS8201-A-J101, DS8201-A-J202 (DESTINY-Gastric01) and DS8201-A-U205 (DESTINY-Gastric02). DS8201-A-J101 is a Phase 1, Two-part, Multicentre, Non-randomised, Open-label, Multiple Dose First-in-Human Study in Advanced Solid Malignant Tumour. DS8201-A-J202 is a Phase 2, Multicentre, Open-label Study of DS-8201a in Subjects with HER2-Expressing Advanced GC/GEJ Adenocarcinoma."}, {"id":"II/0027","type":"II","opinion":"2023-09-14","decision":"2023-10-18","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.8","5.1","5.2"],"scope":"Extension of indication to include the indication treatment of non-small cell lung cancer (NSCLC) for Enhertu (trastuzumab deruxtecan), based on results from study DS8201-A-U206 (DESTINY-Lung02), a phase 2, randomised study evaluating the safety and efficacy of trastuzumab deruxtecan in subjects with HER2-mutated metastatic non-small cell lung cancer. As a consequence, sections 4.1, 4.2, 4.8, 5.1, and 5.2 of the SmPC are updated. The Annex II and Package Leaflet are updated in accordance. Version 7.0 of the RMP has also been submitted."}, {"id":"II/0022","type":"II","opinion":"2022-12-15","decision":"2023-01-23","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or withing 6 months of completing adjuvant chemotherapy; for ENHERTU, based on final results from study DS8201-A-U303 (DESTINY-Breast04). This is a Phase III, multicentre, randomised, open-label, active-controlled trial of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-antibody Drug Conjugate (ADC), versus treatment of physician’s choice for HER2-low, unresectable and/or metastatic breast cancer subjects."}, {"id":"II/0012","type":"II","opinion":"2022-11-10","decision":"2022-12-12","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include monotherapy treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen for Enhertu based on final results from studies DS8201-A-U205 (DESTINY Gastric02) and DS8201 A J202 (DESTINY Gastric01); as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2 of the SmPC are updated. The Annex II and the Package Leaflet is updated in accordance. In addition, changes regarding the dosing recommendation for corticosteroid treatment and the protection of the infusion bag from light have been introduced. Version 3.0 of the RMP has also been submitted."}, {"id":"IB/0026","type":"IB","opinion":"2022-11-10","decision":"2022-12-12","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"R/0023","type":"R","opinion":"2022-09-15","decision":"2022-10-28","affects":["SmPC","Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0019","type":"II","opinion":"2022-07-21","decision":"2022-08-25","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"Update of section 4.2 of the SmPC to add nausea/vomiting premedication prophylaxis information following procedure II/14 based on analyses from Study DS8201-A-U302 (DESTINY-Breast03); this is a Phase 3, multicenter, randomized, open-label, 2-arm, active controlled study in subjects with unresectable and/or metastatic HER2-positive breast cancer previously treated with trastuzumab and a taxane. The Package Leaflet is updated accordingly."}, {"id":"II/0014","type":"II","opinion":"2022-06-23","decision":"2022-07-11","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2","6.6"],"scope":"Extension of indication for Enhertu to include treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 2.0 of the RMP has also been submitted."}, {"id":"IB/0020","type":"IB","opinion":"2022-06-07","decision":"2022-07-11","affects":["SmPC"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"}, {"id":"IB/0017","type":"IB","opinion":"2022-04-22","decision":"2022-07-11","affects":["SmPC","Annex II","PL"],"codes":["B.I.e.5.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Implementation of changes foreseen in an approved change management protocol - For a biological/immunological medicinal product"}, {"id":"IA/0015","type":"IA","opinion":"2022-02-09","decision":"2022-07-11","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"R/0006","type":"R","opinion":"2021-09-16","decision":"2021-11-12","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"IB/0001","type":"IB","opinion":"2021-04-30","decision":"2021-11-12","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - Biological/immunological medicinal product in accordance with an approved stability protocol"} ] }, "trastuzumab-emtansine__kadcyla": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/kadcyla-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/kadcyla-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000348702","type":"IB","opinion":"2026-06-16","decision":null,"affects":["SmPC","PL"],"codes":["C.z"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"To update section 4.6 of the SmPC to clarify the contraception requirements for male patients. The package leaflet is updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes across the product information in line with the latest QRD template. Furthermore, the RMP is updated to (1) provide clarification of male contraception requirements across all relevant sections, (2) remove the Global Enhanced PV Pregnancy Program following the completion of the committed 10-year monitoring period, and (3) update the study status of BO27938 (KATHERINE)."}, {"id":"II/0071/G","type":"II","opinion":"2025-02-20","decision":"2026-02-23","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","A.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"A grouped application consisting of: - C.I.4 (Type II): Update of sections 4.8 and 5.1 of the SmPC in order to update efficacy and safety information based on the interim results from study BO27938 (KATHERINE), a PAES included in annex II.D as well as a category 3 study in the RMP, in order to fulfil ANX 021; This is a randomized, multicentre, open label phase III study to evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy for patients with HER2-positive primary breast cancer who have residual tumour present pathologically in the breast or axillary lymph nodes following preoperative therapy. The Package Leaflet is updated in accordance."}, {"id":"EMA/VR/0000302277","type":"II","opinion":"2026-02-19","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4","B.II.f.1.b.3"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet due to new quality, preclinical, clinical or pharmacovigilance data; Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data)"}, {"id":"N/0067","type":"N","opinion":"2023-03-13","decision":"2023-09-15","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0066/G","type":"II","opinion":"2022-09-08","decision":"2023-09-15","affects":["Annex II","Labelling"],"codes":["B.I.a.1.e","B.I.a.1.f","B.I.c.1.c","B.I.a.4.b"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - The change relates to a biological AS or a starting material [-] used in the manufacture of a biological/immunological product; Change in the manufacturer of AS or of a starting material/reagent/intermediate for AS - Changes to quality control testing arrangements for the AS -replacement or addition of a site where batch control/testing takes place; Change in immediate packaging of the AS - Liquid ASs (non sterile); Change to in-process tests or limits applied during the manufacture of the AS - Addition of a new in-process test and limits"}, {"id":"II/0061/G","type":"II","opinion":"2022-01-27","decision":"2022-07-08","affects":["SmPC"],"codes":["B.I.a.1.j","B.I.b.2.e","B.I.b.1.z","B.II.d.1.z","B.II.d.2.d","B.II.f.1.b.5","B.II.f.1.e","B.I.b.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Test procedure (including replacement or addition) for the AS or a starting material/intermediate Change in test procedure for the finished product - Other changes to a test procedure (including replacement or addition)"}, {"id":"IB/0059/G","type":"IB","opinion":"2021-08-17","decision":"2022-07-08","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.z","C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation; Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"IB/0058","type":"IB","opinion":"2021-07-20","decision":"2022-07-08","affects":["SmPC","Labelling","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0048/G","type":"II","opinion":"2019-12-12","decision":"2020-12-09","affects":["SmPC"],"codes":["C.I.13","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to update the safety information on the risk of Left ventricular dysfunction (LVD) based on the final results from study BO39807 listed as a category 3 study in the RMP. This is an observational study of cardiac events in patients with HER2-positive metastatic breast cancer who have a Left Ventricular Ejection Fraction (LVEF) between 40%-49% prior to initiating treatment with Kadcyla; the RMP version 11.1 is approved. C.I.13: Submission of the final report from study BO28408 listed as a category 3 study in the RMP addressing cardiac safety, safety in elderly patients, and immunogenicity."}, {"id":"II/0045","type":"II","opinion":"2019-11-14","decision":"2019-12-16","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.7","4.8","5.1","5.2","5.3"],"scope":"Extension of indication to include the use of Kadcyla as a single agent for the adjuvant treatment of adult patients with HER2-positive early breast cancer who have invasive residual disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy; as a consequence, sections 4.1, 4.2, 4.4, 4.7, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to introduce editorial changes throughout the product information. An updated RMP version 9.2 has been agreed."}, {"id":"R/0039","type":"R","opinion":"2018-07-26","decision":"2018-09-17","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"T/0038","type":"T","opinion":"2018-02-20","decision":"2018-03-16","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0033","type":"II","opinion":"2017-07-13","decision":"2018-03-16","affects":["Annex II"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Submission of the final clinical study results from study TDM4788g/ BO22589 (MARIANNE) listed as a specific obligation in Annex II.D; this is an interventional randomised, 3-arm, phase III study to evaluate the efficacy and safety of trastuzumab emtansine combined with pertuzumab, or trastuzumab emtansine combined with pertuzumab-placebo versus trastuzumab plus taxane, as first line treatment in HER2-positive progressive or recurrent locally advanced breast cancer or previously untreated metastatic breast cancer. Consequently, Annex II of the product information is updated to remove this study as a specific obligation."}, {"id":"II/0031","type":"II","opinion":"2017-05-11","decision":"2018-03-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"To update the SmPC sections 4.4 and 4.8 to introduce a new warning and a detailed description regarding haemorrhage (not necessarily associated with thrombocytopenia) based on a safety review following the assessment of PSUR 4. The package leaflet is amended accordingly."}, {"id":"N/0024","type":"N","opinion":"2016-05-04","decision":"2017-02-16","affects":["Labelling"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0027/G","type":"II","opinion":"2016-12-15","decision":"2017-02-16","affects":["Annex II"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of the final study report for the study TDM4997g/BO25734 (TH3RESA study) to address the safety concerns in Left Ventricular Dysfunction and Safety in Elderly patients. The RMP and Annex II.D are updated. C.I.11.z (Type IB): To update the RMP following the submission of the third annual report of study H4621g."}, {"id":"II/0019/G","type":"II","opinion":"2016-02-25","decision":"2017-02-16","affects":["SmPC","Annex II"],"codes":["C.I.4","C.I.11.b","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of section 5.1 of the SmPC with long-term Overall survival (OS) data from the pivotal study EMILIA (TDM4370g/BO21977). The Annex II of the product information is updated accordingly to delete the relevant condition (ANX006). Furthermore, section 4.8 of the SmPC is updated as a result of a pooled data analysis from several clinical studies including a change in the frequency of dizziness from very common to common. The RMP is updated accordingly."}, {"id":"II/0020/G","type":"II","opinion":"2015-12-17","decision":"2016-01-22","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4","5.2"],"scope":"Update of sections 4.2, 4.4 and 5.2 of the SmPC in order to update the safety information on hepatic impaired patients after analysis of study BO25499 in fulfilment of MEA 009. The Package Leaflet and the RMP (final version 5.0) are updated accordingly. The due date for final study report for study BO25499 is also changed retrospectively. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 9.1."}, {"id":"IB/0017","type":"IB","opinion":"2015-10-23","decision":"2016-01-22","affects":["SmPC","Annex II","PL"],"codes":["B.II.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Quality change - Finished product - Other variation"}, {"id":"II/0006/G","type":"II","opinion":"2014-10-23","decision":"2015-10-15","affects":["SmPC","Annex II","PL"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.6"],"scope":"The MAh submitted a grouped variation application as follows: - Type II variation to update section 4.6 of the SmPC and section 2 of the Package Leaflet in order to change the duration of contraception to be used after concluding Kadcyla (trastuzumab emtansine) treatment, and the period before starting breast feeding, from 6 to 7 months in line with the Herceptin (trastuzumab) product information."} ] }, "tremelimumab__imjudo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/imjudo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"PSUSA/00011038/202404","type":"PSUSA","opinion":"2024-12-12","decision":"2025-02-14","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tremelimumab PSUSA/11038/202404."}, {"id":"N/0011","type":"N","opinion":"2024-12-11","decision":"2025-02-14","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0008/G","type":"IAIN","opinion":"2024-07-10","decision":"2025-02-14","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"WS/2650","type":"WS","opinion":"2024-04-25","decision":"2024-05-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of section 4.2 and 4.4 of the SmPC in order to simplify current dosing recommendations."}, {"id":"WS/2543","type":"WS","opinion":"2023-12-14","decision":"2024-02-16","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.1","5.2"],"scope":"Update of sections 4.2, 5.1 and 5.2 of the SmPC in order to include paediatric information based on final results from study D419EC00001 “Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or Durvalumab in Combination with Tremelimumab in Pediatric Patients with Advanced Solid Tumors and Hematological Malignancies”. In addition, the MAH took this opportunity to introduce editorial changes."}, {"id":"PSUSA/00011038/202304","type":"PSUSA","opinion":"2023-12-14","decision":"2024-02-16","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tremelimumab"}, {"id":"IG/1659","type":"IG","opinion":"2023-09-04","decision":"2024-02-16","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release"}, {"id":"II/0001","type":"II","opinion":"2023-06-22","decision":"2023-08-04","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":[],"scope":"Extension of indication to include in combination with durvalumab and platinum-based chemotherapy, the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitising EGFR mutations or ALK positive mutations for Imjudo, based on the final analysis from the pivotal study D419MC00004, a Randomised, Multi-center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination with Platinum-Based Chemotherapy for First-Line Treatment in Patients with Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON)."} ] }, "tucatinib__tukysa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/tukysa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/tukysa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000308552","type":"IB","opinion":"2025-11-24","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"EMA/VR/0000258420","type":"IAIN","opinion":"2025-04-03","decision":"2025-09-17","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1","A.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Change in the name and/or address of: a manufacturer (including where relevant quality control testing sites); or an ASMF holder; or a supplier of the active substance, starting material, reagent or intermediate used in the manufacture of the active substance (where specified in the technical dossier) where no Ph. Eur. Certificate of Suitability is part of the approved dossier; or a manufacturer of a novel excipient (where specified in the technical dossier)"}, {"id":"EMA/R/0000262094","type":"R","opinion":"2025-07-24","decision":"2025-09-17","affects":["Annex II","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0023","type":"N","opinion":"2024-10-09","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"T/0021","type":"T","opinion":"2024-07-05","decision":"2024-07-24","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"N/0018","type":"N","opinion":"2024-04-02","decision":"2024-07-05","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0013","type":"II","opinion":"2023-07-20","decision":"2024-07-05","affects":["SmPC","Annex II"],"codes":["C.I.11.b"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to reflect updated efficacy results from study ONT-380-206 (HER2CLIMB), listed as a PAES in the Annex II of the Product Information. This is a phase 2 randomized, double-blinded, controlled study of tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with pretreated unresectable locally advanced or metastatic HER2+ breast carcinoma. The Annex II is updated accordingly."}, {"id":"PSUSA/00010918/202204","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-24","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - tucatinib"}, {"id":"N/0006","type":"N","opinion":"2022-02-11","decision":"2022-06-02","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0002/G","type":"IAIN","opinion":"2021-04-15","decision":"2022-06-02","affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.I.a.2.a","A.5.a","B.I.b.2.a","B.I.a.3.a","A.1","B.II.b.4.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes in the manufacturing process of the AS - Minor change in the manufacturing process of the AS; Administrative change - Change in the name and/or address of a manufacturer/importer responsible for batch release; Change in test procedure for AS or starting material/reagent/intermediate - Minor changes to an approved test procedure; Change in batch size (including batch size ranges) of AS or intermediate - Up to 10-fold increase compared to the originally approved batch size; Administrative change - Change in the name and/or address of the MAH; Change in the batch size (including batch size ranges) of the finished product - Up to 10-fold compared to the originally approved batch size"} ] }, "vandetanib__caprelsa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/caprelsa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/caprelsa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000365370","type":"N","opinion":"2026-08-03","decision":null,"affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives. Additionally, the MAH took the opportunity to introduce minor typographical corrections to the CS, ES and SK package leaflet. Marketing Authorisation"}, {"id":"EMA/VR/0000282298","type":"II","opinion":"2025-11-13","decision":"2026-05-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.6","5.3"],"scope":"Update of sections 4.6 and 5.3 of the SmPC in order to update information regarding fertility and contraception based on published nonclinical data. The Package Leaflet is updated accordingly. observed when untreated females were mated with males treated with vandetanib; however, in the same study there was a slight decrease in the number of live embryos and an increase in preimplantation loss."}, {"id":"EMA/VR/0000246118","type":"II","opinion":"2025-05-22","decision":"2026-05-21","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on ‘Osteonecrosis’ and to add it to the list of adverse drug reactions (ADRs) with frequency not known, based on a safety evaluation report. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor changes to the PI."}, {"id":"EMA/T/0000340014","type":"T","opinion":"2026-04-22","decision":"2026-05-21","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation from Sanofi B.V. to Esteve Pharmaceuticals S.A."}, {"id":"EMA/N/0000224361","type":"N","opinion":"2024-09-06","decision":"2026-05-21","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of the package leaflet with revised contact details of local representatives."}, {"id":"IAIN/0060/G","type":"IAIN","opinion":"2023-08-11","decision":"2024-07-24","affects":["Annex II","PL"],"codes":["B.II.b.2.a","B.II.b.1.a","B.II.b.2.c.2","B.II.d.2.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement/addition of a site where batch control/testing takes place; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Including batch control/testing; Change in test procedure for the finished product - Minor changes to an approved test procedure"}, {"id":"IAIN/0058","type":"IAIN","opinion":"2023-07-11","decision":"2024-07-24","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"PSUSA/00009327/202204","type":"PSUSA","opinion":"2022-11-10","decision":"2023-01-12","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - vandetanib"}, {"id":"II/0043","type":"II","opinion":"2022-09-15","decision":"2022-11-28","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.1","4.2","4.4","5.1"],"scope":"Update of sections 4.1, 4.2, 4.4 and 5.1 of the SmPC to reflect the restriction of the indication for Caprelsa (vandetanib) for the treatment of aggressive and symptomatic RET mutant medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease based on the results of the D4200C00104 study and the re-evaluation of efficacy in RET negative patients from study D4200C00058, both previously listed as a specific obligation in the Annex II; the Package Leaflet is updated accordingly."}, {"id":"II/0052","type":"II","opinion":"2022-04-22","decision":"2022-05-30","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.2","4.4"],"scope":"Update of sections 4.2 and 4.4 of the SmPC in order to amend an existing warning on renal failure based on safety signal evaluation report. In addition, the MAH took the opportunity to update the contact details for local representative in DE in the Package Leaflet."}, {"id":"PSUSA/00009327/202104","type":"PSUSA","opinion":"2021-11-11","decision":"2022-01-11","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - vandetanib"}, {"id":"N/0051","type":"N","opinion":"2021-11-04","decision":"2022-01-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0047","type":"N","opinion":"2020-11-17","decision":"2022-01-11","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0048/G","type":"IA","opinion":"2021-06-04","decision":"2022-01-11","affects":["Annex II","PL"],"codes":["A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites"}, {"id":"N/0038","type":"N","opinion":"2019-06-11","decision":"2020-01-13","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0028","type":"II","opinion":"2019-02-28","decision":"2020-01-13","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of Annex II to modify the specific obligation SOB 001 to ensure that comprehensive data are generated by the agreed due date. The revised RMP version 12.4 is acceptable. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10 and to update the list of local representatives in Package Leaflet."}, {"id":"IG/1003","type":"IG","opinion":"2018-12-20","decision":"2020-01-13","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in the name and/or address of the MAH"}, {"id":"IAIN/0042","type":"IAIN","opinion":"2019-10-30","decision":"2020-01-13","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0030","type":"II","opinion":"2018-02-22","decision":"2019-01-15","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC to add information on overall survival based on the addendum to clinical study report from the study D4200C00058 (cut-off date 2015): An International, Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 versus Placebo in Subjects with Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer. In addition, the Marketing authorisation holder took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"II/0029","type":"II","opinion":"2018-05-31","decision":"2019-01-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC to reflect the results from pre-clinical study titled “ZD6474: A 104 Week Carcinogenicity Study by Oral Gavage in Rats”, study number 521826."}, {"id":"IAIN/0033/G","type":"IAIN","opinion":"2018-10-16","decision":"2019-01-15","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"N/0026","type":"N","opinion":"2017-08-10","decision":"2018-02-09","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IAIN/0024/G","type":"IAIN","opinion":"2016-12-14","decision":"2017-02-17","affects":["Annex II","PL"],"codes":["B.II.b.1.a","B.II.b.1.b","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"II/0016","type":"II","opinion":"2016-11-10","decision":"2016-12-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.5","4.6","4.8","4.9","5.1","5.2"],"scope":"Extension of Indication to include paediatric patients aged 5 to 18 with unresectable locally advanced or metastatic medullary thyroid carcinoma (MTC) for Caprelsa; as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 4.9, 5.1 and 5.2 of the SmPC are updated with efficacy and safety information from studies IRUSZACT0098, ISSZACT0004, IRUSZACT0051 and IRUSZACT0061. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet."}, {"id":"T/0022","type":"T","opinion":"2016-08-15","decision":"2016-09-08","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of marketing authorisation from AstraZeneca AB. to Genzyme Europe B.V. Transfer of Marketing Authorisation"}, {"id":"IB/0019","type":"IB","opinion":"2016-04-26","decision":"2016-09-08","affects":["SmPC","Annex II","PL"],"codes":["C.I.11.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the RMP - Other variation"}, {"id":"PSUSA/00009327/201504","type":"PSUSA","opinion":"2015-11-19","decision":"2016-01-14","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - vandetanib"}, {"id":"II/0011","type":"II","opinion":"2014-10-23","decision":"2015-01-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.3"],"scope":"Update of section 5.3 of the SmPC in order to incorporate the results of a 6-month mouse carcinogenicity study."}, {"id":"II/0004/G","type":"II","opinion":"2013-12-18","decision":"2015-01-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC further to the results of drug-drug interaction studies with digoxin, metformin, antacids (omeprazole or ranitidine) and midazolam, conducted to fulfil additional pharmacovigilance activities (MEA 005, 006, 007 and 008)."}, {"id":"R/0005","type":"R","opinion":"2013-10-24","decision":"2013-12-20","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"R/0002","type":"R","opinion":"2012-12-13","decision":"2013-02-18","affects":["Annex II"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."} ] }, "vemurafenib__zelboraf": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/zelboraf-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/zelboraf-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"IG/1730","type":"IG","opinion":"2024-03-26","decision":null,"affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"PSUSA/00009329/202208","type":"PSUSA","opinion":"2023-04-26","decision":"2023-06-26","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - vemurafenib"}, {"id":"N/0064","type":"N","opinion":"2023-03-14","decision":"2023-06-26","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0060","type":"N","opinion":"2021-11-04","decision":"2022-02-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"N/0059","type":"N","opinion":"2021-08-10","decision":"2022-02-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"IA/0058","type":"IA","opinion":"2021-02-12","decision":"2022-02-18","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"}, {"id":"II/0054","type":"II","opinion":"2019-10-31","decision":"2020-10-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Caution should be used when administering Vemurafenib with strong CYP3A4/PgP inhibitors. Patients co-treated with such agents should be carefully monitored for safety, and dose modifications applied if clinically indicated."}, {"id":"N/0052","type":"N","opinion":"2018-08-09","decision":"2019-02-18","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0048/G","type":"II","opinion":"2018-05-17","decision":"2019-02-18","affects":["SmPC"],"codes":["C.I.4","C.I.13"],"outcome":"accepted","kind":"other","sections":["5.2"],"scope":"Update of the SmPC section 5.2 with the information on mean bioavailability of vemurafenib at steady state together with information on renal elimination based on the phase I study GO28395. Submission of the CSR from the study GO27826: A Phase III, Randomised, Double-Blind, Placebo-Controlled Study of Vemurafenib (RO5185426) Adjuvant Therapy in Patients with Surgically Resected, Cutaneous BRAF-Mutant Melanoma at High Risk for Recurrence. Minor editorial changes have been included in the PI. The RMP version 11.0 has also been updated."}, {"id":"II/0042/G","type":"II","opinion":"2018-03-01","decision":"2019-02-18","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of the SmPC section 4.8 with information on radiation toxicity based on the data from study MO25515 (MEA 006) [An Open-Label, Multicenter Study to Assess the Safety of RO5185426 (Vemurafenib) in Patients with Metastatic Melanoma] Submission of study GP28492 (MEA 010) [ZeSS: A Prospective Observational Safety Study of Patients with BRAFV600 Mutation-positive Unresectable or Metastatic Melanoma Treated with Vemurafenib (Zelboraf)]. The RMP version 10.3 is also submitted."}, {"id":"IB/0050","type":"IB","opinion":"2018-08-14","decision":"2019-02-18","affects":["SmPC","PL"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"T/0047","type":"T","opinion":"2018-02-20","decision":"2018-04-06","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0043","type":"II","opinion":"2018-01-25","decision":"2018-04-06","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC in order to update the safety information following results from pooled safety analysis of the final results from pivotal phase II (NP22657 BRIM-2) and pivotal phase III (NO25026 BRIM-3) trials. The Package Leaflet is updated accordingly. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor changes to the SmPC and Package Leaflet in order to improve clarity and consistency of the information."}, {"id":"PSUSA/00009329/201608","type":"PSUSA","opinion":"2017-03-23","decision":"2017-05-18","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - vemurafenib"}, {"id":"II/0039","type":"II","opinion":"2017-02-23","decision":"2017-05-18","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to include the paediatric clinical data from the Zelboraf NO25390 (BRIM-P) study in conclusion to the assessment of procedure EMEA/H/C/002409/P46/033."}, {"id":"II/0037","type":"II","opinion":"2016-12-15","decision":"2017-05-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to include information on Drug-drug interaction with rifampicin. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the RMP (final version 10.2) and to request modification of MEA 012 part 2 “Study GO29475: Two-part steady-state interaction study with rifampin (3YP3A4 inducer). Furthermore, the MAH is requesting changes of due dates for 3 category 3 final study reports (GO29475 (MEA011), MO25515 (MEA006) and GP28492 (MEA010))."}, {"id":"R/0034","type":"R","opinion":"2016-07-21","decision":"2016-09-22","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"II/0031/G","type":"II","opinion":"2016-04-01","decision":"2016-09-22","affects":["SmPC","Annex II"],"codes":["C.I.4","C.I.11.z"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to add information on Drug-drug interaction of vemurafenib with tizanidine (a CYP1A2 substrate). In addition, the MAH took the occasion to bring the PI in line with the latest QRD template version 10. The RMP (version 10.0) is updated accordingly. Furthermore, the Marketing authorisation holder (MAH) took the opportunity to update the RMP with a proposed new due date for the final clinical study report of study GO28052 and with implementation of the recommendation received during procedure EMEA/H/C/002409/LEG 031 regarding agranulocytosis."}, {"id":"II/0030","type":"II","opinion":"2016-04-01","decision":"2016-09-22","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add safety information on acute kidney injury. The Package Leaflet and the RMP are updated accordingly."}, {"id":"II/0029","type":"II","opinion":"2016-04-01","decision":"2016-09-22","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC with results from study (MO25653) which assessed safety and efficacy of vemurafenib in V600-mutation positive metastatic melanoma patients with previously-treated brain metastases."}, {"id":"II/0025","type":"II","opinion":"2015-09-17","decision":"2015-10-28","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["5.1","5.2"],"scope":"Update of sections 5.1 and 5.2 of the SmPC in order to update the safety information based on the study NP25396."}, {"id":"II/0024/G","type":"II","opinion":"2015-09-24","decision":"2015-10-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5","4.8"],"scope":"Update of sections 4.4, 4.5 and 4.8 of the SmPC in order to update information on the risk of potentiation of radiation toxicity and the risk of progression of pre-existing pancreatic adenocarcinoma with KRAS mutation. The Package Leaflet is updated accordingly."}, {"id":"II/0023","type":"II","opinion":"2015-09-24","decision":"2015-10-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.5"],"scope":"Update of section 4.4 and 4.5 of the SmPC in order to update the Drug-Drug interaction information following finalisation of study GO28394 (A phase I, open-label, multicentre, 3-period, fixed sequence study to investigate the effect of vemurafenib on the pharmacokinetics of a single dose of digoxin in patients with BRAFV600 mutation-positive metastatic malignancy – MEA 013). The RMP has been updated according to the information discussed in the variation. In addition, MAH took this occasion to introduce editorial changes in the SmPC and Package Leaflet."}, {"id":"II/0018","type":"II","opinion":"2015-03-26","decision":"2015-10-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning and the adverse reaction for pancreatitis reported with a frequency “uncommon” further to a cumulative review conducted by the MAH. The Package Leaflet is updated accordingly. The MAH also took the opportunity to make minor editorial changes in the Package leaflet."}, {"id":"IB/0022","type":"IB","opinion":"2015-04-16","decision":"2015-10-28","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0015/G","type":"II","opinion":"2014-06-26","decision":"2014-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC with the new ADR of drug-induced liver injury and a description of liver laboratory abnormalities following a review of pre-clinical studies conducted by the MAH, epidemiologic studies, published literature and the MAH’s safety and clinical database. Section 4.8 is also being updated with neutropenia as a new ADR following treatment with Zelboraf. The PL is being updated accordingly."}, {"id":"II/0014","type":"II","opinion":"2014-02-20","decision":"2014-12-16","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Update of section 4.8 of the SmPC with panniculitis as a new ADR of treatment with vemurafenib with frequency “common” in follow-up to the assessment of the 2nd PSUR. The PL is updated accordingly. The MAH also took the opportunity to make some editorial changes to the SmPC."}, {"id":"II/0011/G","type":"II","opinion":"2013-12-18","decision":"2014-12-16","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of sections 4.4 and 4.8 of the SmPC to include chronic myelomonocytic leukaemia (CMML) and drug reaction with eosinophilia and systemic symptoms (DRESS) as new ADRs based on post-marketing experience. The MAH also took the opportunity to make minor editorial changes. The PL was updated accordingly. The requested group of variations proposed amendments to the Summary of Product Characteristics and Package Leaflet."}, {"id":"II/0010","type":"II","opinion":"2013-10-24","decision":"2013-12-18","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update to section 5.1 of the SmPC with the addition of updated survival data from study NO25026. The MAH took also the opportunity to introduce minor formatting changes to the SmPC. The requested variation proposed amendments to the Summary of Product Characteristics."}, {"id":"II/0008","type":"II","opinion":"2013-05-30","decision":"2013-12-18","affects":["SmPC","PL"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.4"],"scope":"Update of section 4.4 of the SmPC to add a warning with regard to the combined use of vemurafenib and ipilimumab at the CHMP’s request following the results of the clinical trial CA184161. The PL has been updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet with the contact in Croatia."}, {"id":"II/0007","type":"II","opinion":"2013-06-27","decision":"2013-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC to revise the wording on interactions between vemurafenib and BCRP inhibitors at the CHMP’s request following the assessment of MEA 014. The Package Leaflet was updated accordingly. Furthermore, the PI is being brought in line with the latest QRD template version 9.0."}, {"id":"II/0005/G","type":"II","opinion":"2013-01-17","decision":"2013-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.3.b","C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.8","5.1"],"scope":"Update of survival data in section 5.1 of the SmPC, following the assessment of the specific obligation on the updated survival analyses from the pivotal trial NO25026. The obligation in Annex II has been considered fulfilled. In addition, the MAH updated section 4.8 of the SmPC with the adverse drug reacion \"dizziness\" which had been omitted in error. The Package Leaflet has been updated accordingly. Furthermore, the PI is being brought in line with the latest QRD template version 8.2."}, {"id":"II/0003","type":"II","opinion":"2013-01-17","decision":"2013-12-18","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to include safety information following two reports of non-cutaneous squamous cell carcinoma (non-cuSCC) in patients treated with vemurafenib in clinical trials. In addition, the ADR table in section 4.8 was updated with “new primary melanoma” and “QT prolongation”, which had already been reported, in order to include events originating across all trials. Furthermore, the MAH made minor editorial changes to the SmPC to improve consistency throughout by updating table numbers and typographical errors. The PL has been updated accordingly. Furthermore, the PL is being brought in line with the latest QRD template version 8.2."}, {"id":"II/0004","type":"II","opinion":"2012-11-15","decision":"2012-12-20","affects":["SmPC"],"codes":["C.I.3.b"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update the safety information on the inhibition of cytochrome CYP2C8 in vitro. Correction of a minor typographical error was also included. No changes were included in the PL."}, {"id":"II/0002","type":"II","opinion":"2012-11-15","decision":"2012-12-20","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of sections 4.4 and 5.1 of the SmPC with the sequencing results for BRAF V600 for all patients from the pivotal study NO25026 (BRIM-3). The Package Leaflet remains unchanged."}, {"id":"II/0001","type":"II","opinion":"2012-11-15","decision":"2012-12-20","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to include new wording on the posology and the effect of food on the relative bioavailability of vemurafenib as a consequence of the results from the interim analysis of the food-effect study NP25396. The Package Leaflet is updated accordingly."} ] }, "venetoclax__venclyxto": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/venclyxto-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/venclyxto-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000322240","type":"II","opinion":"2026-04-23","decision":"2026-05-27","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include, in combination with acalabrutinib with or without obinutuzumab, the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) for VENCLYXTO based on the results from the pivotal study ACE-CL-311/D8221C00001 (AMPLIFY); this is a randomized, multicenter, open-label, Phase 3 study to compare the efficacy and safety of acalabrutinib (ACP-196) in combination with venetoclax with and without obinutuzumab compared to investigator’s choice of chemoimmunotherapy in subjects with previously untreated chronic lymphocytic leukemia without del(17p) or TP53 mutation."}, {"id":"EMA/VR/0000322237","type":"II","opinion":"2026-04-23","decision":"2026-05-27","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include, in combination with ibrutinib, the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) for VENCLYXTO based on the results of the phase 3 study 54179060CLL3011 (GLOW) and phase 2 study PCYC-1142-CA (CAPTIVATE). GLOW is a randomized, open-label, phase 3 study of the combination of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab for the first-line treatment of subjects with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)."}, {"id":"EMA/VR/0000246380","type":"II","opinion":"2025-07-24","decision":"2026-05-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","4.9","5.2"],"scope":"Update of sections 4.2, 4.9 and 5.2 of the SmPC in order to inform no adjustment is needed in patients with ESRD requiring dialysis and to add information on the pharmacokinetics data for patients with ESRD requiring dialysis, based on final results from study M19-065, “Evaluation of the Pharmacokinetics and Safety of Venetoclax in Subjects with Impaired Renal Function”. The RMP version 10.0 has also been submitted."}, {"id":"IB/0049/G","type":"IB","opinion":"2024-09-20","decision":null,"affects":["SmPC","Annex II","Labelling","PL"],"codes":["B.II.b.2.c.1","B.II.b.1.b","B.II.b.1.a","B.II.e.1.b.1","B.II.e.5.a.2"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing; Replacement or addition of a manufacturing site for the FP - Primary packaging site; Replacement or addition of a manufacturing site for the FP - Secondary packaging site; Change in immediate packaging of the finished product - Change in type/addition of a new container - Solid, semi-solid and non-sterile liquid pharmaceutical forms."}, {"id":"II/0048","type":"II","opinion":"2024-09-05","decision":null,"affects":["SmPC","PL"],"codes":["C.I.3.z"],"outcome":"accepted","kind":"safety","sections":["4.2","4.8","5.1","5.2"],"scope":"Update of sections 4.2, 4.8, 5.1 and 5.2 of the SmPC in order to update safety and efficacy information on paediatric population following the assessment of procedure P46/018 based on final results from study M13-833 - A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies. The Package Leaflet is updated accordingly."}, {"id":"II/0047","type":"II","opinion":"2024-03-21","decision":null,"affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC following submission of the final report from study GO28667 (MURANO) listed as a category 3 study in the RMP. This is a a Multicenter, Phase III, Open-Label, Randomized Study in Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia to Evaluate the Benefit of GDC-0199 (ABT-199) Plus Rituximab Compared with Bendamustine Plus Rituximab."}, {"id":"R/0046","type":"R","opinion":"2023-06-22","decision":"2023-08-11","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"N/0043","type":"N","opinion":"2022-08-19","decision":"2023-02-27","affects":["PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Minor change in labelling or package leaflet not connected with the SPC (Art. 61.3 Notification)"}, {"id":"II/0042","type":"II","opinion":"2022-10-20","decision":"2023-02-27","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update data supporting the efficacy of the combined regimen of obinutuzumab and venetoclax (VEN+G; also known as GDC-0199 or ABT-199) versus obinutuzumab plus chlorambucil (GClb) in previously untreated CLL patients based on final results from study BO25323/CLL14; this is a prospective, open-label, multicenter randomized phase 3 trial to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax (GDC-0199/ABT-199) versus obinutuzumab and chlorambucil in previously untreated patients with CLL and coexisting medical conditions. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI."}, {"id":"IB/0039","type":"IB","opinion":"2022-03-22","decision":"2023-02-27","affects":["SmPC","PL"],"codes":["A.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Other variation"}, {"id":"II/0031","type":"II","opinion":"2021-05-20","decision":"2021-06-21","affects":["SmPC","Annex II","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2"],"scope":"To update venetoclax SmPC wording regarding Tumor lysis syndrome (TLS) prophylaxis and management following an update to the Company Core Data Sheet (CCDS), as well as amendment of the annex II.D to propose additional risk minimisation measures in the form of Patient Card implementation and Direct Healthcare Professional Communication (DHPC) distribution as result of a medical safety assessment conducted on TLS post-marketing reports. The Package leaflet and RMP (version 8) have also been updated, accordingly."}, {"id":"II/0032","type":"II","opinion":"2021-02-25","decision":"2021-05-19","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change(s) in the SPC, Labelling or PL due to new quality, preclinical, clinical or pharmacovigilance data"}, {"id":"II/0030","type":"II","opinion":"2021-04-22","decision":"2021-05-19","affects":["SmPC","Labelling","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.2","4.3","4.4","4.5","4.7","4.8","5.1","5.2"],"scope":"Extension of indication for Venclyxto (venetoclax) in combination with Hypomethylating Agents (HMAs) for the treatment of adult patients with newly-diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. As a consequence, Sections 4.2, 4.3, 4.4, 4.5, 4.7, 4.8, 5.1, 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 6.2 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to make minor corrections in the SmPC."}, {"id":"PSUSA/00010556/201906","type":"PSUSA","opinion":"2020-01-30","decision":"2020-04-08","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - venetoclax"}, {"id":"II/0023/G","type":"II","opinion":"2020-01-30","decision":"2020-03-09","affects":["SmPC","PL"],"codes":["C.I.4","C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.3"],"scope":"Extension of indication to include, in combination with an anti-CD20 antibody (obinutuzumab), treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) for Venclyxto based on the results of the pivotal CLL14/BO25323 phase 3 study; consequently, sections 4.1, 4.2, 4.4, 4.8, 5.1 of the SmPC and corresponding sections of the PL have been revised. The updated RMP version 5.4 has been agreed. Additionally, the SmPC section 5.3 has been updated based on the results of a 4-week dose ranging study, a 6-month carcinogenicity study and two embryo-foetal development (EFD) studies in mice. Minor editorial changes have been introduced throughout the Product Information."}, {"id":"II/0020","type":"II","opinion":"2019-05-29","decision":"2019-06-28","affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["4.2","5.2"],"scope":"Update of sections 4.2 and 5.2 of the SmPC in order to modify posology recommendations in patients with severe hepatic impairment and to reflect the final results of study M15-342 (A Study to Evaluate the Safety and Pharmacokinetics of a Single Dose of Venetoclax in Female Subjects with Mild, Moderate, or Severe Hepatic Impairment) listed as a category 3 study in the RMP; the Package Leaflet is updated accordingly. The RMP version 3.4 has also been submitted."}, {"id":"II/0016","type":"II","opinion":"2018-12-13","decision":"2019-06-28","affects":["SmPC","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":["4.8"],"scope":"Submission of the report from study M13-982 listed as a category 3 study in the RMP. This is a Phase 2 Open-Label Study of the Efficacy of ABT199 (GDC-0199) in Subjects with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia Harboring the 17p Deletion. Following the CHMP request, the MAH has updated SmPC section 4.8 with updated safety data from M13-982 and M14-032 studies. Frequency of following adverse reactions has been upgraded from common to very common: Pneumonia, Lymphopenia, Hyperkalaemia, Hypocalcaemia. The package leaflet has been updated accordingly."}, {"id":"IB/0019","type":"IB","opinion":"2018-10-05","decision":"2019-06-28","affects":["SmPC"],"codes":["B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"}, {"id":"II/0011","type":"II","opinion":"2018-09-20","decision":"2018-11-20","affects":["SmPC","Annex II","PL"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"The Annex II is being updated following the fulfilment of Specific Obligation, which was requested to confirm the efficacy and safety of venetoclax in monotherapy, based on the assessment of interim study report of M14-032. In addition, section 5.1 of SmPC is being updated to reflect the updated results of Study M14-032. The Package Leaflet is updated accordingly. Study M14-032 is: a phase II open-label study investigating efficacy and safety of venetoclax in patients with CLL with relapse or refractory to B-cell receptor signalling pathway inhibitor therapy, listed as a category 2 study in the RMP."}, {"id":"II/0008","type":"II","opinion":"2018-09-20","decision":"2018-10-29","affects":["SmPC","Annex II","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1"],"scope":"Extension of Indication to include Venclyxto in combination with rituximab for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. This submission also fulfils the Annex II condition to submit the results of the MURANO study comparing venetoclax plus rituximab to bendamustine plus rituximab in patients with relapsed/refractory CLL. In addition, RMP version 3.3 (in version 2 of the RMP template) is being approved."}, {"id":"PSUSA/00010556/201712","type":"PSUSA","opinion":"2018-06-28","decision":"2018-08-23","affects":["SmPC"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - venetoclax"}, {"id":"T/0012","type":"T","opinion":"2018-05-30","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Transfer of Marketing Authorisation"}, {"id":"II/0007/G","type":"II","opinion":"2018-03-22","decision":"2018-05-31","affects":["SmPC","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.5"],"scope":"Update of section 4.5 of the SmPC in order to update the drug-drug interaction between venetoclax and digoxin based on final results from study M16-042; this is study to assess the effect of venetoclax on the pharmacokinetics of digoxin in healthy female subjects. Update of section 4.5 of the SmPC in order to update the drug-drug interaction between venetoclax and ritonavir, based on final results from study M15-719; this is study to assess the effect of ritonavir on the pharmacokinetics of venetoclax in healthy female subjects of non-childbearing potential."}, {"id":"IA/0004","type":"IA","opinion":"2017-04-28","decision":"2017-10-30","affects":["SmPC"],"codes":["A.6"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Change in ATC Code/ATC Vet Code"} ] }, "vimseltinib__romvimza": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/romvimza-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [] }, "vismodegib__erivedge": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/erivedge-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/erivedge-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/N/0000304963","type":"N","opinion":"2025-11-04","decision":null,"affects":["Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Update of package leaflet with revised contact details of local representatives and to delete 'United Kingdom (Northern Ireland)' from the list of local representatives in line with the QRD template v10.4’. Additionally, the MAH updated the labelling to implement the change to the prefixes from ‘Batch’ to ‘Lot’ in section '13. Batch number under 'particulars to appear on the outer packaging’ for outer carton and under ‘particulars to appear on the immediate packaging’ for bottle label in the English version."} ] }, "vorasidenib__voranigo": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/voranigo-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000362255","type":"IB","opinion":"2026-08-26","decision":null,"affects":["SmPC"],"codes":["Q.II.f.1.b.5"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Extension of the shelf life of the finished product based on extrapolation of stability data in accordance with relevant stability guidelines"}, {"id":"EMA/VR/0000316249","type":"II","opinion":"2026-04-10","decision":null,"affects":["SmPC","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","4.8"],"scope":"Update of section 4.4 and 4.8 of the SmPC in order to revise the information on hepatotoxicity and add blood bilirubin increased with common frequency, hepatic failure, autoimmune hepatitis, hepatic necrosis, all with uncommon frequency and drug-induced liver injury, and hepatitis acute with a not known frequency to the list of adverse drug reactions (ADRs) based on internal safety signal analyses; the Package Leaflet is updated accordingly. The MAH also took the occasion to update the list of local representative for Finland in the Package leaflet."}, {"id":"EMA/VR/0000323236","type":"IB","opinion":"2026-02-27","decision":null,"affects":["SmPC"],"codes":["B.II.f.1.b.z","B.II.f.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Extension of the shelf life of the finished product - Other variation; Stability - Other variation"} ] }, "zanidatamab__ziihera": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/ziihera-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf"], "procedures": [ {"id":"EMA/VR/0000316398","type":"II","opinion":"2026-05-21","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1","5.2"],"scope":"Update of sections 5.1, and 5.2 of the SmPC in order to update pharmacokinetic information based on final results from study ZW25-ZW1-101 and PopPK analysis. Study 101 is a phase 1 trial of ZW25 in patients with locally advanced (unresectable) and/or metastatic HER2-expressing cancers. In addition, the MAH took the opportunity to introduce editorial changes to the PI."}, {"id":"EMA/VR/0000314733","type":"IB","opinion":"2025-12-17","decision":null,"affects":["SmPC","PL"],"codes":["B.I.d.1.a.4","B.II.f.1.b.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Re-test period/storage period - Extension or introduction of a re-test period/storage period supported by real time data; Extension of the shelf life of the finished product - As packaged for sale (supported by real time data)"} ] }, "zanubrutinib__brukinsa": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/brukinsa-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/brukinsa-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"PSUSA/00010960/202511","type":"PSUSA","opinion":"2026-06-25","decision":"2026-08-31","affects":["SmPC","Labelling"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - zanubrutinib"}, {"id":"EMA/VR/0000303022","type":"IAIN","opinion":"2025-10-29","decision":"2026-07-16","affects":["Annex II","PL"],"codes":["A.5.a"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release"}, {"id":"EMA/R/0000326587","type":"R","opinion":"2026-05-21","decision":"2026-07-16","affects":["SmPC","Annex II","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"renewal","sections":[],"scope":"Renewal of the marketing authorisation."}, {"id":"EMA/VR/0000287519","type":"IAIN","opinion":"2025-08-08","decision":"2025-10-24","affects":["Annex II","PL"],"codes":["A.5.a","A.7"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of a manufacturer/importer of the finished product (including batch release or quality control testing sites) - The activities for which the manufacturer/importer is responsible include batch release; Deletion of manufacturing sites for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place, or supplier of a starting material, reagent or excipient (when mentioned in the dossier)*"}, {"id":"EMA/VR/0000282181","type":"II","opinion":"2025-09-18","decision":"2025-10-24","affects":["SmPC","Annex II","Labelling","PL"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":[],"scope":"Update Annex II to remove the related post-authorisation measure based on final report from study BGB-3111-212, listed as a specific obligation in the Annex II; this is an interventional, Phase 2, open-label, randomized clinical study evaluating the efficacy, safety, tolerability, and PK of zanubrutinib in combination with obinutuzumab in patients with relapsed/refractory follicular lymphoma. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template."}, {"id":"EMA/VR/0000267377","type":"IAIN","opinion":"2025-05-07","decision":"2025-10-24","affects":["SmPC","Labelling","PL"],"codes":["A.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in the name and/or address of the marketing authorisation holder"}, {"id":"EMA/VR/0000253712","type":"IB","opinion":"2025-03-27","decision":"2025-10-24","affects":["Annex II"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"To update Annex IID of the Product Information by revising the due date for the submission of updated safety and efficacy data from study BGB-3111-212, changing it from Q1 2025 to Q2 2025."}, {"id":"X/0023","type":"X","opinion":"2025-06-19","decision":"2025-08-14","affects":["SmPC","Labelling","PL"],"codes":[],"outcome":"accepted","kind":"other","sections":[],"scope":"Annex I_2.(c) Change or addition of a new strength/potency; Annex I_2.(d) Change or addition of a new pharmaceutical form"}, {"id":"IB/0025","type":"IB","opinion":"2024-09-18","decision":"2025-08-14","affects":["Annex II"],"codes":["C.I.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Changes (Safety/Efficacy) of Human and Veterinary Medicinal Products - Other variation"}, {"id":"II/0014","type":"II","opinion":"2023-10-12","decision":"2023-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.4","4.8","5.1"],"scope":"Extension of indication to include in combination with obinutuzumab treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic treatments for BRUKINSA; based on results from studies BGB-3111-212 and BGB-3111-GA101-001. BGB-3111-212 is an ongoing international, Phase 2, open-label, randomized (2:1), active control study of zanubrutinib plus obinutuzumab (Arm A) versus obinutuzumab monotherapy (Arm B) in patients with R/R FL."}, {"id":"II/0013","type":"II","opinion":"2023-05-25","decision":"2023-11-15","affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"safety","sections":["4.4","5.1"],"scope":"Update of section 5.1 of the SmPC in order to update efficacy information based on final efficacy results of ‘progression-free survival’ (PFS) analysis from study BGB-3111-305; this is a Phase III, randomized study of Zanubrutinib compared with Ibrutinib in patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. In addition, the MAH took the opportunity to update section 4.4 of the SmPC in order to align the wording with the approved Package Leaflet."}, {"id":"II/0009","type":"II","opinion":"2023-05-25","decision":"2023-11-15","affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"safety","sections":[],"scope":"Submission of the final report from study BGB-3111-113 - A Drug-Drug Interaction Study of Zanubrutinib with Moderate and Strong CYP3A Inhibitors in Patients With B-Cell Malignancies, listed as a category 3 study in the RMP. The RMP version 3.0 has also been submitted."}, {"id":"IAIN/0017","type":"IAIN","opinion":"2023-09-28","decision":"2023-11-15","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"PSUSA/00010960/202205","type":"PSUSA","opinion":"2022-12-15","decision":"2023-02-09","affects":["SmPC","PL"],"codes":[],"outcome":"accepted","kind":"safety","sections":[],"scope":"Periodic Safety Update EU Single assessment - zanubrutinib"}, {"id":"II/0003","type":"II","opinion":"2022-10-13","decision":"2022-11-15","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.4","4.8","5.1","5.2"],"scope":"Extension of indication to include treatment of adult patients with chronic lymphocytic leukaemia (CLL) for Brukinsa; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.3 of the RMP has also been submitted."}, {"id":"II/0002","type":"II","opinion":"2022-09-15","decision":"2022-10-28","affects":["SmPC","PL"],"codes":["C.I.6.a"],"outcome":"accepted","kind":"indication","sections":["4.1","4.2","4.5","4.8","5.1"],"scope":"Extension of indication to include treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one-prior anti-CD20-based therapy, based on data from 88 patients with R/R MZL from 2 ongoing pivotal studies; Study BGB-3111-214: A Phase 2, open-label, single-arm study designed to evaluate the safety and efficacy of zanubrutinib in patients with R/R MZL, and Study BGB-3111-AU-003: A first-in-human, Phase 1/2, dose-escalation and selection, PK/pharmacodynamic, safety, and efficacy study in adult patients with R/R or treatment-naive B-cell malignancies."}, {"id":"IAIN/0004","type":"IAIN","opinion":"2022-04-29","decision":"2022-10-28","affects":["Annex II","PL"],"codes":["B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"}, {"id":"IAIN/0001/G","type":"IAIN","opinion":"2021-12-21","decision":"2022-10-28","affects":["Annex II","PL"],"codes":["A.7","B.II.b.2.c.1"],"outcome":"accepted","kind":"other","sections":[],"scope":"Administrative change - Deletion of manufacturing sites; Change to importer, batch release arrangements and quality control testing of the FP - Replacement or addition of a manufacturer responsible for importation and/or batch release - Not including batch control/testing"} ] }, "zolbetuximab__vyloy": { "source": ["https://www.ema.europa.eu/en/documents/procedural-steps-after/vyloy-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf","https://www.ema.europa.eu/en/documents/procedural-steps-after/vyloy-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf"], "procedures": [ {"id":"EMA/VR/0000371426","type":"IAIN","opinion":"2026-09-11","decision":null,"affects":["SmPC","PL"],"codes":["C.3.a"],"outcome":"accepted","kind":"safety","sections":[],"scope":"The PL to implement the wording agreed by the PRAC on the signal assessment report on Protein-losing gastroenteropathy (EPITT no 20236). In addition, the contact details for the local representatives are updated in the PL."}, {"id":"EMA/VR/0000293346","type":"II","opinion":"2026-01-22","decision":null,"affects":["SmPC"],"codes":["C.I.13"],"outcome":"accepted","kind":"other","sections":[],"scope":"An analytical method for measuring neutralizing antibodies (NAb) was validated and the results were summarized based on a pooled analysis of data from the 2 phase 3 clinical studies, SPOTLIGHT and GLOW, in order to address a post-approval Recommendation."}, {"id":"II/0005","type":"II","opinion":"2025-06-19","decision":null,"affects":["SmPC"],"codes":["C.I.4"],"outcome":"accepted","kind":"other","sections":["5.1"],"scope":"Update of section 5.1 of the SmPC in order to update immunogenicity data based on the validation report for the new method (8951-ME-0016) to replace the method originally used to test ADA samples from the pivotal studies SPOTLIGHT and GLOW. In addition, the MAH took the opportunity to introduce minor formatting changes to the PI."}, {"id":"II/0006/G","type":"II","opinion":"2025-02-13","decision":null,"affects":["SmPC","Labelling","PL"],"codes":["B.II.e.5.c","B.II.b.3.c"],"outcome":"accepted","kind":"other","sections":[],"scope":"Change in pack size of the finished product - Change in the fill weight/fill volume of sterile multidose (or single-dose, partial use) parenteral medicinal products, including biological/immunological medicinal products; Change in the manufacturing process of the finished or intermediate product - The product is a biological/immunological medicinal product and the change requires an assessment of comparability"}, {"id":"IB/0002/G","type":"IB","opinion":"2025-01-07","decision":null,"affects":["SmPC","PL"],"codes":["B.II.f.1.b.3","B.II.z"],"outcome":"accepted","kind":"other","sections":[],"scope":"Stability of FP - Extension of the shelf life of the finished product - After dilution or reconstitution (supported by real time data); Quality change - Finished product - Other variation"} ] } } }