PRAC Recommendations on Safety Signals

AIFA Drug Safety Signals

Published January 6th, 2026

Detected March 13th, 2026

Summary

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) has adopted recommendations on safety signals discussed in November 2025. Marketing Authorisation Holders (MAHs) are required to provide supplementary information or update product information based on these recommendations, with specific deadlines for certain signals.

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What changed

The European Medicines Agency (EMA) has published recommendations from the Pharmacovigilance Risk Assessment Committee (PRAC) meeting held November 24-27, 2025, concerning various safety signals. These recommendations are directly actionable by Marketing Authorisation Holders (MAHs) for both Centrally Authorised Products (CAPs) and Nationally Authorised Products (NAPs). For specific signals, such as increased risk of brain oedema with Axicabtagene ciloleucel and Lisocabtagene maraleucel, and congenital megacolon with Ponatinib, MAHs are requested to submit supplementary information by February 5, 2026.

MAHs must ensure their product information is kept up-to-date with current scientific knowledge, including these PRAC recommendations. For CAPs, recommendations for product information updates have been agreed by the Committee for Medicinal Products for Human Use (CHMP). For NAPs, National Competent Authorities will oversee adherence. MAHs are referred to EMA guidance for procedural aspects and must use the relevant EPITT reference numbers in communications. Failure to comply could lead to regulatory action and impact product authorization.

What to do next

Review PRAC recommendations for safety signals adopted in November 2025.
Submit supplementary information by February 5, 2026, for specified signals (e.g., Axicabtagene ciloleucel, Lisocabtagene maraleucel, Ponatinib).
Ensure product information is updated in line with PRAC recommendations and relevant regulatory procedures.

Source document (simplified)

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands An agency of the European Union Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2025. Reproduction is authorised provided the source is acknowledged. 6 January 2026 Pharmacovigilance Risk Assessment Committee (PRAC) Adopted at the 24-27 November 2025 PRAC meeting This document provides an overview of the recommendations adopted by the Pharmacovigilance Risk Assessment Committee (PRAC) on the signals discussed during the meeting of 24-27 November 2025 (including the signal European Pharmacovigilance Issues Tracking Tool [EPITT] reference numbers). PRAC recommendations to provide supplementary information are directly actionable by the concerned marketing authorisation holders (MAHs). PRAC recommendations for regulatory action (e.g. amendment of the product information) are submitted to the Committee for Medicinal Products for Human Use (CHMP) for endorsement when the signal concerns Centrally Authorised Products (CAPs), and to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for information in the case of Nationally Authorised Products (NAPs). Thereafter, MAHs are expected to take action according to the PRAC recommendations. When appropriate, the PRAC may also recommend the conduct of additional analyses by the Agency or Member States. MAHs are reminded that in line with Article 16(3) of Regulation No (EU) 726/2004 and Article 23(3) of Directive 2001/83/EC, they shall ensure that their product information is kept up to date with the current scientific knowledge including the conclusions of the assessment and recommendations published on the European Medicines Agency (EMA) website (currently acting as the EU medicines webportal). For CAPs, at the time of publication, PRAC recommendations for update of product information have been agreed by the CHMP at their plenary meeting (8-11 December 2025) and corresponding variations will be assessed by the CHMP. For nationally authorised medicinal products, it is the responsibility of the National Competent Authorities (NCAs) of the Member States to oversee that PRAC recommendations on signals are adhered to. Variations for CAPs are handled according to established EMA procedures. MAHs are referred to the available guidance. Variations for NAPs (including via mutual recognition and decentralised procedures) are handled at national level in accordance with the provisions of the Member States. Expected publication date. The actual publication date can be checked on the webpage dedicated to PRAC recommendations on safety signals. The relevant EPITT reference number should be used in any communication related to a signal.

Page 2/3 The timeline recommended by PRAC for submission of variations following signal assessment is applicable to both innovator and generic medicinal products, unless otherwise specified. For procedural aspects related to the handling of PRAC recommendations on signals (e.g. submission requirements, contact points, etc.) please refer to the Questions and Answers on signal management.

Page 3/3 1. Recommendations for update of the product information Not applicable 2. Recommendations for submission of supplementary information INN Signal (EPITT No) PRAC Rapporteur Action for MAH MAH Axicabtagene ciloleucel; lisocabtagene maraleucel Increased risk of brain oedema in primary mediastinal large B-cell lymphoma (PMBCL) patients (20224) Karin Erneholm (DK) Supplementary information requested (submission by 5 February 2026) Kite Pharma EU B.V., Bristol- Myers Squibb Pharma EEIG Ponatinib Congenital megacolon, maternal exposure during pregnancy (20231) Mari Thörn (SE) Supplementary information requested (submission by 5 February 2026) Incyte Biosciences Distribution B.V. Valproate and related substances Neurodevelopmental disorders with paternal exposure (20191) Liana Martirosyan (NL) Supplementary information requested (submission by 11 March 2026) Sanofi Venlafaxine Cardiotoxicity (20230) Karin Bolin (SE) Supplementary information requested (submission by 13 April 2026) Viatris Limited 3. Other recommendations INN Signal (EPITT No) PRAC Rapporteur Action for MAH MAH Desogestrel; etonogestrel Meningioma (20167) Karin Bolin (SE) No action for MAHs at this stage Not applicable Valproic acid, sodium valproate, valproate semisodium, valpromide