Guidance on the application of the amended Variations Regulation from 1 January 2025

Guidance is available on the implementation of the amended Variations Regulation (EU) 2024/1701 for variation applications implemented and submitted from 1 January 2025.

This guidance provides instructions on the implementation of the amended Variations Regulation applicable as of 1 January 2025 that includes amendments to the Article 5 procedure, on the annual update for minor variations of type IA, on the procedure for grouping and super-grouping of Type IA variations, on the annual update of a human influenza or human coronavirus vaccine, on the mandatory (same MAH) and voluntary (differentMAHs) use of the work sharing procedure, on variations to human vaccines for public health emergencies and to the Annexes.

The European Commission is also currently reviewing the guidelines on the details of the various categories of variations and operation of the procedures (Variations guidelines: Proposed amendments to the European Commission guidelines on variations categories and procedures) and an updated version is expected during 2025.

During this transition period, from 1 January 2025 and until the updated Variation Guidelines become applicable, marketing authorisation holders (MAHs) should continue to rely on the current classification part of the Variations Guidelines and on specific procedural guidance that is available here below and on the EMA website. 

Stakeholders are invited to monitor the CMDh and EMA websites and to take the necessary measures to prepare their systems, processes, procedures and documentation for compliance with the upcoming framework.

Variation applications submitted before 1 January 2025 will still follow the current provisions as defined in Regulation (EC) No 1234/2008 as amended by Commission Delegated Regulation (EU) 2021/756 until their conclusion. 

In case of doubt, MAHs should contact the relevant competent authority.

Legal framework

Regulation (EU) 2024/1701 of 11 March 2024 amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use (Variation Regulation) has entered into force on 7 July 2024. 

This regulation revised the current rules setting out the procedures for post-authorisation changes to a marketing authorisation to make the lifecycle management of medicines for human use more efficient and future-proof.

Variations Guidelines include details on the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008. This concerns the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures (OJ C 223, 2.8.2013, p. 1–79).

Guidance applicable from 1 January 2025

• Best Practice Guides (BPGs) for the Submission and Processing of Variations in the Mutual Recognition Procedure

  Chapter 1: CMDh BPG for the Allocation of the Mutual Recognition Variation Number for Type I Notifications, Type II Variations, Grouping and Worksharing (October 2024) [Track version]

  Chapter 2: Procedure for Automatic Validation of Mutual Recognition Procedures for Variations (October 2024) [Track version]

  Chapter 3: CMDh BPG for the Processing of Type IA Minor Variations (Notifications) in the Mutual Recognition Procedure (October 2024) [Track version]

  Chapter 4: CMDh BPG for the Processing of Type IB Minor Variations (Notifications) in the Mutual Recognition Procedure (October 2024) [Track version]

  Chapter 5: CMDh BPG for the Handling of Type II Variations in the Mutual Recognition Procedure (October 2024) [Track version]

  Chapter 6: CMDh BPG for the Processing of (Super-)Grouped Applications in the Mutual Recognition Procedure (October 2024) [Track version]

  Chapter 7:  CMDh BPG on Variation Worksharing (October 2024) [Track version]

  Chapter 8: CMDh BPG on CMDh Recommendations on Unforeseen Variations (October 2024) [Track version]

• EMA/CMDh Explanatory notes on variation application form (Human medicinal products only) (October 2024) [Track version]

• Examples for acceptable and not acceptable groupings for MRP/DCP products (October 2024) [Track version]

• Position paper common grounds seen for invalidation/delaying day 0 for variations (October 2024) [Track version]

• Q&A - List for the submission of variations for human medicinal products according to Commission Regulation (EC) 1234/2008  (October 2024) [Track version]

• Template Cover letter for the submission of variation applications in the MRP (October 2024) [Track version]

• Template Letter of Intent for the submission of a type IA super-grouped procedure to the reference authority according to Article 7a of Commission Regulation (EC) No 1234/2008 (October 2024) [Track version]

• Template request for a recommendation on the classification of an unforeseen variation under Article 5 of Commission Regulation (EC) No 1234/2008 (October 2024) [Track version]

• Urgent Safety Restriction Member State Standard Operating Procedure (October 2024) [Track version]