Guidance on the application of the revised variations framework

Following the revision of the Variation Regulation applicable since 1 January 2025, the European Commission (EC) has now published a draft version of the new EC guidelines on the details of the various categories of variations and operation of the procedures.

The EC expects these guidelines to apply from 15 January 2026, as provided in the published draft version of the Variations Guidelines.

Please note that these draft guidelines are not final. They are without prejudice to the finalised versions that will be published in the Official Journal.

VARIATIONS FRAMEWORK

Variations Regulation

The revised Variations Regulation applies since 1 January 2025 for variation applications implemented and submitted to the European Medicines Agency (EMA) from 1 January 2025.

Variations Guidelines

A single cut-off date for the entry into application (i.e., 15 January 2026) is foreseen as set out in the draft version of the Variations Guidelines.

Until 15 January 2026, marketing authorisation holders should continue to rely on the current Variations Guidelines and on the specific procedural guidance.

To find procedural guidance on both the Variations Regulation and current Variations Guidelines, see EMA and the Heads of Medicines Agencies (HMA) websites:

 

IMPLEMENTATION OF THE VARIATIONS FRAMEWORK

Marketing authorisation holders (MAHs) and national competent authorities should follow certain principles to facilitate a smooth transition to the new variations framework.

Type-IB and II variations (including grouped Type-IA variations)

For Type-IB and / or Type-II variations submitted before 15 January 2026: 

  • These types of variations will follow the current Variations Guidelines until the procedure is completed (even if completed after 15 January 2026).
  • MAHs should use the current electronic application form (eAF) version for these submissions.

For Type-IB and Type-II variations submitted as of15 January 2026: 

  • These types of variations will follow the new Variations Guidelines.
  • MAHs should use the updated eAF version for these submissions.

Type-IA variations

The date of implementation of the change(s) in the quality management system of the marketing authorisation holder (MAH) should be taken as the point of reference for the application of the current/new Variations Guidelines (rather than the date of submission used for type IB/II variations).

To facilitate the transition for Type IA variations and minimise the overlap of the two systems the rules stated below should apply.

  • For all Type-IA variations implemented before 15 January 2026 should be submitted before 15 January 2026 using the current electronic application form (eAF) version. 

    If no annual update is due before 15 January 2026, the MAH should submit said implemented variations preferably as an earlier annual update submission or otherwise as individual notifications outside the annual update.

  • For all Type-IA variations implemented as of 15 January 2026, the first type-IA variation implemented as of 15 January 2026 will start a new cycle for the annual update, unless one of the listed annual update exemptions applies to that variation.

All variations

For any variations submitted before 15 January 2026:

  • The new variation classification categories and the updated electronic application form (eAF) cannot be used in anticipation of the entry into application of the new Variations Guidelines.
  • Any variations submitted before 15 January 2026 using the updated eAF version and / or a new variation category will not be validated and the marketing authorisation holder (MAH) will have to revise its application.

For any variations submitted and implemented as of 15 January 2026: 

  • MAHs should use the updated eAF version. The updated eAF will be published before 15 January 2026 to enable MAHs to prepare applications planned for submission after 15 January 2026.

EMA and CMDh will publish more guidance regarding the implementation of the new variation categories.

Stakeholders should monitor the webpages on EMA and HMA websites mentioned at the Variations framework section. They should also take the necessary measures to prepare their systems, processes, procedures and documentation for compliance with the revised variation framework.

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. It became applicable on 1 January 2025.

This regulation revised the 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.

It will be further complemented by the new EC Variations guidelines that is expected to become applicable from 15 January 2026.

The current 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, until 14 January 2026 (included).

The new draft Variations Guidelineson the details of 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 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use, and on the documentation to be submitted pursuant to those procedures, is expected to become applicable from 15 January 2026.