The European Commission has published new Guidelines on the details of the various categories of variations (to the terms of marketing authorisations ("MA") for medicinal products) ("Variations Guidelines").
The new 2025 Variations Guidelines replace the older 2013 Variation Guidelines, and support the implementation of the amended Regulation (EC) No 1234/2008 ("Variations Regulation") (see our BioSlice blog post), which entered into force in January 2025. The Variations Guidelines provide detailed guidance for marketing authorisation holders ("MAH") on modifying and updating their MAs, the procedures to follow and the related requirements.
Overall, the new Guidelines provide greater flexibility and clarity in certain aspects of the variation procedures. At the same time, they introduce new obligations for MAHs that should be taken into account by pharmaceutical companies going forward.
In this blog, we highlight some of the key changes introduced by the Variations Guidelines.
1. Submission requirements and timelines
- Variation applications must now be submitted electronically through the EMA e-submission portal
- Extension applications must be submitted "simultaneously" to all relevant authorities, (whereas this was not explicitly specified under the 2013 Guidelines)
- The estimated timetable for the assessment of Type II variations is not specified in the Guidelines, and MAHs and EU Member States concerned are only informed of these by the reference authority (i.e. European Medicines Agency ("EMA") or National Competent Authorities ("NCA") of the EU Member State chosen by the MAH, depending on whether centrally or nationally authorized medicinal products are involved) at the start of the procedure
2. Worksharing procedure
- Following the Worksharing Procedure (i.e. procedure that allows submitting several Type IB or Type II variations in a single application) is now mandatory where the same Type IB or Type II variation, or the same group of variations, affects multiple MAs of the same MAH
- Following the Worksharing Procedure is optional (if justified and agreed by the EMA or the relevant NCA) where variations including at least one Type IB or Type II variation, that do not contain any extension, are related to multiple MAs owned by different MAHs across several EU Member States (Previously, worksharing was optional only for variations not containing extensions that related to MAs of the same MAH)
- The assessment timetable for the worksharing procedure now follows the highest type of variation among the variations to be submitted. The estimated timetables are not specified in the Guidelines, and MAHs and EU Member States concerned are only informed of these by the reference authority (i.e. EMA or the NCA of the Member State chosen by the MAH, depending on whether the worksharing involves centrally or nationally authorized medicinal products) at the start of the procedure
3. Grouping and super-grouping
- For centralised MAs, several Type IA variations no longer need to be identical to be submitted as a single notification (The 2013 Guidelines required the Type IA variations to be identical)
- Super-grouping allows MAHs to submit several Type IA variations involving multiple MAs from the same MAH across one or more EU Member States in a single submission
- The EMA or the Co-ordination Group for Mutual Recognition and Decentralised procedures ("CMDh") may, where justified, publish cases accepting related changes to be submitted in a single submission without formal grouping, although it is unclear what this means in practice
4. Safety-related and quality variations
- Safety-related Type II variations must now be implemented immediately (Under the 2013 Guidelines implementation had to be done "within a timeframe agreed between the [European] Commission and the MAH")
- In case of changes to the therapeutic indication, posology or maximum daily dose, the quality documentation must be reviewed by the MAH, and any resulting changes to the quality documentation (e.g. changing impurity limits) require submitting a quality variation
5. Vaccines and public health emergencies
- The fast-track procedure available to the human influenza vaccine is now also available for the human coronavirus vaccines. The EMA will define the procedure and timelines for this procedure
- Variations to active substances of authorised influenza, coronavirus, or other vaccines with potential to address a public health emergency in the EU are classified as Type II variations. MAHs are advised to discuss the submissions of the variations with the EMA or NCAs in advance
6. Classification and documentation requirements
- The Annex of the Guidelines has been expanded to include more detailed categories for variation types (e.g. related product lifecycle management document ("PLCM"), not mentioned under the 2013 Guidelines)
- Changes have been made to the documentation requirements for certain categories (e.g. changes to the active substance, excipient, or medical device part now require proof of amendment to the relevant dossier section)
- Unclassified variations submitted as Type II now require submitting a detailed justification (The 2013 Guidelines required this only for Type IB)
What's next
The Guidelines will apply to variation submissions from 15 January 2026. We recommend MAHs to review their internal processes, policies and procedures to ensure compliance with the new obligations, while also taking advantage of the streamlined procedures (e.g. super-grouping).
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
