ERA at TOPRA 2025: Session 4 – Human – Revision of the EU variation Regulation

The EU variation Regulation was updated in March 2024 and the new Detailed guideline for classification of variations [last dated from 2008, last update 2013] was published this month.

Nevertheless, this is the first step, limited by the current legislation, and a second step is awaited after the new EU general pharmaceutical regulation is in force (expected 2028).

The current European Commission updates simplify the requirements and procedures, modernise the framework, adapt the rules for grouping and work-sharing, adapt the classification for some products, reduce administrative burden, and implement a risk-based approach.

This session presented an overview of the original goals of the revision, the new changes in the management of post-approval changes; including a comparison of the previous and proposed classifications with statistics and impact for both regulators and industries in term of volume of variations being generated.

The session discussed opportunities to continue re-inventing both submission policies and processes for post-approval changes in the EU for centrally and nationally registered products.

Points to note:

• Second revision will come with implementation of new Directive ~ 2028 and will aim to reduce the number of Type IA variations 
• Reinforcement of Annual Reporting and now mandatory worksharing (e.g. Update RMP, ASMFs, CEPs, etc.) discussed
• Supergrouping can now include NAPs and Type IA variations
• Worksharing (WS) now includes CAP, MR/DC and NAPs. New Declaration in eAF. Letter of Intent required.
• MEB have seen significantly increased in WS applications. MEB is seeing a decline in IB variations already. Supergrouping applications have also increased in NL. 
• EMA Q&As are being compiled and will be published in Q4 2025 (e.g. Stability testing, classification of changes, skip/periodic testing, PLCM, etc.). More Q&As planned for Q1 2026
• SPOR (referential lists) and eAF/PLM updates to follow
• EMA encourages the use of the Change Management Protocol and hope to see it used more in future
• Mandatory worksharing should be useful for both industry and Regulators, to increase efficiency and get faster approvals for multiple MAs
• EMA allows the grouping of related IA and IAin despite the fact that variation regulation does not technically allow this (and it is not allowed for MR/DC), new guidance should help to clarify
• Article 5 recommendations will remain as an option for variations that are not included in the new regulation
• ICH Q12 should be reviewed in conjunction with new regulation and guidance

Written by

Alice D’Alton