Proposed changes to the European Commission guidelines on variations categories and procedures (2013/C 223/01)

Background

The European Commission is reviewing the rules governing procedures for post-authorisation changes to the terms of a Marketing Authorisation (MA) for human medicines.

This involves amendments to Regulation (EC) No 1234/2008 (Variations), specifically by Regulation (EC) No 2024/1701, as well as updates to the guidelines on variation categories and the operation of relevant procedures (Variations Guideline 2013/C 223/01).

The proposed amendments aim to future-proof and improve the efficiency of lifecycle management for medicinal products in the European Union. It is anticipated that the updated variation guidelines will come into effect during 2025.

Summary of the proposed changes

Removal of references to veterinary medicinal products - Following the adoption of new legislation on veterinary medicines (applicable since 28 January 2022), references to veterinary products have been removed.

The legal framework for veterinary products is now governed by Regulations (EU) 2019/4, 2019/5, 2019/6, and (EC) 726/2004.

Consolidation of variation review guidance - The guideline has been updated to combine guidance for purely national and mutual recognition/decentralised procedures across variation Types IA, IB, and II.

This change is intended to reduce assessor workload and encourage proactive variation planning by companies.

Super-grouping of Type IA variations (Section 2.1.1) - A group of Type IA variations may now be submitted in a single notification, even across multiple MAs held by the same MAH, provided the variations are identical. This supports more efficient assessment by health authorities.

Annual update of Type IA variations - Variations not requiring immediate notification can be collected and submitted as an annual update, part of a grouping, or a super-grouping.

Health authorities will no longer expect single Type IA submissions. Exceptions may apply, e.g., when changes affect product information included in Certificates of Pharmaceutical Products (CEPs), necessitating earlier submission.

Mandatory use of the worksharing procedure (Section 3.0) - The guidance now mandates the use of worksharing where applicable. Applicants must plan in advance, including requesting procedure numbers and a Reference Member State.

Early implementation shows companies adopting this approach for CMC submissions that previously required individual national submissions.

Flexibility for vaccines addressing public health emergencies - Section 2.5 now includes updated guidance for annual updates relating to human coronavirus and influenza vaccines, referencing procedures outlined for public health emergencies such as pandemics.

Clarification of procedural guidance - The introduction and procedural guidance sections have been revised to clarify how EMA and National Competent Authorities manage Type IA, IB, II, and extension applications.

Updates to Quality changes in the annex - Amendments aim to improve alignment and consistency across scopes, sections, and product types. Key updates include:

• Incorporation of previous Article 5 recommendations and administrative/herbal product proposals.
• Removal of Roman numeral identifiers for C-scope changes and introduction of new codes.
• Downgrading of some Type II variations (e.g., design space extensions) to Type IB.
• Stricter conditions and documentation requirements for active substance changes.
• Updates to B.I.e and B.II.g categories to allow design space extensions as Type IB.
• New variation scopes to cover co-packaged, integral, and product-information-referenced medical devices, focusing on impact and risk.
• Streamlined language for safety, efficacy, and pharmacovigilance variations (Types IB and II).
• Clarified documentation for Plasma Master File (PMF) variations, including the downgrading of some changes.

Conclusion

The proposed updates to the Variations Regulation and Guidelines aim to streamline procedures and reduce administrative burden, resulting in a more efficient variation system. This should benefit both MAHs and regulatory authorities by accelerating processes and lowering workloads.

Early experience indicates that companies are already leveraging the new procedures, such as worksharing, super-grouping, and annual reporting, to improve efficiency. Ongoing monitoring will reveal the long-term impact of these changes.

What has your experience with the new guidance been? Have you noticed improved efficiency?

We invite you to share your comments. If you need assistance with interpreting the new guidelines or lifecycle management of your products, please contact us or visit G&L Scientific.

Mohit Sunkersett is a Senior Regulatory Manager at G&L Scientific.

References

(Draft) Guidelines on 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 (2013/C 223/01) EMA/269287.

Commission Regulation (EC) No. 1234/2008 Concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products.

Regulation (EC) No 2024/1701 Commission delegated 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 authorisations for medicinal products for human use.

Regulation (EU) 2019/4 on the manufacture, placing on the market and use of medicated feed, amending Regulation (EC) No 183/2005 of the European Parliament and of the Council and repealing Council Directive 90/167/EEC.

Regulation (EU) 2019/5 amending Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, Regulation (EC) No 1901/2006 on medicinal products for paediatric use and Directive 2001/83/EC on the Community code relating to medicinal products for human use.

Regulation (EU) 2019/6 on veterinary medicinal products and repealing directive 2001/82/EC

Regulation (EC) 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.