Last updated: 26 November 2024
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This post provides information on the ongoing changes to the EU the variation Regulation (EC) No 1234/2008 and guideline.
Timeline of events leading to the publishing of the commission delegated regulation
| Date | Event |
|---|---|
| Call for evidence Feedback period 29 August 2023 – 26 September 2023 | This initiative, announced in the 2020 pharmaceutical strategy for Europe, aims to review the current rules setting out the procedures for post-authorisation changes to a marketing authorisation for medicines for human use. The purpose is to make the lifecycle management of medicines more efficient. Further information on this page. |
| Draft act Feedback period 07 February 2024 – 29 February 2024 | Further information on this page. |
| 11 March 2024 | The Commission adopted the Delegated regulation. Further information on this page. |
| 13 June – 23 August 2024 | Stakeholder consultation on the proposed amendments to the European Commission guidelines on variations categories and procedures. Further information provided below after the table. |
| 17 June 2024 | The amendments to the Variation Regulation (i.e. new measures for the better lifecycle management of medicine authorisations) were published in the Official Journal of the European Union. You can view them at the link below. 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 products for human use This Regulation entered into force on the twentieth day (7 July 2024) following that of its publication in the Official Journal of the European Union. It shall apply from 1 January 2025. This Regulation shall be binding in its entirety and directly applicable in all Member States. |
Stakeholder consultation on the proposed amendments to the European Commission guidelines on variations categories and procedures
As part of the 2020 Pharmaceutical Strategy for Europe, the Commission is reviewing the current rules governing the procedures for post-authorisation changes to the terms of a marketing authorisation for medicines products for human use, with the purpose to make the lifecycle management of medicines more efficient and future proof and ensuring the protection of public health in the European Union.
- In this context, the Commission proposed a draft delegated Regulation amending Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and its annexes (Variations Regulation) within the existing legal framework of Regulation (EC) No 726/2004 and Directive 2001/83/EC.
- The draft delegated regulation was adopted on 11 March 2024 and Commission Delegated Regulation (EU) 2024/1701 was published in the OJEU on 17 June 2024.
- As a next step, the Commission is reviewing the Guidelines on the details of the various categories of variations and operation of the procedures (Variations Guidelines) and, in this respect, proposed amendments compatible with the current legal context are hereby released for the stakeholders consultation with a commenting period until 23 August 2024.
What are the main changes being proposed to the variations guideline?
Overall, the main changes proposed to the Introduction and Procedural section of the Variations Guidelines include:
- the addition of procedural details on the new/revised regulatory tools introduced with the proposed Variations Regulation (e.g. on super grouping of Type IA variations,
- annual update of Type IA variations,
- mandatory use of worksharing procedure and
- extension of update flexibility to human vaccines addressing a public health emergency in the Union.
Other changes being proposed to the variations guideline
Other changes include:
- The introduction and procedural guidance sections have been further simplified and updated to reflect the current practice of EMA and National Competent Authorities.
- The Annex to the Variations Guidelines, including the different categories, conditions and documents to be submitted has also been reviewed taking into consideration the experience acquired and the scientific and technical progress.
- Previous Article 5 recommendations for unforeseen variations have been integrated into the current proposal, as appropriate, and targeted proposals have been made on the administrative variations.
- The current code system for variations has been maintained, with the deletion of the Roman numeral“I” (relating to variations for human medicines) on the C-scopes and a sequential numbering implemented.
Documents provided in support of the consultation
The following documents are provided:
- Executive summary for proposed amendments to the European Commission guidelines on variations categories and procedures which can be viewed here.
- Track changed and clean versions of the document European Commission guidelines on variations categories and procedures: Proposal for stakeholder consultation
What were the consultation start and end dates?
Consultation start date: 13 June 2024
Consultation end date: 23 August 2024
The consultation is now closed.
What are the next steps?
The European Commission is currently reviewing the guidelines on the details of the various categories of variations and operation of the procedures and an updated version is expected during 2025.
Source: EMA
Guidance on the implementation of the amended Variations Regulation (EU) 2024/1701 for variation applications implemented and submitted 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 (see below).
What will happen during the transition period from 1 January 2025 until the date when the updated Variations Guidelines become applicable?
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 on the CMDh website. Links to the various guidance documents are also provided below.
Are there any changes to variations submitted before 1 January 2025?
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.
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) 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 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- MRP variations
Best Practice Guides (BPGs) for the Submission and Processing of Variations in the Mutual Recognition Procedure
| Chapter | Title of guidance | Track changed and clean versions of the guidance |
|---|---|---|
| Chapter 1 | CMDh BPG for the Allocation of the Mutual Recognition Variation Number for Type I Notifications, Type II Variations, Grouping and Worksharing | track changed (Jan 2020) and clean (Oct 2024) versions |
| Chapter 2 | Procedure for Automatic Validation of Mutual Recognition Procedures for Variations | track changed (Dec 2022) and clean (Oct 2024) versions |
| Chapter 3 | CMDh BPG for the Processing of Type IA Minor Variations (Notifications) in the Mutual Recognition Procedure | track changed (Dec 2022 ) and clean (Oct 2024) versions |
| Chapter 4 | CMDh BPG for the Processing of Type IB Minor Variations (Notifications) in the Mutual Recognition Procedure | track changed (Jul 2023 ) and clean (Oct 2024) versions |
| Chapter 5 | CMDh BPG for the Handling of Type II Variations in the Mutual Recognition Procedure | track changed (Jul 2023 ) and clean (Oct 2024) versions |
| Chapter 6 | CMDh BPG for the Processing of (Super-)Grouped Applications in the Mutual Recognition Procedure | track changed (Dec 2023 ) and clean (Oct 2024) versions |
| Chapter 7 | CMDh BPG on Variation Worksharing | track changed (Dec 2023 ) and clean (Oct 2024)versions |
| Chapter 8 | CMDh BPG on CMDh Recommendations on Unforeseen Variations | track changed (Feb 2022) and clean (Oct 2024) versions |
Other Documents
| Document | Track changed and clean versions of the document |
|---|---|
| EMA/CMDh Explanatory notes on variation application form (Human medicinal products only) | Track changed (July 2022) and clean (Nov 2024) versions |
| Examples for acceptable and not acceptable groupings for MRP/DCP products | Track changed (May 2022) and clean (Oct 2024) versions |
| Position paper common grounds seen for invalidation/delaying day 0 for variations | track changed (Feb 2023) and clean (Oct 2024) versions |
| Q&A – List for the submission of variations for human medicinal products according to Commission Regulation (EC) 1234/2008 | Track changed (May 2024) and clean (Oct 2024) versions |
| Template Cover letter for the submission of variation applications in the MRP | Track changed (Dec 2022) and clean (Oct 2024) versions |
| 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 | Track changed (July 2013) and clean (Oct 2024) versions |
| Template request for a recommendation on the classification of an unforeseen variation under Article 5 of Commission Regulation (EC) No 1234/2008 | Track changed and clean (Oct 2024) versions |
| Urgent Safety Restriction Member State Standard Operating Procedure | Track changed (Feb 2017) and clean (Oct 2024) versions |
Source: CMDh
Guidance applicable from 1 January 2025- Centralised procedure variations
| Document | Track changed version of the document |
|---|---|
| European Medicines Agency post-authorisation procedural advice for users of the centralised procedure – Type IA Variations | Track changed |
| European Medicines Agency post-authorisation procedural advice for users of the centralised procedure – Grouping of variations | Track changed |
| European Medicines Agency post-authorisation procedural advice for users of the centralised procedure – Worksharing of variations | Track changed |
| EMA Procedural Advice on Recommendations on unforeseen variations according to Article 5 of Commission Regulation (EC) No 1234/2008 | Track changed |
| Template : Letter of intent for the submission of a worksharing procedure to the European Medicines Agency | Track changed and clean versions |
Source: EMA