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Report and minutes from the CMDh meeting held on 12-14 November 2024
The reports from the CMDh meetings (also called press releases) reflect highlights/important outcomes of each meeting and are usually published in the week following the CMDh meeting. The reports therefore only contain a subsection of the complete CMDh agenda and are used for a more timely communication of the most important outcomes.
The CMDh minutes are a full record of the CMDh meetings (minus redaction of confidential content). They are adopted at the following CMDh meeting and subsequently published.
The report and minutes from the above meeting include (but are not restricted to) the following items:
1. CMDh Guidance on the Informal Work-Sharing procedure for follow-up for PSUSA for NAPs
The CMDh agreed an update of the CMDh Guidance on the Informal Work-Sharing procedure for follow-up for PSUSA for NAPs (PSUFU procedure).
- The guidance document has been updated to reflect the new approach for “other considerations” after the deletion of section 6 of the PSUSA AR.
- The updated document has now been published on the CMDh website under “Pharmacovigilance > PSUR > PSUSA Follow-Up”
- Here, you can view the track changed (Oct 2022) and clean (NOv 2024) versions of the document.
2. EMA/CMDh explanatory notes on variation application form
The CMDh agreed an update of the EMA/CMDh explanatory notes on the variation application form (human medicinal products only).
- Following the October revision, the document has been further updated to align the wording of the Variation Application Form and the amended Variation Regulation.
- The updated document Has now been published on the CMDh website under “Procedural Guidance > Variations > Amended Variation Regulation”.
- Here, you can view the track changed and clean (Nov 2024) versions of the document.
3. Guidance on the amended Variations Regulation
The CMDh discussed the questions from a MAH on the mandatory worksharing requirement set out in the amended Variations Regulation applicable as of 1 January 2025.
- PI update of a generic medicinal product where the MAH of the RefMP is not the same in all MSs
- The CMDh agreed that a PI update of a generic medicinal product where the MAH of the RefMP is not the same in all MSs could be included in a WS provided that the generic medicinal product can also refer to the harmonised product texts in the MS that does not have the current innovator text.
- However, no product-specific assessment should be necessary.
- Can safety updates of the originator can also be implemented for well-stablished use MAs in a worksharing without the requirement for type II C.I.4. variations to submit a full data package to substantiate the change
- The CMDh discussed the above.
- It was noted that from a regulatory perspective, the possibility of deviating from the requirements for type II C.I.4 variations for WEU MAs is not foreseen due to the lack of reference product.
- However, in some cases analogous to Q&A 3.23 of the CMDh Questions and Answers on Variations, a limited data package could be acceptable.
- The CMDh agreed that such proposals should be considered on a case-by-case basis.
- How to deal with the implementation of safety updates for more than one MA of the “same” product with different variation classification types applicable (due to different legal basis or different situations regarding the RefMP)
- The above was discussed.
- It was the CMDh view that a WS procedure should not apply to different variation categories/classifications and that, at least for the adaptation to the texts of the reference marketing authorization, i.e. C.I.2 variations, the (voluntary) upgrade to type II may allow the WS.
- The inclusion of WEU requests should also be pre-discussed and decided on a case-by-case basis.
- The CMDh will present the feedback to these questions during the CMDh meeting with Interested parties that will be held on 20 November 2024.
- The EC will also provide input in writing before the meeting.
4. Submission of parallel national variations instead of worksharing
The CMDh discussed a request for variation worksharing instead of parallel national variations.
- Due to the risk of disharmonisation across the EU, the CMDh agreed that the changes to update section 4.2 of the SmPC should be submitted via variation worksharing.
- The worksharing should include MAs in all MSs where the product is authorised, even if the variations are already in an advanced stage or have been finalised.
- It was noted that the CMDh already agreed in principle in 2022 to request the MAH to harmonise the product information via variation worksharing.
- However, eventually no letter was sent at the time.
- A letter will be sent to the MAH.
5. Implementation of contraindications with active substances not authorised in the EU and need for variation worksharing
The CMDh discussed a national type II variation submitted in Ireland for the implementation of a known contraindication with an active substance not authorised in the EU.
- Medicinal products containing this active substance were withdrawn from the EU market in the past for commercial reasons.
- A previous discussion was noted, where the addition of information on this interaction was not supported.
- Some MSs raised that clinical relevance on having this information in the EU/EEA product information and the extent to which concomitant use is to be expected is currently not clear.
- In a trend vote, the majority of CMDh was in favour of accepting the variation for assessment.
- There was also a general agreement that this update should be addressed via a variation worksharing procedure to ensure a harmonised outcome (although there were doubts concerning the feasibility of a WS including all MSs due to the different opinions) and that the MAH should provide additional justification to further support the inclusion of the contraindication and interaction warning in EU product information as part of this future WS procedure.
6. Variation submission strategy for changes to names/addresses of API manufacturers
The CMDh discussed a question from a MAH regarding the submission strategy of supergrouping variations that will impact a huge number of MAs in EU (more than 6000).
- In order to ensure smooth approval process and to prevent disruption of supply to patients the applicant proposed to split them in two groups by variation category, including not more than 30 procedures in one submission.
- The CMDh agreed with the applicant’s proposal.
- However, it would be preferable to reduce as much as possible the number of submissions and the NCAs where they will be submitted.
- It was noted that submissions could also be grouped by INN for the ASMF updates and purely national procedures could be included as from 1 January 2025 when the amended Variation Regulation becomes applicable.
- It was also noted that large submissions could cause technical problems for some MSs.
- The company will be informed accordingly.
7. Exchange of information on generics/hybrids between EMA and MSs
The EMA informed the CMDh of their intention to publish track change versions of the updated PI of centrally authorised Reference Medicinal Products or RefMPs (i.e. products for which there are centrally authorised generics) following the finalisation of variations of those products.
- The EMA will no longer actively inform centrally authorised generics of such PI updates but expects the generic MAHs to monitor the EMA website for updates and to implement the changes.
- As a consequence, this information will also no longer be shared with the CMDh.
- It was clarified that the MAHs will be requested to prepare “clean” track change versions of the PI for publication, based on guidance provided to them.
- The track change PI document will also include a statement to which variation the change refers.
8. Legal basis for product where proposed indications are not supported by RefMP for particular strengths
Ireland informed the CMDh about an application submitted under Art. 10(3).
- Different RefMPs for the product information (belonging to the same GMA) have been chosen per MSs that (partly) have different indications per strength.
- The applicant has applied for all indications for all strengths and chosen the legal basis Art. 10(3) due to a change in the therapeutic indications.
- Although it is the responsibility of the applicant to choose the legal basis, it was questioned if Art. 10(3) is applicable in this case as no new/additional data will be provided with the application to support the indications.
- The CMDh agreed that in the given situation an application under Art. 10(1) with all indications applied for all strengths can be accepted as the RefMPs belong to the same Global Marketing Authorisation (GMA).
- If an indication is not present for a certain strength in the RefMP, the applicant has to justify the inclusion of this indication for the strength(s) in the generic application.
- This will then be assessed during the procedure. For those strengths an application under Art. 10(3) without additional data but including a justification would also be acceptable.
- It was noted that according to the proposed posology, not all indications make sense for all strengths. This should be discussed with the applicant before the start of the procedure.
9. Bioequivalence studies for two strengths with different RefMPs belonging to different GMAs
The CMDh noted the EC feedback to a query raised in the May 2024 CMDh meeting (topic 4.4).
- The EC confirmed that there are no legal provisions in the legislation preventing bioequivalence studies conducted for two strengths within the same procedure with different RefMPs belonging to different GMAs (based on the provided rationale for conducting bioequivalence studies with different RefMPs in this case).
- It was noted that the indications applied for in the generic application have been aligned based on the SmPCs of the two RefMPs and strengths.
10. DCP application in parallel to centralised and decentralised procedures under the same GMA
The CMDh noted the EC feedback to the question if a new DCP is acceptable if the applicant owns MAs authorised in a CP and in a DCP, due to previous acquisitions (the applicant is the same as the MAH of the CAPs and the MAH of the MA resulting from DCPs are different but belong to same mother company or group of companies), raised in the June 2024 CMDh meeting (topic 3.12).
- The EC confirmed that according to Article 82(1) of Regulation (EC) 726/2004 in principle only one marketing authorisation may be granted to an applicant for a specific medicinal product.
- The Commission Communication 98/C 229/03 states that a product should not be authorised through different procedures.
- However, the purpose of the rules, especially the avoidance of a duplication of scientific evaluation with potentially different results, does not apply to generics to the same extent, given that their authorisation is based on a reference medicinal product and an existing assessment.
- As a consequence, an applicant may choose for a generic medicinal product between the central authorisation pathway and the national authorisation pathway and an applicant may replace a central generic marketing authorisation by a DCP generic marketing authorisation, provided that with the application a commitment is submitted to withdraw the central marketing authorisation, once the DCP authorisation is granted.
- It is therefore acceptable to submit a new DCP if the applicant already owns MAs in a CP and in a DCP under the condition that the applicant has given a commitment not to have marketing authorisations in both systems and if the product under development is classified as a generic.
11. Implementation of the amended Variation Regulation
The CMDh noted the EC feedback to questions raised in relation to the amended Variation Regulation, specifically in relation to annual reports and possible transition periods.
- It was clarified that Type IA variations that have been implemented in 2024 have to be submitted according to the current rules i.e. as a single submission or grouping within 12 months of its implementation.
- Type IA variations implemented on or after 1 January 2025 should follow the amended Variation Regulation (Regulation (EU) 2024/1701 of 11 March 2024) and are expected to be submitted as an annual update, unless one of the exemptions is applicable and used by the MAH.
- It was further clarified that the amended Variation Regulation entered into force in July 2024 which gave about 6 months for preparation for the implementation.
- Companies were also closely involved in the preparation and consultation procedures before the adoption of the Regulation. Therefore, a transitional period for implementation of the procedures is not expected.
Source: CMDh
Minutes and presentation from the 14 November 2024 meeting of a subgroup of CMDh with Interested Parties
You can view the minutes of the above meeting here and the presentation from the meeting titled Safety Variation Example can be viewed here.
Source: CMDh