Last updated: 6 February 2023
See updates at the end of the post.
Report and minutes from the CMDh meeting held on 13-14 December 2022
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 limited to) the following items:
1) Removal of requirement to provide list of dispatch dates
The CMDh has agreed updates of several CMDh guidance documents to remove the requirement for MAHs to provide a list of dispatch dates (dates of dispatch to the CMS) with the RMS submission. With the mandatory use of CESP for submissions, it was considered that the list of dispatch dates is no longer needed. The review follows an update of the CMDh BPG for the handling of Type II Variations in MRP (Chapter 5) in October, where this change was first agreed. The following CMDh guidance documents have been updated:
- Chapter 2 – Procedure for automatic validation of MRP for Variations. Here, you can view the track changed and clean (Dec 2022) versions of the document
- Chapter 3 – CMDh BPG for the processing of Type IA Minor Variations (Notifications) in MRP. Here you can view the track changed (Dec 2022) and clean (Dec 2022) versions of the document.
- Chapter 4 – CMDh BPG for the processing of Type IB Minor Variations (Notifications) in MRP. Here you can view the track changed (Dec 2020) and clean (Dec 2022) versions of the document.
- Chapter 5 – CMDh BPG for the handling of Type II Variations in the Mutual Recognition Procedure. Here you can view the track changed (October 2022) and clean versions of the document. The changes are in section 4 Submission Phase, 8 Outcome and Annex II
- Chapter 6 – CMDh BPG for the processing of Grouped Applications in MRP. Here you can view the track changed (July 2021) and clean (Dec 2022) versions of the document.
- Chapter 7 – CMDh BPG on Worksharing. Here you can view the track changed (July 2022) and clean (Dec 2022) versions of the document.
- Cover letter for Variation Applications in the MRP. Here you can download the version of December 2022.
- CMDh Best Practice Guide on the processing of renewals in the MRP/DCP. Here you can view the track changed (Nov 2020) and clean (Dec 2022) versions of the document.
Other minor changes have been included in the updated documents, as necessary. Chapter 5 has also been further updated to be in line with the other CMDh BPGs. Here, you can view the track changed (Oct 2022) and clean (Dec 2022) versions of the document.
The updated documents have now been published on the CMDh website under “Procedural Guidance > Variations”, “Templates > Variations” and “Procedural Guidance > Renewal”, respectively.
2) Call for review for chemically synthesised and biological medicinal products regarding nitrosamine impurities
The CMDh and the EMA agreed an update of the EMA/CMDh Q&A on nitrosamines. The Q&As have been updated to provide guidance on the approach to control the presence of nitrosamines exceeding the acceptable intake (AI) during CAPA implementation. In addition, further clarification is provided on the application of the temporary universal AI of 178 ng/day.
The updated document has been published on the EMA website and will be linked from the CMDh website under “Advice from CMDh > Nitrosamine impurities”. You can view the updated document dated 21 December 2022 here. The following updates have been made to the document:
- Update of Q&A 20 to consider the possibility of an interim limit based on the LTL approach during CAPA implementation.
- Update of Q&A 21 for increased clarity on the application of the temporary universal limit.
- Introduction of Q&A 22 on approach to control presence of Nitrosamine exceeding the AI while CAPAs are being implemented.
3) CMDh position paper concerning Applicant’s request of submission of multiple applications during ongoing DCPs or inclusion of new CMS or additional strength(s) in an already ongoing DCP
The CMDh agreed an update of the CMDh position paper concerning applicant’s request of:
- submission of multiple applications during ongoing DCPs or
- inclusion of new CMS or additional strength(s) in an already ongoing DCP.
With the update, the CMDh provides conditions for the inclusion of new CMS during an ongoing DCP (in case of no on-going multiple/duplicate application with the same CMS), specifically to prevent or solve shortages.
There was a discussion how on much information the applicant has to provide to justify the addition of the new CMS due to prevention or solving of a shortage.
- It was agreed by majority that the guidance will only request a justification.
- It was noted that it will be the decision of the CMS to accept the inclusion during an ongoing procedure.
- The CMS can always request additional data/justification, as needed.
- It was further agreed not to include timelines in the guidance document for the decision of the new CMS to be included in the procedure.
- In case of shortages a quick decision is expected.
The updated document has now be published on the CMDh website under “Procedural Guidance > Application for MA”. Here, you can view the track changed (Oct 2017) and clean (Dec 2022) versions of the document.
4) Update of Applicant’s (Joint) Response Template
The CMDh agreed an update of the applicant’s (joint) response template – responses to the question raised by RMS and CMSs. A new section has been added for the applicant to provide information (and to keep the RMS informed) about the changes proposed by the applicant in the manufacturing chain and/or in the submitted GMP documents, including the submission of more recent versions during the further steps of the procedure. The use of the template will become mandatory as of 1 February 2023 for all upcoming responses but can already be used on a voluntary basis before that date.
The updated template has now been published on the CMDh website under “Templates > Assessment reports DCP (AR/Comments)”. You can download it here.
5) Q&As on Active Substance Master File (ASMF)
In June 2022, the CMDh adopted an update of the Q&As on ASMF. The update gives further guidance on the version numbering of ASMFs, how to track them and how they relate to the eCTD sequence.
The Q&As are a joint document with several other groups and all involved parties have now adopted the update. The updated document (Rev. 12 of November 2022) has therefore been published on the CMDh website under “Questions and Answers”. Here, you can view the track changed and clean versions of the document. There are updates to the Q&As for the following questions:
- 22. Where an ASMF Holder prepares a new version of ASMF following finalisation of a marketing authorisation or variation application, can the MAH inform Authorities about this new version by submitting an official letter? (updated, November 2022)
- 23 Since all changes in new ASMF version have already been communicated to the authorities during a marketing authorisation application or variation application, can the MAH submit the updated sections of a new version in eCTD format outside of scope of variation? (updated, November 2022)
- 26. How should different version numbers be tracked? (new, from previous Q25, November 2022)
- 27. How is the version numbering of ASMF’s related to the eCTD sequence? (new, November 2022)
6) Water for injection included in MAs of medicinal products
In September and October, the CMDh discussed and agreed that cross-reference to a standalone marketing authorisation is not permittable in the dossiers of medicinal products. Each authorised medicinal product must contain all the particulars and requirements as laid down in the legislation, including all information on the quality aspects. This was communicated to a MAH that had taken the approach in agreement with the RMS to remove most of the quality information of a solvent from the dossiers and to include instead a cross-reference to the stand-alone MA for the solvent (water for injection). The MAH was asked to re-introduce the information in their dossier.
The CMDh was of the opinion that the regulatory framework is clear. Article 8(3) and Annex I of Directive 2001/83/EC clearly specify the particulars and documents to be submitted with a MAA. Cross-reference to the quality information of a different MA is not foreseen. The fact that such reference is not mentioned in legislation does not automatically mean that it is allowed. The CMDh considered that there is no need to further discuss the issue. A response will be sent to the MAH
7) Submission of MAA via DCP (for a different indication) for existing CAP (same medicinal product)
The CMDh discussed if a MAH of a product authorised via the centralised procedure could apply for the same product via the DCP for a different indication, provided that that indication does not fall within the mandatory scope of the centralised procedure.
The RMS recognised the general principle that both an EU and a national marketing authorisation are not allowed to coexist simultaneously for the same product according to
Commission Communication 98/C 229/03.
However, as already previously confirmed by the EC in the past, in addition to the general principle from the Commission Communication 98/C 229/03, a possible co-existence of central and national marketing authorisations for different therapeutic indications was also addressed in the Communication: “In order to maintain coherence and transparency, and to preserve the unity of the Community Single Market, where the same marketing authorisation holder wishes to place on the market another medicinal product with the active substance which is already the subject of a Community authorisation, the Commission considers that the centralised procedure should be used, in particular when the therapeutic indication is within the third level of the ATC code.”
In this case the indications diverge at the second level of the ATC code. Therefore, the RMS was of the opinion that the DCP application could be allowed. The CMDh agreed with the RMS position. The European Commission disagreed with this position in this case as follows:
Post-meeting, The CMDh received feedback from the EC, who considered that the approach would not be appropriate, in this specific case, to have a second MA application assessed in the DCP in parallel of an already granted authorisation granted by the European Commission. This is in line with the general principle contained in the Commission Communication 98/C 229/03 (point A.2) that there cannot be co-existence between a central and a national authorisation for the same medicinal product, with the need to ensure consistency of the risk assessment, and finally to avoid a circumvention of the legal requirements for duplicate marketing authorisation applications.]
Decisions on an additional year of market protection/data exclusivity for new therapeutic indication agreed by the CMDh
Revision 2 of the above document dated December 2022 has now been published and is available here.
Update(s)
| Date | Update(s) |
|---|---|
| 6 Feb 2023 | 1) Heading Report from the CMDh meeting held on 13-14 December 2022 updated to Report and minutes from the CMDh meeting held on 13-14 December 2022 and a link to the minutes from the meeting has been added. 2) Point number 1 under the above heading has been updated to add a link to the track changed and clean versions of Chapter 5 of the BPG. 3) Point number 3 under the above heading was updated to add the paragraph commencing ‘There was a discussion on how much information….etc’ 4) Points no 6 and 7 were added, with relevant content. |
| 5 Jan 2023 | Links added to updated documents mentioned in points no 1, 3 and 4 under the heading Report from the CMDh meeting held on 13-14 December 2022 |