Last updated 26 April 2023
See updates at the end of the post.
European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure
This document has been updated. Here you can view track changed (Dec 2022) and clean (Apr 2023) versions of the document.
It seems that the only change to the documents is in the response to Q4.1 How and to whom should I submit my dossier?
Source: EMA
Report and minutes from the CMDh meeting held on 28-30 March 2023
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 Best Practice Guide (BPG) on fast-track procedure for the annual update of human influenza vaccines
The CMDh agreed an update of the BPG on fast-track procedure for the annual update of human influenza vaccines.
- The guidance was updated, among others, to remove the requirement for the applicant to provide a list of dispatch dates, in line with the update of other CMDh guidance documents.
- Annex III has been aligned with the labelling requirements of Annex II to Guideline on influenza vaccines – submission and procedural requirements (EMA/56793/2014) as agreed by the CHMP BWP ad hoc Influenza Working Group.
The updated document has been published on the CMDh website under “Procedural Guidance > Variation”. A link will be provided here. Here, you can view the track changed (Mar 2017) and clean (Mar 2023) versions of the document.
2. Call for review for chemically synthesised and biological medicinal products regarding nitrosamine impurities
The CMDh in collaboration with the EMA agreed an update of the joint EMA/CMDh Questions and Answers for MAHs/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products.
- Q&A 22 What is the approach to control presence of N-nitrosamine exceeding the AI during CAPA implementation? has been amended to indicate that no variation should be submitted to implement temporary above AI limits in specifications.
- The updated Q&A document (Rev. 14 March 2023) has been published on the EMA website. A link is provided from the CMDh website under “Nitrosamine impurities”. You can view the document here.
3. Update of CMDh guidance documents related to renewals
Following the update of the CMDh BPG on the processing of renewals in MRP and DCP in February with a new simplified standard process, the CMDh has now also agreed updates of the following guidance documents that are either related to renewals or where renewal procedures are mentioned, to reflect the new process:
- CMDh procedural advice on common grounds seen for delaying D0 renewals. There are substantial changes throughout the document. Here you can view the track changed (July 2017) and clean (Mar 2023) versions of the document.
- Member State agreement upon conditions under which the RMS can start renewals. There are changes in all sections of the document except Section 1 Legal background. Here you can view the track changed (July 2017) and clean (Mar 2023) versions of the document.
- Recommendations on informed consent applications in MRP and DCP. The only section which appears to have changes is Section 6 Maintenance of the dossier following granting of the informed consent marketing authorisation. Here you can view the track changed (July 2022) and clean (Mar 2023) versions of the document.
- Template for request for MRP/RUP – A minor additional change has been included. YOu can download the updated template here.
- Template for end of renewal procedure – You can download the updated template here
- Questions & Answers on renewals – New Q&As have been included to provide guidance on the new process. Here, you can view the track changed and clean (March 2023) versions of the document.
The updated documents have all been published on the CMDh website and links have been provided above.
4. Regulation (EC) No 1234/2008 on variations
The CMDh has discussed a recommendation for the classification of an unforeseen variation submitted to the EMA for a centrally authorised product.
- The CMDh agreed with the EMA that the proposed change (“Change in the specification parameters and/or limits of the active substance, starting material, intermediate or reagent used in the manufacturing process of the active substance to more accurately describe the appearance of active substance, starting material, intermediate or reagent”) can be submitted as a type IA variation under B.I.b.1.z (certain conditions apply and all have to be met).
- The outcome has been included in the CMDh list of Art. 5 recommendations and published on the CMDh website under “Procedural Guidance > Variation > Article 5 recommendations”. You can download it here.
5. Submission of parallel national variations instead of worksharing
Example 1
- Following a request to a MAH of nationally authorised medicinal products to submit an update of SmPC section 4.1 and 4.2 and relevant sections of the PL to include a new indication via variation worksharing, the CMDh noted the response of the MAH.
- The MAH requested to proceed with the national variations due to the advanced stage of the submissions in some MSs.
- The CMDh remained of the opinion that the variations should be submitted via the worksharing procedure in those MSs where the MAH has applied for the new indication and in those where the indication is already approved, in order to achieve a harmonised outcome and to avoid duplication of work. A corresponding letter will be sent
Example 2
- The CMDh was informed of the submission of parallel national variation instead of a
- worksharing. The MAH is applying for an update of SmPC sections 4.4, 4.8 and 5.1 based on an update of the company core data sheet.
- The MAH informed the NCAs that national variations have been chosen instead of worksharing as the changes are not identical in all MSs and some amendments are wording-specific.
- The CMDh considered that worksharing can be used in this case as all changes have the same clinical background and should be included in a harmonised way in the national MAs independent from the currently not harmonised national texts.
- The CMDh agreed to request the MAH to submit the changes as variation worksharing procedure (Action: EMA).
- Additional editorial changes that were submitted only for single MS can be submitted in the national phase after the worksharing.
6. General topics on nitrosamines
- The CMDh agreed that the nitrosamine subpage on the CMDh website will be moved to a more prominent level on the website. MSs will be informed in case the direct link changes due to the amendment.
- The CMDh in collaboration with the EMA agreed an update of the joint EMA/CMDh Questions and Answers for MAHs/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products. Q&A 22 has been amended to indicate that no variation should be submitted to implement temporary above AI limits in specifications.
- The updated Q&A document will be published on the EMA website.
- You can view the updated document here.
7. Definition of “Applicant” in MRP/DCP applications
Based on a statement in the CMDh User Guide for the electronic Application Form for a
Marketing Authorisation that for MRP and DCP applications, the CMDh discussed if the
applicant should be the same as the MAH/Applicant in the RMS. Due to different
interpretations by MSs it was clarified that:
- For DCP applications, the Applicant in all Member States should be the same but can differ from the future MAH (and the future MAH can also be different per Member State).
- For MRP applications, the Applicant in all Member States should be the MAH in the RMS, but the future MAH can differ.
Updates
| Date | Update(s) |
|---|---|
| 26 Apr 2023 | 1) Heading Report from the CMDh meeting held on 28-30 March 2023 as updated to Report and minutes from the CMDh meeting held on 28-30 March 2023 and a link added to the minutes from the meeting. 2) Under the heading Report and minutes from the CMDh meeting held on 28-30 March 2023, items 5, 6 and 7 were added. |
| 25 Apr 2023 | Added link to the updated document European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure. |
| 20 Apr 2023 | Links added to the the following documents listed in section 3. Update of CMDh guidance documents related to renewals: · UPDATE – Recommendations on Informed Consent Applications in Mutual Recognition and Decentralised Procedures · UPDATE – Common grounds seen for delaying Day 0 Renewals · UPDATE – Member State agreement upon conditions under which the RMS can start renewal procedures · UPDATE – Request for MRP/RUP / Update assessment report |
| 19 Apr 2023 | Link added to the updated Renewals Q&A in the section 3. Update of CMDh guidance documents related to renewals |