CMDh and other EU updates – March 2024

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Last updated: 7 June 2024

See updates at the end of the post.

Report and minutes from the CMDh meeting held on 19 – 20 March 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. Procedural advice on Zero Day MR Procedures

The CMDh agreed on a new procedural advice on Zero Day MR Procedures.

  • The Zero Day Procedure is a mutual recognition procedure with a shortened timetable, which can be initiated in exceptional cases to mitigate shortages or issues with access to critical medicines with agreement of the member states concerned.
  • The procedural advice document provides information on considerations prior to the initiation of the procedure, dossier requirements and the steps of the procedure.
  • The document has been published on the CMDh website under “Procedural Guidance > Application for MA > MRP/RUP”. You can view the document here.

2. Pharmacovigilance Legislation

The CMDh agreed an update of the CMDh Questions and Answers on Pharmacovigilance Legislation.

  • The Q&A 2 (“How should I submit a new RMP or an updated RMP to update my dossier?”) has been revised to stress that, for RMP updates, a clean and a tracked version (as a working document in word format) should be submitted to facilitate the assessment.
  • The updated Q&A document has been published on the CMDh website under “Questions & Answers”. You can view it here.

3. Pilot on reduced assessment of Art. 45 studies

The CMDh was updated about the ongoing project to optimise the assessment procedure for Art. 45 paediatric studies.

  • MSs were requested to reflect on the strategy to prioritise candidate APIs for the pilot and to volunteer as rapporteurs.
  • The Nethlerands volunteered as rapporteur for levothyroxine/liothyronine, liothyronine, rifabutin and somatropin.
  • The relevant MAHs will be requested to submit data to be considered for a reduced assessment procedure, using the agreed pilot letter and table template to standardise the submission of information.

4. TiO2 (E171) used as excipient

The final feedback from EMA to the EU Commission request to evaluate the feasibility of alternatives to replace titanium dioxide (TiO2) in medicinal products and its possible impact on medicines’ availability was presented to the CMDh.

The document was adopted by the CMDh and will be sent to the EC after the meeting.

Update on new fee regulation (highlight from the EMA management board meeting, March 2024)

The Board noted that work on preparation for the implementation of the new fee regulation has begun.

  • This includes the redrafting and updating of various documentation including the cooperation agreement with national competent authorities (NCAs) and the working arrangements that will replace the current implementing rules.
  • The working arrangements will further clarify the terminology and requirements of the new regulation, outline conditions for fee incentives and provide a description of payment modalities including remuneration to NCAs.
  • From 1 January 2025, the new fee regulation will be implemented across the EU. It aims to:
    • provide harmonisation between the fee regulation and pharmacovigilance fee regulation,
    • align fees with underlying costs and
    • reduce the current complexity of the fee system

Source: EMA

eCTD v4.0 EU M1 Implementation Guide – draft Version 1.1 now available

A new draft version of the eCTD v4.0 EU M1 Implementation Guide is now available here for consultation. Future versions (together with EU Controlled Vocabularies and other annexes) will be published and announced on the eSubmission website.

Source: eSubmissions

CTCG Best Practice Guide for sponsors of multinational clinical trials with different Part I document versions approved in different Member States under the Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014

Version 4 of the above was adopted at the CTCG plenary March 7 2024. You can view it here.

The changes in Version 4 are as follows:

  • Sponsor should propose trial category but not apply for low-intervention clinical at time of transition from CTD to CTR.
  • Details on CTIS submission for specific situations: i) sponsor is not product owner of an IMP, ii) recommendations for IMPs and AxMPs, iii) when, under CTD, a study was regarded as an interventional clinical trial in some Member States and as a non-interventional clinical study in other Member States.
  • Archiving rules and end of trial for CTD trials when some but not all Member States included in transition.
Annex Cover Letter Template vs. 4.0 adopted at CTCG plenary March 6 2024

You can view the Cover letter template here.

Report and minutes from the CMDh meeting hold on 20-22 February 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 Best Practice Guide (BPG) on Multilingual packaging

The CMDh agreed an update of the BPG on Multilingual packaging.

The main changes to the updated BPG document are:

  • the addition of instruction for the preparation of an ‘EU full/reduced harmonised labelling text’ in the RUP and line extension procedures,
  • guidance on changing MS clusters where the “EU reduced harmonised text” is already approved or to change an already approved “EU reduced harmonised text”,
  • update of the section on Product names and reformatting of Annex I and II.

The updated document has been published on the CMDh website under “Procedural Guidance > Application for MA”. Here, you can view the track changed (Oct 2021) and clean (Feb 2024) versions of the document.

2. DCP Quality Assessment Report template

The CMDh agreed an update of the DCP Quality AR template. The document has been updated to delete the administrative information table as it was considered to be a duplication of the information already included in the Overview AR template.

The updated document will be published on the CMDh website under “Templates > Assessment Reports > DCP (AR/Comments)”. You can view the updated template here.

3. Meeting of a subgroup of CMDh with Interested Parties dedicated to LoSC and publication of PI updates

The subgroup of the CMDh (including the Safety Outcome Survey (SOS) Working Group) convened a dedicated meeting with representatives of Interested Parties on 22 February 2024.

In the meeting a status update on the new upload system for List of Safety Concerns (LoSC) via web interface was given and the SOS WG initiative on publication of the outcomes of safety variations was discussed.

All presentations have been published on the CMDh website under “About CMDh > Contact with Representative Organisations”. You can view them at the links below:

4. Variation worksharing procedures including non-prescription and prescription-only products

Based on a recent example, the CMDh discussed how the agreed OTC wording can be included in section 15 (instructions on use) of the common label wording, when both nonprescription and prescription-only products are included in a variation (worksharing).

Two possible approaches were presented:

  • State both OTC and prescription-only options in the common label wording in section 15 of the label of medicinal products with different legal status, with the understanding that only OTC products use this wording in the national label and that this section of the national label would be left blank for a POM.
  • Leave the common label wording in section 15 of the label of medicinal products with different legal status blank and OTC instructions would be fully handled in the national phase.

There was no majority in the CMDh for either of the options. The CMDh agreed to refer the question to the OTC Task Force.

5. Guideline on the environmental risk assessment of medicinal products for human use / EMA

The CMDh was informed about the revision of the Guideline on the environmental risk assessment of medicinal products for human use. The revision was adopted by CHMP in February 2024. Publication is planned for early March. The implementation date is 1 September 2024. Assessors training and interested party engagement is planned in advance of the implementation.

  • It was highlighted to CMDh that the wording of the current PAR template should be updated to be in line with the guideline.
  • The CMDh stressed the need for further guidance and that the CMDh needs to be involved in the preparation of the implementation.
  • As the time until the implementation is limited, it was proposed to have a meeting in March between EMA and CMDh representatives to further discuss a harmonised implementation.

6. MAA Electronic Application Form

Following discussion in the eAF maintenance group, the CMDh discussed if section 2.4.1. of the eAF for new MAAs should be updated to include either a drop-down menu or a free text field to give the possibility to add national specifics regarding the MAH (e.g. local representative and co-distributor).

  • The discussion was triggered as in some MSs the MA can only be granted based on the information in the eAF. If certain national information is not available in the eAF, the MAH has to submit a variation to add the information after the MA has been granted.
  • MSs expressed different positions. Some mentioned that e.g. the local representative is provided in other sections of the eAF or in the cover letter. It was also noted that this would open the door to requests of a lot of country-specific, additional information via the eAF.
  • The CMDh agreed by majority that such national requirements/information should not be included in the eAF.
  • On a different issue, the eAF maintenance group was asked to harmonise the information given in the eAF with regard to ASMF and CEP holders (company name vs name and address)

7. Request for variation worksharing procedure including several safety updates

The CMDh discussed a request from a MAH for a complex variation worksharing procedure including several grouped safety updates. The CMDh discussed if the procedure could/should be split into smaller packages.

  • It was noted that a general decision on a split cannot be made. A split would depend on the scope of the individual changes and whether all proposed changes are related to each other.
  • Generally, the MAH should provide a justification for the proposed grouping. It was also generally considered useful to review all changes together, but this would not be a valid reason to group unrelated changes.
  • As it concerns the implementation of safety information, the submission of individual changes should not be delayed.
  • In case more than one WS variation would be needed, these could be submitted and assessed in parallel at the same time with the same timetable.
  • The CMDh generally promotes the use of variation worksharing.
  • The reference authority could discuss with the MAH if some minor unrelated changes could be taken out of the procedure.
  • Due to the complexity of the procedure the reference authority was advised to use the longer timetable of 120 days.
EMA Eudravigilance Registration manual and documents

Revision 14 (13 March 2024) of the EMA EudraVigilance Registration Manual has been published. You can view it here.

Source: EMA

The Document EudraVigilance registration documents of 13 March 2024 has been published. You can view it here.

Source: EMA

Commission proposes new measures for the better lifecycle management of medicine authorisations – updated on 16 May 2024

The Commission has proposed to amend the variation legislation for medicines, to make the lifecycle management of medicines more efficient and better adapted to the modern context.

The Regulation, which is part of the EU’s Pharmaceutical Strategy for Europe, adapts the current system for variations to marketing authorisations, to make it more efficient, reduce administrative burdens and better respond to scientific and technological advances.

Since it was last revised, the Variations Regulation has made a marked contribution in harmonising and aligning the life-cycle management of medicines, post-authorisation, across the EU. However, the rules need to be updated in line with recent scientific and technological advancements and a rise in the number of variation requests.

The proposed revisions will facilitate quicker processing of variations, benefiting both marketing authorisation holders and regulatory authorities. They will facilitate more efficient lifecycle management of medicines while awaiting the broader proposed reform of the EU’s pharmaceutical legislation.

Update on 16 May 2024 – The Commission adopted the Delegated Regulation on 11 March 2024. Further information including links to the delegated regulation and its annex are available on this page.

You can read more about the changes here.

Source: European Commission; European Commission; Bioslice blog

Useful factsheets

The European Commission has recently published the following useful factsheets:

CMDh annotated QRD template for MR/DC procedures (Based on version 10.4 of the QRD template for CP)

This template has been updated. Here, you can view the track changed (April 2021) and clean (March 2024) versions of the document.

There are small changers throughout the document.

Source: CMDh

EudraVigilance – EVWEB User Manual

The Manual has been updated to version 1.7 (29 February 2024).

Revision 1.7 contains the following updates:

  • Figures 5 and 126 were amended.
  • Some hyperlinks were updated (in sections 1-4); − References to the ICH E2B(R2) message format were updated (or removed where applicable, as this message format was superseded by the ICH E2B(R3) format);
  • The following section was updated: 3.9.1 “Import Function”;
  • The following sections were added: 3.9.1.1 “Import of a single XML file”, 3.9.1.2 “Import of multiple XML files” and 3.11.3.2 “Use of Automation tools (API/RPA) in the ICSR download and Captcha control for Level 2B (L2B) download requests”;
  • Some editorial amendments were made to align the format with other EMA documents.

Source: EMA

Deadlines for submission of applications for orphan medicinal product designation to the EMA and corresponding COMP timetable for valid applications 2024/2025

You can view the submission deadline table here.

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

The document with the above title was updated in March 2024. Changes were made to the following Q&As:

  • 1.3. Is the (Co-) Rapporteur involved in the review of Type IA/IAIN variations? Rev. Mar 2024
  • 3.11. How shall my Type II application be handled (timetable)? Rev. Mar 2024
  • 3.25. When will I get a PIP compliance statement? Rev. Mar 2024
  • 3.27. Who is my contact at the European Medicines Agency during a type II variation, including extension of indications? Rev. Mar 2024
  • Whom should I contact if I have a pre-submission question when preparing my type II variation application? Rev. Mar 2024
  • 4.12. How shall my Extension Application be handled (timetable)? Rev. Mar 2024
  • 13.2. Under which procedure should I submit my non-interventional imposed PASS? Rev. Mar 2024
  • 19.1. What is a Transfer of Marketing Authorisation? Rev. Mar 2024
  • 19.2. How shall I present my application for the Transfer of Marketing Authorisation? Rev. Mar 2024
  • 19.5. How to choose the implementation date? Rev. Mar 2024
  • 19.8. How to handle remaining Post-authorisation measures and recommendations when transferring a Marketing Authorisation? Rev. Mar 2024
  • 19.13. Can I change the name of a medicinal product as part of a transfer application? Rev. Mar 2024
  • 19.14. Will there be any publication on the Transfer of Marketing Authorisation? Rev. Mar 2024
  • 19.15. Who should I contact if I have a question when preparing my application or during the procedure? Rev. Mar 2024

Source: EMA

Updates
DateUpdate(s)
7 June 2024Added new section, European Medicines Agency post-authorisation procedural advice for users of the centralised procedure
16 May 2024Section Commission proposes new measures for the better lifecycle management of medicine authorisations updated to confirm Commission adoption of the delegated regulation on 11 March 2024.
30 Apr 20241) Heading of section entitled Report from the CMDh meeting held on 19 – 20 March 2024 updated to Report and minutes from the CMDh meeting held on 19 – 20 March 2024
2) Link added to minutes from the meeting
3) Items nos 3 and 4 added to the section.
4 April 2024Links added to the published documents under the following sections:
1. Procedural advice on Zero Day MR Procedures
2. Pharmacovigilance Legislation
29 Mar 2024The following new sections were added:
i) eCTD v4.0 EU M1 Implementation Guide – draft Version 1.1 now available
ii) Update on new fee regulation (highlight from the EMA management board meeting, March 2024)added.
28 Mar 2024New section Report from the CMDh meeting hold on 19 – 20 March 2024 added.
25 Mar 2024The following new sections were added:
i)CTCG Best Practice Guide for sponsors of multinational clinical trials with different Part I document versions approved in different Member States under the Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014
ii) Annex Cover Letter Template vs. 4.0 adopted at CTCG plenary March 6 2024
22 Mar 2024New section Report and minutes from the CMDh meeting hold on 20-22 February 2024 added.
18 March 2024Added the folowing new sections:
1) Useful factsheets
2) Commission proposes new measures for the better lifecycle management of medicine authorisations
3) EMA Eudravigilance Registration manual and documents
11 Mar 2024Added new section CMDh annotated QRD template for MR/DC procedures (Based on version 10.4 of the QRD template for CP)