Last updated: 31 January 2024
See updates at the end of the post.
Report and minutes from the CMDh meeting held on 12-14 December 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. Impurity chloromethyl isopropyl carbonate (CMIC) in tenofovir disoproxil-containing medicinal products
In February 2023 the CMDh published a letter on the CMDh website addressed to MAHs of tenofovir disoproxil-containing medicinal products approved via MRP/DCP, requesting the MAHs to put in place measures (if not already in place) to ensure that levels of CMIC are below the limit of 50 ppm in the active substance.
- In the letter, MAHs were requested to inform the national competent authority (in case of a purely national marketing authorisation) or the RMS (in case of an MRP/DCP product) of the strategy to implement this change including the current specification of CMIC impurity in the active substance within 3 months of publication of the letter.
- Impacted MAHs were required to submit a variation within 9 months of publication of the letter to ensure compliance with the above-mentioned limit.
- The submission via a worksharing procedure is strongly recommended, where applicable. As the deadline has now passed, concerned MAHs are reminded to submit the requested variation as soon as possible, if they have not already done so.
2. Updates to the Best Practice Guides (BPGs) (and Q &A ) for the submission and processing of variations in the Mutual Recognition Procedure
The CMDh agreed updates to several guidance documents related to variations as follows:
| Updated guide or Q & A | Links to documents | Reason for update |
|---|---|---|
| Chapter 6 CMDh BPG for the processing of Grouped Applications in the Mutual Recognition Procedure | Here, you can view the track changed (Dec 2022) and clean (Dec 2023) versions of the document. | The BPG has been revised to allow quality type IA notifications to be included in supergrouping, among other changes in the document. |
| Chapter 7: CMDh BPG on Worksharing | Here, you can view the track changed (July 2023) and clean (Dec 2023)) versions of the document. | The BPG has been updated to enforce the message that product-specific changes cannot be included in variation worksharing procedures. While the ‘present’ status can differ in the marketing authorisations included in the worksharing, the proposal and outcome must be the same for all products involved in the procedure. |
| The Q&A – List for the submission of variations for human medicinal products according to Commission Regulation (EC) 1234/2008 | Here you can view the track changed (Sept 2023) and clean (Dec 2023) versions of the document. | Question 4.9 has been updated to clarify that a change in the name/address of the MAH can be submitted as a single variation in MRP/DCP, in case the name/address is the same in the MSs concerned. A grouped variation is only needed if the name/address is different in each MS. |
The updated documents have been published on the CMDh website under “Procedural Guidance > Variations” and “Questions & Answers”, respectively.
3. Working Party on Variation Regulation
Among the items discussed, the WP WP also discussed cases where large, grouped quality variation applications were received resulting in a “new product” with a new quality dossier.
It was noted that the submission of a new marketing authorisation application is preferred if the complete quality dossier is modified (e.g. replaced by a complete new module 3). However, the WP agreed that there are no grounds for refusal of such variation applications (as long as the Reference Medicinal Product (RefMP) for generic applications is not changed).
4. Brexit
EMA provided an update on the implementation of Regulation (EU) 2023/1182 (Windsor Framework) for medicinal products for human use intended to be placed on the market in Northern Ireland and its regulatory impact on Centrally Authorised Products (CAPs).
- The main regulatory impact is foreseen for CAPs which will not be able to be placed on the market in Northern Ireland unless, amongst others, they have an authorisation by the competent authorities of the United Kingdom in accordance with the law of the United Kingdom and under the terms of the authorisation granted by them.
- Among other consequences, the labelling will need to be updated accordingly, multi-country packs with NI will no longer be valid and parallel distribution with NI will cease to be possible once the Regulation becomes applicable.
- To allow preparation of industry, EMA will publish Questions and answers to Stakeholders on the implications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use (i.e. excluding NAPs, veterinary medicines and products approved by MHRA under UK law).
[Post-meeting notes: The document Questions and answers to Stakeholders on the implications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use was published on 5 January 2024 and you can view it on this page.
5. TiO2 (E171) used as excipient
The interim 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 input from Interested Parties was sought and taken into consideration while preparing the feedback. The document was agreed by the CMDh and will be sent to the EC after the meeting.
Replacement of TiO2
The CMDh agreed that the change to remove or replace TiO2 cannot be submitted as type IAIN (B.II.a.3.b) since condition 9 is not considered fulfilled as the change is triggered by safety issues. The variation should therefore be submitted as type IB.
6. Harmonisation of marketing authorisations by requesting worksharing procedures
The CMDh discussed a proposal to start a pilot on requesting SmPC harmonisation via variation worksharing procedures for medicinal products that are disharmonised but are not suitable for an Article 30 referral.
- The proposal is based on actions included in the CMDh MAWP.
- The harmonisation of product information (PI) is also part of the European’s Commission pharmaceutical strategy for Europe.
- The pilot should mainly focus on the following disharmonised PI sections:
- Therapeutic indications,
- posology
- Method of administration and contraindications.
- Identified products should be brought to the CMDh for further discussion on whether a variation worksharing procedure to harmonise the SmPC should be requested.
- Further information on the handling of such a worksharing procedure is given in Q4.21 of the Q&As on variations.
- A proposal for a standard letter to MAHs was presented.
- The CMDh agreed to further explore the possibility of requesting SmPC harmonisation via variation worksharing.
- Based on the feedback from the MAHs, the pilot can be reviewed in the future.
- MSs were asked to comment on the proposal and the presented standard letter for further discussion in January 2024.
- It is also expected to discuss first examples in January 2024 .
- Once the process is more mature, it can also be presented in the next CMDh meeting with Interested Parties.
7. Data exclusivity of Art. 10a dossier when generic product is already authorised under the same GLobal Marketing Authorisation (GMA)
The CMDh discussed if a medicinal product authorised under Article 10a of Directive 2001/83/EC (well-established use (WEU)) can potentially benefit from data exclusivity and market protection when an Article 10(1) generic product is already authorised in the same global marketing authorisation (same company, same active substance. The CMDh agreed to send the questions to the EC
Product Lifecycle Management (PLM) Value Stream Deep-Dive Webinar
A webinar with the above title was held on 30 November 2023. YOu can view it here.
PLM is one of three value streams covering the product lifecycle implemented by the Agency as part of its agile transformation. PLM aims to digitally transform and optimise regulatory procedure management as well as data submission and reuse throughout the product lifecycle. The value stream works with EMA partners and stakeholders to deliver systems and services to manage the authorisation and lifecycle of medicinal products and medical devices within the Agency’s remit for the ultimate benefit of public health in the EU.
- The webinar was for those interested in learning more about what the Agency’s Product Lifecycle Management (PLM) value stream is working on and what it aims to achieve.
- aimed at illustrating the interconnections between the various digital products being delivered.
- In addition, further insights into the approach taken to enhance product lifecycle management technology in order enable more efficient and effective medicine regulation will be outlined.
Source: EMA
EMA & FDA Questions & Answers: Expediting Quality Development for FDA’s Breakthrough Therapies and EMA’s PRIME Programs
FDA and the EMA published the “EMA–FDA joint Q&As on Quality and GMP aspects of PRIME/Breakthrough therapy applications” document supporting quality development for FDA’s Breakthrough Therapy (BT) designation and EMA’s Priority Medicines (PRIME) scheme programs for patients with unmet medical needs.
The document is divied into the following four Annexes:
- Annex 1. Q&A on Control strategy considerations for PRIME/BT applications
- Annex 2. Q&A on Process validation approaches for PRIME/BT applications
- Annex 3. Q&A on Alternatives for determination of re-test period or shelf-life for PRIME/BT applications
- Annex 4. Q&A on GMP considerations for PRIME/BT applications
For EMA, these Q&As are applicable to chemical and biological medicinal products for human use, including complex biologicals (such as ATMPs), unless stated otherwise.
For FDA, these additional discussions and the resulting annexes are only applicable to CDER-regulated products. Therefore, all references in the annexes to biological products are intended to refer to CDER-regulated biological human drug products only. Center for Biologics Evaluation and Research (CBER) -regulated products, such as advanced therapy medicinal products (ATMPs), are not in the scope of these documents.
Source: FDA
Member states contact points for translations review
This document has been updated to v 6.4 of December 2023. You can view it here. The updates are not clarified in the document.
Data requested for Variations and/or Renewal Applications in the MRP/DCP which are not stated in the current EU legislation and/or in Volume 2B, Presentation and format of the dossier Common Technical Document (CTD) and/or in the EEA approved Guidelines/ Recommendation papers
Here, you can view the track changed (Nov 2023) and clean (November 2023) documents.
Source: CMDh
Guidance on paediatric submissions Via Syncplicity Web Client – Revision 7
This guidance has been updated to Revision 7 (November 2023). The changes to the document appear not to have been explained/listed in the document. You can view it here.
Source: EMA
Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of Risk Management Plans (main body and annexes 4 and 6) General guidance – Revision 1
This guidance has been updated to Revision 1 (November 2023). The changes to the document appear not to have been explained/listed in the document.
This document aims at giving general guidance to companies on the retention/removal of Protected Personal Data (PPD) and identification of Commercially Confidential Information (CCI). All the changes suggested in this guidance are of editorial nature and should be implemented in the Risk Management Plan (RMP) during the scientific review process prior to the Opinion and adoption of the final RMP version.
Source: EMA
Data Quality Framework for EU medicines regulation
This document is the first release of the EU Data Quality Framework (DQF) for medicines regulation and defines high-level principles and procedures that apply across EMA’s regulatory mandate.
- This framework provides general considerations on data quality that are relevant for regulatory decision making, definitions for data quality dimensions and sub-dimensions, as well as their characterisation and related metrics.
- It provides an analysis of what data quality actions and metrics should be considered in different use cases and introduces a maturity model to guide the evolution of automation to support data-driven regulatory decision making.
- This document is intended to be a general resource from which more focused recommendations can be derived for specific regulatory domains with specified metrics and checks.
Source: EMA
New submission unit to be used for requesting a Re-examination of an CHMP Opinion
An updated version of the eSubmission Gateway XML delivery file user interface will be available starting with 1 December 2023, 18:00 CET.
- This update introduces in the delivery file for Human submissions the option to choose “Re-examination” submission unit for various submission types.
- Use this unit for requesting re-examination of opinion for MAA, extension, Type II variation, renewal and annual re-assessment as well as Referral procedures
- Please note that regulatory guidance referring to how to send re-examination requests will be updated in the following period.
- Re-examination requests should be submitted via the eSubmission (Syncplicity) Gateway using eCTD format where required for the procedure type.
Source: eSubmission
Updated eAF v1.26.0.0 (Human MAA)
- Updated v1.26.0.0 Human MAA eAF is now available on the eAF website.
- The form is ready for immediate use. The change implemented in this version is a minor bug fix (related to Annex 5.19).
- It is strongly recommended to use this latest version (document properties date 27.10.2023).
- Please note that there is no version number change and that the release notes are published in the relevant section of the eAF webpage.
Updated version of the eAF v1.26.0.0 (variation and renewal)
An updated version 1.26.0.0 of the Variation and Renewal (both Human and Veterinary) eAF is available starting with 28 November 2023, 18:00 CET.
- A change has been implemented to allow Non-Current terms to be selected in the “Pharmaceutiacal form” lists.
- It is recommended to use this latest form for new submissions. Please note that there is no version number change and that the release notes were updated and published in the relevant section of the eAF page.
Source: eSubmission
eCTD EU Module 1 Specification proposed changes now open for public consultation
The Human Harmonisation Group has analysed the change requests received upon opening the eCTD EU Module 1 Specification for review and has now published the draft documents for public consultation:
| Item | About the item |
|---|---|
| eCTD EU Module 1 Specification | Contains a summary of the proposed changes in the Document control table, and all the amendments are highlighted throughout the text with the track changes feature. |
| eCTD EU Validation Criteria | Contains a summary of the proposed changes in the Document control tab. |
| EU Accepted File Formats for eCTD |
Please submit your questions and comments via email to EUM1Spec@ema.europa.eu by the end of the day 12 January 2024.
Source: eSubmission
Updates
| Date | Update |
|---|---|
| 31 Jan 2024 | 1. Title of section Report from the CMDh meeting held on 12-14 December 2023 up dated to Report and minutes from the CMDh meeting held on 12-14 December 2023. 2. Link added to minutes from the meeting. 3. New Items 4, 5, 6 and 7 were added under the section. |
| 21 Dec 2023 | New section Report from the CMDh meeting held on 12-14 December 2023 added. |
| 20 Dec 2023 | New section section Product Lifecycle Management (PLM) Value Stream Deep-Dive Webinar added. |
| 19 Dec 2023 | Added the following new sections: 1) Section entitled Member states contact points for translations review 2) Section entitled EMA & FDA Questions & Answers: Expediting Quality Development for FDA’s Breakthrough Therapies and EMA’s PRIME Programs |