Last updated: 7 January 2024
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Minutes and presentations from the 20 November 2024 meeting with Interested Parties
You can view the minutes of the meeting here and most of the presentations from the meeting at the links below:
CMDh – SOS WG activities
CMDh – Amended Variation Regulation
AESGP-EUCOPE-Medicines for Europe – Implementation of the Variation Regulation
CMDh – Zero Day MRP
AESGP-EFPIA-Medicines for Europe – Key Information Section (KIS)
Information from two topics of the meeting is provided below.
Feedback from the Safety Outcome Survey (SOS) WG
Feedback was provided feedback from the discussions in the Safety Outcome Survey (SOS) WG,including the new approach on “other considerations” in PSUSAs and publishing the outcomesof safety variations.
- With regard to the new approach on “other considerations” in PSUSAs, Interested Parties were informed that relevant information on extrapolation of PSUSA outcomes from monocomponent to fixed-dose combination products (and vice versa) or on drug-drug-interactions will be published in the CMDh minutes, as appropriate.
- However, absence of the information on possible relevance of the outcome to other products in the CMDh minutes does not exempt MAHs from their obligation to continuously re-evaluate current scientific knowledge and keep their marketing authorisation updated.
- Feedback was also provided from a dedicated meeting with representatives of Interested Parties to discuss the publication of outcomes of safety variations on 14 November 2024.
- Mixed feedback from Interested Parties was received with regard to the need to have a published safety summary.
- It was clarified that no literature reference would be included in the safety summary, just high-level information if a change was based on literature.
- Following the dedicated meeting, Interested Parties were asked to provide further feedback on the initiative in writing to the CMDh secretariat by 10 January 2025.
- The group was also informed that the development of a web-based application for a database of list of safety concerns has been delayed due to other priorities.
- However, user acceptance testing (UAT) should start soon with the aim to go into production mode inearly 2025. Further information will be provided before the start of the UAT.
Implementation of the Variation Regulation
Medicines for Europe, AESGP and EUCOPE gave a joint presentation including questions on
the update of the CMDh procedural guidances and the implementation of the amended
Variation Regulation (Regulation (EU) 2024/1701 of 11 March 2024) (specifically on Type IA
submissions via annual update, annual update exceptions and mandatory worksharing),
including suggestions for transition period.
- AESGP asked for further clarification on how detailed a justification for grouping has to be given in the LoI for Worksharing variations, if the acceptance can only be confirmed after receipt of the complete application during the validation phase and how to get clarification for more complex cases.
- It was stated that the justification is checked at the stage of the LoI.
- However, for complex cases further information, e.g. on the products involved and if all changes apply to all products, must be be available.
- Generally, groupings that follow the agreed published examples should be acceptable.
- More complex cases should be further discussed with the reference authority.
- It was further clarified that supergroupings of Type IA variations can be submitted at any time from 1 January 2025.
- The 9-month deadline from the implementation of the first Type IA variation only applies to the annual update of Type IA variations.
- Medicines for Europe stressed the challenges with submitting annual updates 9 months after the implementation of the first change and asked for further clarification in case a variation in the annual update is rejected.
- A submission after 9 months is allowed, however it was stated that the expectation is that companies submit the annual update close to 12 months from implementation of the oldest variation in the set, but ultimately within the 9-12 month window afforded to MAHs.
- It is not expected that Type IA variations included in an annual update will be rejected.
- Additionally, it has been included in the exceptions that rejected Type IA variations from annual updates can be resubmitted as individual Type IAs immediately (outside of an annual update).
- The previous upgrade of Type IA to IB by some MSs for late submission will be further discussed (e.g. to keep the variation as IA if the annual update including that variation was submitted on time).
- Medicines for Europe acknowledged the need to include all concerned products in the AF rather than in an annex but stressed the technical limitations of the form when it a large number of products are involved.
- Medicines for Europe also acknowledged that 3rd countries that rely on EU decisions should accept the changes in the EU legislation.
- However, in the short term the annual update could create problems.
- It was suggested that further communication with these countries could take place to raise awareness to the updated EU variations framework.
- Following a question from EUCOPE, it was clarified that where a variation is applicable to different marketing authorisations from the same holder a worksharing procedure is expected.
- Specifically, quality variations for products with the same API are expected as a worksharing procedure however they may be submitted in a phased approach if these changes are not concomitantly applicable to different marketing authorisations from the same holder.
- It was further noted that a case-by-case approach may be needed for such cases. e.g. if an ASMF with the same version number is updated, this should be submitted via worksharing, unless product specific assessment is necessary.
- If a phased approach is followed, it is not expected that the variation is resubmitted in MSs where it has already been approved, but it is recommended that e.g. the same reference authority is used to ensure consistency in the assessment.
- CMDh confirmed that although not specified in their guidance, Type IA variations implemented before 1 January 2025 can still be submitted as single type IA variations according to the current rules also when only submitted in 2025. This is in line with EMA guidance.
Source: CMDh
Industry Q&A Clinic on post authorisation procedure management in IRIS
This webinar was held on 11 December 2024. You can view it here.
Source: EMA
Report from the CMDh meeting held on 10-11 December 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 from the above meeting includes (but is not restricted to) the following items:
1. Amended Variation Regulation
Amended Variation Regulation MAHs are reminded that the Variation Regulation 1234/2008/EC, as amended, as well as the correspondingly updated guidance documents by CMDh will become applicable as of 1 January 2025 and have to be regarded for all variation applications submitted after that date and, resp., for type IA/IAIN notifications that are implemented by the MAHs in their internal databases from that date on.
- Type IA/IAIN notifications already implemented in 2024 may be submitted according to the old rules also during 2025.
- As of January 2025, the updated variation guidance documents (currently published under “Procedural Guidance > Variations > Amended Variation Regulation”) will be moved to the main guidance part of the CMDh website, as applicable (mainly under “Procedural Guidance > Variations”).
You can read more about the amended Variation Regulation in this post.
2. N-nitroso-2,4-thiazole amine detected in ritonavir-containing medicinal products
N-nitroso-2,4-thiazole amine (NNTA; N-((2-isopropylthiazol-4-yl)methyl)-N-methylnitrous amide) has been detected in some ritonavir containing medicinal products in the EU/EEA.
- The Acceptable Intake (AI) was set at 18 ng/day. This limit has been published on 1 September 2024: Appendix 1: Acceptable intakes established for N-nitrosamines.
- Due to the potential criticality of ritonavir, it is considered important to gather further information about the possible impact to other ritonavir containing products.
- Therefore, MAHs of ritonavir containing products are requested to submit a step 2 response including confirmatory testing results as a matter of priority to all national competent authorities where the respective product is authorised, following the principles as described in the CMDh practical guidance for Marketing Authorisation Holders of nationally authorised products (incl. MRP/DCP) in relation to the Art. 5(3) Referral on Nitrosamines.
3. Transition of EMA post-authorisation procedures to the IRIS platform, training materials and feedback request
Please be aware of important information to ensure preparedness for the upcoming transition of EMA post-authorisation procedures to IRIS.
i. What will happen as of January 2025?
From January 2025, the post-authorisation EMA-led procedures (detalied below) will transition to IRIS for all Centrally Authorised Products (CAPs) (and involved non-CAPs i.e. NAPs, MRPs, DCPs for those procedures where EMA acts as reference authority) for procedures submitted on/ after 20 December 2024 via the current submission systems (i.e. Gateway and PSUR repository).
Kindly note that the submissions steps will still be done via the current systems, i.e., Gateway and PSUR repository, while IRIS will be used for procedure management only.
Which Post-authorisation procedures are transitioning IRIS:
The post-authorisation procedures transitioning to IRIS are:
- Variations; Article 61.3 notifications;
- Marketing Authorisation (MA) Transfers
- Periodic safety update reports (PSUR)*
- Post-authorisation measures (PAM)
- Annual reassessments
- Referrals
- Post-authorisation safety study (PASS)
- Postmarketing surveillance studies (PMSS)
- Line extensions
- Renewals
* Periodic safety update reports (PSUR) will transition to IRIS with the procedures starting on the 6 February 2025 and onwards as per PSUR procedural timetable published on EMA website
ii. Supporting documents
Please find in the attachment essential details to support the transition:
1. Actions for MAHs before the transition
2. Key training resources for MAHs
3. Service desk triage to request support
iii. Readiness survey
CMDh would appreciate to receive insights from each MAH on their level of readiness for the transition to IRIS and on the type of support needed. Based on the feedback received, additional engagement activities may be planned.
Kindly provide your feedback by replying to the enclosed survey by 7 January 2025.
iv. Next planned live Q&A sessions
Q&A clinics on post autorisation procedures are being organised in December 2024 and January 2025 as follows: –
19 December 2024 (11:00 – 12:00 CET): Register here
8 January 2025 (14:00 – 15:00 CET): Register here
17 January 2025 (10:00 – 11:00 CET): Register here
4. Meeting with representatives of Interested Parties
The CMDh convened a meeting with Interested Parties on 20 November 2024.
- The topics on the agenda included
- an update from the CMDh Safety Outcome Survey (SOS) WG
- implementation of the Variation Regulation (Regulation (EU) 2024/1701)
- the new Regulation on fluorinated greenhouse gases (Regulation (EU) 2024/573),
- environmental risk assessment
- 0-day MR procedures and the key information section (KIS) for the package leaflet.
- All presentations and the adopted minutes will be published on the CMDh website under “About CMDh > Contact with Representative Organisations
- A link to the presentations will be provided when they become available
Updated Q&A Obligation to inform in case of interruption or discontinuation of supply
This is an updated version (Rev 1 Dec 2024) of the Q & A document entitled The information obligation in case of interruption or discontinuation of supply of certain medical devices and in vitro diagnostic medical devices.
It has the following updates:
- Table of Contents: update of footnote 2
- Q&A no 8: update of footnote 8
- Q&A no 11: update of footnote 11
- Q&A no 12: addition of footnote 12
Source: European Commission
New fee regulation: webinar for industry stakeholders (human)
On 7 February 2024, the European Parliament and the Council adopted Regulation (EU) 2024/568 on fees and charges payable to the European Medicines Agency (‘New Fee Regulation’).
- The regulation will come into force on 1 January 2025.
- To support industry stakeholders on the upcoming changes resulting from the New Fee Regulation, the Agency hosted a webinar on 24th October 2024.for the human pharmaceutical industry.
- You can read more about the webinar here and you can view it here.
Source: EMA
European Shortages Monitoring Platform (EMSP)
The European Shortages Monitoring Platform (ESMP) has now gone live with a core set of functionalities.
- This digital platform is an important deliverable of the Agency’s extended mandate, enabling the quick and efficient exchange of information between regulators and pharmaceutical companies on shortages of medicines.
- It is also a major milestone in the effort to tackle medicine shortages and ensure that medicines are available to patients when and where they need them most.
Source: EMA
COMBINE programme for clinical trials and medical devices endorsed by Member States
National authorities in Member States have endorsed a new strategy for the COMBINE programme, a cross-sector initiative to streamline combined studies of medicines and medical devices, including diagnostics.
- The COMBINE programme will be rolled out over the coming years through seven cross-sector projects.
- It aims to foster collaboration between national authorities responsible for clinical trials and medical devices, as well as the Commission, European Medicines Agency, ethics committees and stakeholders such as sponsors, clinicians, and patient representatives.
Among the goals of this programme are to:
- Pilot a single assessment process for multi-country combined studies across device and medicinal product regulations
- Harmonise serious adverse event reporting processes
- Clarify questions on the interface between clinical trials and medical device regulations
- Explore new opportunities for advising sponsors and facilitating knowledge exchange among national authorities
The strategy can be found on the Commission’s webpage: Combined studies and COMBINE strategy.
Source: European Commission
Successful ePI pilot paves the way for implementation
The report of a pilot exploring the creation and testing of ePIs (electronic product information) in real regulatory procedures was published today.
- The pilot found that the EU regulatory system is generally prepared for the introduction of ePI and can move towards its phased implementation in regulatory procedures, while first recognising the need for more development, including additional functionalities and integration with current IT systems.
- Work on this additional development will be carried out in 2025.
- After this, the report recommends a phased approach to implementation beginning with voluntary adoption for centrally authorised products, and progressively expanding to nationally authorised products based on Member States’ readiness and available resources.
- The introduction of product information in an electronic format (ePI) compatible with digital platforms opens new possibilities for patients and healthcare professionals to access and interact with vital, up-to-date information about their medicines.
- The report looked at key indicators such as time taken to create ePI, the percentage of ePIs successfully created and published, usability of the IT tools and usefulness of guidance materials.
- This helped identify recommendations on future work required to enable the introduction of ePI into current regulatory processes.
- The recommendations call for enhanced guidance to support users, as well as updates to business processes to integrate ePI alongside existing practices with minimal disruption.
Source: EMA
Updated guidance documents
| Document | Revision/Version | |
|---|---|---|
| Good practice guidance for communication to the public on medicines’ availability issues | Revision 1 | This document provides EU national competent authorities and EMA with key principles and examples of good practices for communication to the public on shortages for human and veterinary medicines, as well as availability issues due to revocations or cessations of marketing authorisations. The document is intended for guidance only. Implementation should be a matter for EMA and EU national competent authorities, taking into account available resources and the communication needs within their territory. |
| EMA procedural advice for medicinal products intended exclusively for markets outside the European Union in the context of co-operation with the World Health Organisation (WHO) | Revision 4 | This document addresses a number of questions that users of EU-M4all may have. It provides an overview of the EMA’s position on issues that are typically addressed in pre-submission meetings. |
| European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure | This integrated version has been created for printing purposes only. Please refer to the individual question & answers as published in the pre-submission guidance for access to the hyperlinked information. | This guidance document addresses a number of questions which users of the centralised procedure may have. It provides an overview of the European Medicines Agency’s position on issues, which are typically addressed during the course of pre-submission meetings |
| European Medicines Agency post-authorisation procedural advice for users of the centralised procedure | Revision 110 | This guidance document addresses a number of questions which marketing authorisation holders (MAHs) may have on post-authorisation procedures. It provides an overview of the Agency’s position on issues, which are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. |
| Product Management Service (PMS) – Implementation of International Organization for Standardization (ISO) standards for the identification of medicinal products (IDMP) in Europe | Version 2.2 | This document provides detailed guidance on the data elements and associated business rules applicable to: • the submission of information of authorised medicinal products for human use; • the maintenance of authorised medicinal product data previously submitted. to the Product Management Service (PMS) only in accordance with the International Organisation for Standardisation (ISO), Identification of Medicinal Products (IDMP). |
| European Medicines Agency procedural advice for users of the centralised procedure for similar biological medicinal products applications You can view the track changed version of the document here. | This integrated version has been created for printing purposes only. Please refer to the individual Question & Answers as published under ‘Pre-authorisation’, ‘Regulatory’ section on the Agency’s website for access to the hyperlinked information. | This document addresses a number of questions which users of the Centralised Procedure may have. It provides an overview of the EMA position on issues, which are typically addressed during the course of Pre-Submission interactions/meetings. |
| European Medicines Agency procedural advice for users of the centralised procedure for generic/hybrid applications You can view the track changed version here. Source: EMA | This integrated version has been created for printing purposes only. Please refer to the individual Question & Answers as published under ‘Pre-authorisation’, ‘Regulatory’ section on the Agency’s website for access to the hyperlinked information. | This document addresses a number of questions which users of the Centralised Procedure may have. It provides an overview of the EMA position on issues, which are typically addressed during the course of Pre-Submission interactions/meetings. |
| European Medicines Agency guidance for applicants seeking scientific advice and protocol assistance You can view the track changed version here. Source: EMA | Revision 15 | This guidance document addresses a number of questions that users of the scientific advice or protocol assistance procedures may have. |
A common EU approach to data transparency in medicine regulation
EMA and HMA (Heads of Medicines Agencies) have published a comprehensive overhaul of their guidance on the identification of commercially confidential information (CCI) and personal data in marketing authorisation applications for human medicines.
This guidance applies to medicinal products for human use. It can be applied by analogy to veterinary medicines, until EMA and HMA have developed similar detailed guidance for veterinary medicines, which is planned for 2025.
- The update reaffirms the commitment of regulatory authorities across the European Economic Area (EEA) to extensive transparency when disclosing information, both in response to access-to-documents requests and in the proactive publication of data once a medicine is authorised.
- Instead of applying a ‘yes / no’ rule as to whether an entire section of the dossier can be released, the updated guidance considers information as releasable by default.
- It provides detailed practical orientations as to which specific points could be redacted or anonymised within each section of the dossier.
- The annex of the guidance document has been updated and now includes examples of information that may be considered CCI or protected personal data.
- The guidance also sets out how personal data will be protected if it can lead to the identification of a person.
- In doing so, it now considers the more recent EU legislation on data protection, namely the EU General Data Protection Regulation (GDPR) and Data Protection Regulation for the European Union institutions, bodies, offices and agencies (EUDPR).
- The document gives further guidance on how to identify personal data relating to experts, staff or patients, which should be anonymised.
Source: EMA
Update on the start of strongly recommended use of web-based eAF for NCA submissions
The expected start date of the strongly recommended use of the PLM Portal web-based eAF submissions to the National Competent Authorities for non-CAPs variations is now planned for February 2025. This updated timeframe is based on the latest projections by EMA’s development teams.
- Please note that the web-based eAF is fully functional for the submission of variations for CAPs, including EMA-led worksharing variations containing non-CAPs.
- Should you have any questions or require further information, please message plm.valuestream@ema.europa.eu.
Source: eSubmission
eSubmissions Gateway – naming of the working documents folder
When submitted with an eCTD, the Working Documents should always be provided in a separate folder called “xxxx-workingdocuments” on the same submission zip package containing the eCTD, where the number (xxxx) matches the number of the eCTD sequence being submitted.
- Any deviation will lead to a failed submission, and the package will have to be resubmitted with the correct naming. For example, if sending sequence “0007”, which contains working documents, the separate folder should be named “0007-workingdocuments”.
- More details can be found in chapter 2.9.10 of the Harmonised guidance eCTD – version 6.0.
Source: eSubmission
EU Harmonised technical eCTD guidance version 6.0 now available
A new updated version of the eCTD EU Harmonised technical guidance is now available here, together with the Release notes.
The EU Harmonised technical guidance is aligned with the EU M1 eCTD Specification v3.1 and the Validation Criteria v8.1.
The timeline for implementation is as follows:
- (optional use): From 1 December 2024 eCTDs compliant with EU M1 v3.0.4 or v3.1 and validation criteria v7.1 or v8.1 are accepted.
- (mandatory use): From 1 March 2025 only eCTDs compliant with EU M1 v3.1 and validation criteria v8.1 are accepted.
Source: eSubmission