Last updated: 29 May 2025
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Report from the CMDh meeting held on 20-21 May 2025
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. Questions and Answers on nitrosamines
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 10 and Q&A 22 have been updated to clarify the applicable AI limit to different administration routes and accepted in vivo study type and to highlight the expectations for the submission of variations to shelf-life and storage conditions as needed to comply with the interim limit during CAPA implementation.
- The new Q&As have been published on the EMA website and a link is provided from the CMDh website under “Nitrosamine impurities”.
- You can also view the updated Appendix 1: Acceptable intakes established for N-nitrosamines here.
Source: EMA
2. Phasing out of the Rabbit Pyrogen Test
In the context of Directive 2010/63/EU, which establishes measures for the protection of animals used for scientific and educational purposes, with the final aim of replacing all animal research with non-animal methods and which lays down principles of replacement, reduction and refinement (3Rs), EMA has published guidance for phasing out the Rabbit Pyrogen Test.
- This follows the revision of the European Pharmacopoeia, which includes the introduction of a new general chapter, 5.1.13 Pyrogenicity and the removal of references to the Rabbit Pyrogen Test from 57 existing monographs.
- The new and revised texts will be published in Supplement 11.8 of the Ph. Eur., with an
- implementation date of 1 July 2025.
- As a result, the use of the Rabbit Pyrogen Test will no longer be required in any text of the European Pharmacopoeia and it will be the responsibility of medicine developers to select a suitable in vitro test to control the pyrogenicity of their product, based on a risk
- assessment as described in the new general chapter 5.1.13.
- Applicants/Marketing Authorisation Holders are reminded that EU law makes specific reference to the mandatory character of the European Pharmacopoeia’s monographs in Directive 2001/83/EC on medicines for human use.
- Therefore, to comply with these changes, Applicants/Marketing Authorisation Holders should remove the Rabbit Pyrogen Test from their Marketing Authorisation dossiers and assess the need for a method replacement.
- In this regard, relevant guidance has been published by the EMA in the Question and Answer on the Removal/Replacement of the Rabbit Pyrogen Test from the Marketing Authorisation dossier.
- The guidance is applicable to both centrally and nationally authorised medicinal products for human use.
National information on MAH transfers
Here is a link to the document with the above title.
Updated PLM Portal eAF Release notes now available
An updated version of the PLM Portal eAF Release notes reflecting bug fixes and updates to web eAF made in the version 1.2.0.5 released to production on 26 May 2025 are now available on PLM Portal and on the PLM Portal eAF web page.
Recommended use of web-based Human variations electronic Application Forms (eAFs) for non-CAPs
Following the launch of optional use in February 2025, EMA now recommends the use of the PLM Portal web-based eAF for all non-CAPs human variations, where possible. This is aligned with the timeline and the roadmap towards mandatory use of the PLM Portal web-based eAF for all human variations.
- Note that the interactive PDF eAF remains available for use for all variation procedures and while the PLM Portal eAF is now recommended for use for all procedure types, there are some technical limitations, and in these cases you might need to use the interactive pdf forms. Consult the guidance and the release notes.
- Please report any production issues through the EMA ServiceDesk – Incident. Any change request or other generic questions, recommendations, improvement suggestions please raise them through EMA ServiceDesk – Request.
Source: eSubmissions
Updated PLM Portal eAF Release notes now available
An updated version of the PLM Portal eAF Release notes reflecting bug fixes and updates to web eAF made in the version 1.2.0.4 released to production on 13 May 2025 are now available on PLM Portal and on the PLM Portal eAF web page.
Additionally, the PLM portal FHIR XML version was updated to 2.2.2. The new version introduces the following change: there is a new element in the Organisation, called “alias”, which contains (if existing) the selected alternative company name: <alias value=”alternative company/organisation name” />
The Release notes can be found here.
Source: eSubmission
External guidance on the implementation of the European Medicines Agency Policy 0070 on the publication of clinical data for medicinal products for human use
Version 1.5 of the above document (May 2025) has been published. You can view a summary of the changes in this document.
Policy 0070 entered into force on 1st January 2015. Phase 1 of the policy pertains to publication of clinical reports only. Clinical reports and IPD are collectively referred to as “clinical data”. This guidance has been prepared to assist applicants in preparing packages for publication and the general principles applied.
Source: EMA
Plasma Master File (PMF) requirements. Questions and Answers for PMF Holders
This guidance in the format of a Q&A supplements the data requirements in the published guidelines on PMF scientific requirements (EMEA/CHMP/BWP/3794/03) and dossier requirements on PMF epidemiological data (EMA/CHMP/BWP/548524/2008) on topics related to information on blood establishments and blood/plasma centres (BE/BCs) to be included in the PMF as well as listing of prospective BE/BCs in Annex II of the PMF.
This Q&A describes the approach to be applied in the evaluation of the compliance of BE/BCs registered in PMF applications, with the aim to improve and harmonise the PMF content at submission and consequently to streamline the PMF certification and evaluation timelines.
Source: EMA
eAF v1.27.0.1 (Human Variation, interactive PDF) now available, for use from 1 May 2025
A new version of the interactive PDF Human Variation eAF v.27.0.1 was published on 6 May 2025, bringing a small change in the exported XML data. No other changes are introduced. It is highly recommended to use this latest version of the form.
Reminder:
- A new version of the Human Variation eAF v1.27.0.1 is now available on the eAF website. The version should be used starting from 1 May 2025.
- The version allows the selection of Reference Member State and Concerned Member State(s) when the type of authorisation is ‘National Authorisation’ and the type of application is ‘Super-grouping’.
- It is mandatory to use version 1.27.0.1 for all new Human Variation procedures.
- The version 1.27.0.0 for Human Variations will be removed from the eAF website, however, users can continue to submit applications using this version for ongoing procedures.
- Applicants are reminded that the version of the form should not be changed during an ongoing procedure.
Source: eSubmissions
SPOR status update
This webinar held on 4 April 2025 provides a status update on SPOR (Substances, Products, Organizations and Referentials data) and XEVMPD (Extended EudraVigilance Medicinal Product Dictionary).
Here’s a breakdown:
- Webinar Logistics: The session is recorded and available on the EMA website and YouTube channel [00:35]. Participants can ask questions via Slido using a provided code [01:12].
- SPOR and XEVMPD Overview: The webinar explains how SPOR, XEVMPD, and PMS (Product Management Service) fit together [04:20]. Data entered in XEVMPD is synchronized with PMS and shared with other processes [06:07]. If you need any substance, organization, referential data, you should request it in SMS and RMS ahead of XEVMPD submissions [06:36].
- Webinar Structure: The agenda includes updates on SMS (Substance Management Service), MS (Organization Management Service), RMS (Referentials Management Service), XEVMPD, and PMS [04:41]. Each topic has a short presentation followed by a Q&A session [04:49].
- Feedback and Improvements: The EMA seeks feedback on the webinar format and content [07:40]. They also conduct a customer satisfaction survey [08:13]. Suggestions include running the survey for a longer period [12:12].
- Substance Updates: There will be more substances with SVG flag zero in the future [23:09]. Changes to substance preferred terms are currently on hold due to potential impacts on pharmacovigilance activities [23:31].
- Synchronization Issues: EMA is analyzing synchronization issues between XEVMPD and PMS and working on implementing reporting to track it [02:18:48].
- Pharmaceutical Form Terms: Non-current terms in RMS without a current replacement in XEVMPD are maintained unless the National Competent Authority (NCA) wants to change them [02:19:47].
- PMS API Updates: Updates via the PMS API might be available later, potentially in 2026 [02:21:11]. Data submitted through the PMS product UI will be available in the PMS API [02:21:54].
- Webinar Feedback: The EMA acknowledges feedback about the webinar being information-heavy and is exploring ways to improve, such as shorter, crisper sessions with additional webinars for in-depth discussions [22:34].
- Upcoming Event: The next event is the PMS info day [23:33].
Public System Demo Q1 2025
This webinar was held by the EMA on 26 March 2025. Time stamps are provided below.
00:00:00 – Welcome / Introductions
0:05:19 – Data Analytics Platform (DAP) – Trial Map
0:26:05 – Product Management Services (PMS) and Product User Interface (PUI)
1:07:59 – Electronic Product Information (ePI)
1:37:59 – Electronic Application Form (eAF)
2:02:51 – Union Product Database (UPD)
2:17:30 – Closing remarks and date of next demo
Source: EMA
Report and minutes from the CMDh meeting held on 23-24 April 2025
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. Public consultation on QRD template version 11 and package leaflet key information
EMA is inviting all interested stakeholders to comment on a public consultation on version 11 of the quality review of documents (QRD) template and on the potential inclusion of a ‘key information section’ in the package leaflet of centrally authorised medicines.
- The CMDh would like to encourage stakeholders to comment bearing in mind that the QRD template for MR/DC procedures is based on the QRD template for centrally authorised medicines.
- The deadline for comments is 31 May 2025 for the package leaflet key information and 31 August 2025 for the QRD template v11.
- The public consultation documents and instructions for submitting comments are available on the EMA website.
- Alternatively, you can view further information on this page of the blog under the section Consultations – Medicines
2. Template for Request for MRP/RUP
Following the implementation of the new Guideline on the environmental risk assessment of medicinal products for human use, MRP/RUP requests submitted until 31 March 2025 had the possibility to provide a commitment to submit a variation within 3 months after end of MRP/RUP, in case the ERA provided in Module 1.6 was not in line with the current version of the Guideline.
- Considering that this deadline has now passed, the CMDh agreed an update of the template for Request for MRP/RUP to delete this option and further clarify that if the dossier does not contain a Module 1.6 or the ERA provided in Module 1.6 is not in line with the current version of the Guideline, a variation has to be submitted to add/update Module 1.6 prior to the MRP/RUP.
- In line with the above, a similar statement has been included with regard to the RMP requirement.
- The updated template has now been published on the CMDh website under “Templates > MRP/RUP”
- Here, you can view the track changed (September 2024) and clean (April 2025) versions of the template
- It was reiterated that marketing authorisation applications submitted before 1 September 2024 do not have to comply with the current version of the guideline and CMDh members were asked to convey this message in their NCAs.
3. Nitrosamines step 3 CAPA implementation
The deadlines established in the framework of the Call For Review (CFR) (Step 1, 2 and 3) for
medicines containing chemically synthesised and biological active substances marketed in the
EU/EEA have elapsed.
- For step 1 and 2 responses a high compliance rate has been observed.
- MAHs are reminded of their responsibilities to ensure the quality, safety and efficacy of their medicines and to adhere to the nitrosamines guidance outlined by the EMA and the CMDh(Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities inhuman medicinal products). This includes the obligation to monitor and mitigate nitrosaminerisks throughout the lifecycle of their products in line with Article 23 and Annex I of Directive2001/83/EC and Article 16 of Regulation (EC) No 726/2004, to ensure their medicinal products are manufactured and controlled by means of processes and methods in compliancewith the latest state of scientific and technical progress.
- Any MAHs that have not notified the outcome of the risk assessment for the identified nitrosamine impurities to the relevant competent authority should do so as a matter of priority, including any updates to previous notifications.
- The required templates for notification of step 1, 2 and 3 are set out 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.
- In case levels of N-nitrosamines are detected exceeding the AI, MAHs are expected to establish and implement corrective and preventive actions (CAPAs) in authorised medicines without any delays in order to ensure patients safety and product quality.
- The implementation of CAPAs and submission of CFR step 3 responses should be done at the earliest opportunity, but up to a maximum of 3 years from the establishment and publication of the AI.
- If companies become aware that they will not be able to bring their product into compliance within this 3-year period, these companies should reach out and inform the concerned authorities with detailed justification and timelines for completion of CAPAs.
- The compliance of the MAHs with the above-mentioned obligations for nitrosamines will be subject to market surveillance through regular controls by competent authorities including during inspections and additional market surveillance activities. Authorities in the EU will continue to take all necessary measures to protect patients and ensure that medicines in the EU meet the required quality standards.
4. Request for an additional year of market protection according to Art. 10(1)
The EC provided feedback on the question raised at the March 2025 CMDh meeting on
whether a medicinal product authorised under Article 8(3) of Directive 2001/83/EC can
benefit from an additional year of market protection when there are already medicinal
products previously authorised via an abridged procedure (Articles 10(1) and 10(3)), i.e.
under the same global marketing authorisation (GMA) (same company, same active
substance).
- The EC representative informed that similar questions were raised previously by the CMDv.
- It was also noted in the subsequent discussion that the scenario at stake is not specifically addressed in Directive 2001/83/EC or in the Notice to Applicants.
- However, it would need to be taken into account that Article 10(5) of Directive 2001/83/EC provides for the possibility that a well-established medicine receives protection (of 1 year) for the new indication with significant pre-clinical or clinical studies could be considered.
5. Electronic submission
The EMA informed the CMDh again about the intended move to ‘recommended use’ of the
PLM Portal web-based variation eAF in Q2 2025 for all procedures containing non-CAPs (i.e.
MRP/DCP/NP) where the interactive pdf eAF is currently used.
- MSs were asked to inform the EMA in case they experience issues with the use of the web-based variation eAF.
- Training on the new form is available in the EU NTC and the training can also be re-run, if needed.
- With regard to the inclusion of the integrity stamp in the new eAF, it was agreed to review the CMDh documents on national requirements, specifically with regard to the signature requirements.
- The documents will be uploaded in Sharepoint for MSs to review and update for further discussion in May/June.
- MSs were asked to provide feedback on the visibility of sections 4a, 4b and 4c, when not selected, until 9 May 2025.
- If no objections are raised, the sections will not be displayed, if empty.
- The EMA informed the CMDh that information text for an error message to applicants, when the MRP variation number has not been entered, has been implemented. Any issues related to the text can be raised to the EMA, as needed.
- Finally, the EMA will remove the word “importer” in the note in section 2.5.2. for CAPs. MSs were asked to inform the EMA if this information is needed for non-CAPs. If no objections are raised until 9 May 2025 the deletion will also be implemented for non-CAPs.