Last updated: 31 March 2025
To view updates, click on the ‘+’ sign below:
Update – MedEthicsEU report – Survey on National Part II Clinical Trial Application (CTA) requirements (March 2025)
Overview part II requirements in a Clinical Trial application by Member State
As of 31 January 2022, the clinical trial regulation EU no 2014/536 (CTR) is applicable in the EU/EEA.
- The CTR describes rules for the submission, assessment, start, conduct and closure of a clinical trial.
- In CTR annex I section K to R the documentation of part II is described.
- For each of these section a placeholder is provided in CTIS where the sponsor can upload the required documentation.
- There is an additional placeholder in CTIS for compliance on rules biological samples (not mentioned in annex I CTR but in article 7.1h of the CTR).
- This report provides an overview of the required part II documentation of 21 MS in EU/EEA.
- MedEthicsEU is still working to get the overview complete and to update the overview if there is a change in the MSC.
Source: European Commission
EMA Procedural Advice on Recommendations on unforeseen variations according to Article 5 of Commission Regulation (EC) No 1234/2008
MAHs can request a recommendation on the classification of an unforeseen variation, in line with Article 5 of the Commission Regulation (EC) No 1234/2008. This refers to a marketing authorisation variation that is not detailed in the European Commission guideline that highlights the various categories of variations, and that does not have a recommendation under Article 5.
Revision 4 (24 March 2025) of the above guidance has been published. You can view it here.
Source: EMA
Updated PLM Portal eAF guide to navigation now available
An updated version of the PLM Portal eAF guide to navigation is now available.
Source: eSubmission
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 1.2.0.1 released to production on 17 March 2025 are now available on PLM Portal and on the PLM Portal eAF web page.
Source: eSubmission
Clinical Trials Coordination Group (CTCG) updates
| Date | Document |
|---|---|
| CTCG Best Practice Guide for sponsors who have missed the transition timeline | Version 1 – January 2025 |
| Guide for Change of Trial Sponsor | Version 1 – February 2025 |
| CTCG’s developed a Simplified template of Annual Safety Report, Non-commercial sponsors conducting a single clinical trial on IMPs with a MAH in any of the EU /EEA member states and where the SmPC is used as RSI submitting this simplified ASR based on the ICH-E2F may be appropriate. This template gives detailed instructions on what information is expected and what may be omitted in this setting. The simplified ASR should always be written in English. | March 2025 |
Source: HMA
Q&A on QP declaration updated
Here, you can view the track changed (Dec 2021) and clean (Feb 2025) versions of the updated Q&A.
Source: HMA
Templates for Active Substance Master File (ASMF) updated
The following templates have been updated:
- Template for Active Substance Master File (ASMF) Type IB Variation Assessment Report– Here you can view the track changed (Jul 2010) and the clean (Feb 2025)versions of the template
- Template for Active Substance Master File (ASMF) Assessment Report (Applicant’s Part) (February 2025) – Here you can view the track changed (Jul 2010) and clean (Feb 2025) versions of the template
- Template for Active Substance Master File (ASMF) Assessment Report (Restricted Part) – Here you can view the track changed (Jul 2010) and clean (Feb 2025) versions of the template.
PLM Portal eAF – Integrity went live on 6 March
The PLM Portal eAF Integrity stamp feature was deployed Thursday, 6th of March, after 18:00 CET.
The main impact and changes are as follows:
- Upon ‘Finalisation’, the PLM Portal web based human variation eAF will be locked and moved to the ‘Completed’ tab (the form can be opened for further editing if necessary)
- The form will be locked with a digital ‘signature’ called eAF integrity warranty (or eAF integrity stamp)
- Was launched on 6th March 2025 – after this date the system will include the stamp on all forms that are finalised
- Forms that have not been finalised (i.e. do not contain the integrity stamp) will be rejected by the regulators in the future – date to be confirmed!
- The applicants will still be able to include additional digital signature(s) into the finalised form (exported pdf)
- It will not be possible to include an image of a signature or an ‘adobe signature’ to the form after the stamp is included
Source: eSubmission
Report and minutes from the CMDh meeting held on 25-26 February 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. Templated end of procedure
The CMDh agreed an update of the template for End of Procedure (EoP) for DCP.
- The document has been updated to reflect that the EoP template will only be used in case of agreement between Member States.
- It was agreed that in case of disagreement among Member States, the referral notification will be circulated instead of the EoP template.
- The updated document has now been published on the CMDh website under “Templates > DCP (AR/Comments)”.
- Here, you can view the track changed (Jan 2022) and clean (Feb 2025) versions of the document.
2. CMDh guidance documents related to the Paediatric Regulation
The CMDh agreed to an update of the following documents:
- The Best Practice Guide for Article 45 and 46 paediatric worksharing procedure.
- The Questions and Answers on the Paediatric Regulation.
- Cover letter for submission of information about Article 46 paediatric studies.
- The main change is to update the process for Art. 46 worksharing of paediatric studies when updates to the product information are proposed by the MAH.
- It was agreed that when amendments to be introduced to the PI are identified by the MAH, a variation should be submitted containing the Article 46 paediatric study results, instead of starting an Art. 46 worksharing procedure.
- Other minor changes have been included (e.g. to remove references to the discontinued Paediatric Regulation WP).
- The updated guidance documents have now been published on the CMDh website under “Paediatric Regulation > Guidance Documents”.
- Here, you can view the track changed and clean (Feb 2025) versions of the Best Practice Guide for Article 45 and 46 paediatric worksharing procedure
- Here, you can view the track changed (Jun 2023) and clean (Feb 2025) versions of The Questions and Answers on the Paediatric Regulation.
- Here you can view the track changed and clean versions of the Cover letter for submission of information about Article 46 paediatric studies.
3. CMDh guidance documents related to variations
The CMDh agreed an update of the CMDh Best Practice Guide for the Processing of (Super-)Grouped Applications in the Mutual Recognition Procedure (Chapter 6).
- The main change to the BPG Chapter 6 is to include that for super-grouping procedures with purely NAPs or a mixture of MRP/DCP and purely NAPs, the eAF mentioning all products concerned will be uploaded in CTS in order to allow every MS concerned to identify the products included in the super-grouping correctly.
- This is in line with the current practice for worksharings in accordance with the BPG Chapter 7.
- In addition, minor corrections to the previous version have been included.
- The CMDh also agreed an update of the Examples for acceptable and not acceptable groupings for MRP/DCP products.
- It has been further emphasized that grouping of type IA and type IAIN notifications is only allowed within the context of the annual update or super-grouping in accordance with the amended Variation Regulation.
- This is in line with the information already included in the BPGs Chapters 3 and 6.
- The updated guidance documents have now been published on the CMDh website under “Procedural Guidance > Variation”.
- Here, you can view the tracked changed (Jan 2025) and clean (Feb 2025) versions of CMDh Best Practice Guide for the Processing of (Super-)Grouped Applications in the Mutual Recognition Procedure (Chapter 6).
- Here, you can view the track changed (Oct 2024) and clean (Feb 2025) versions of the Examples for acceptable and not acceptable groupings for MRP/DCP products.
4. Assessment report templates
The CMDh agreed to update all assessment report templates published on the CMDh website to remove the section ‘Names of the assessors’ that included the assessor’s contact details.
- The contact details of the RMS contact person will remain in the templates.
- This update follows the approach taken for the centralised procedures.
5. Two pharmaceutical forms in section 1 of the SmPC for one MA
The CMDh discussed how to handle generics of Reference Medicinal Products (RefMPs) that have historically been authorised with two pharmaceutical forms in section 1 of the SmPC, e.g. powder and solvent for solution for injection/infusion or oral solution, and where no combined EDQM standard term exists.
- The EMA reported from one case in the centralised procedure where an abridged application to an old RefMP (containing two pharmaceutical forms in section 1 of the SmPC) was authorised.
- In that case, it was agreed that the abridged application will not follow the pharmaceutical form description of the RefMP, but the updated EDQM rules were applied instead.
- In that case the primary/most “complex” pharmaceutical form was chosen for the abridged application and the alternative route of administration was mentioned in section 4.2 of the SmPC and the relevant sections of the labelling.
- The CMDh agreed by majority that for new MAAs section 1 and 3 of the SmPC should only include the main pharmaceutical form (form with the strictest requirements or the primary use).
- Additional routes of administration can be mentioned in section 4.2.
- Additional routes of
- administration may also be reflected in the product name nationally, if appropriate.
- The RMS will usually make a proposal for the main pharmaceutical form and this can be commented on by the CMSs.
- Complex cases may also be brought for discussion to CMDh.
6. Approving the national package leaflet mock-up as part of the national phase of MRP/DCP/ PL
The CMDh discussed if design and layout in the national language can be accepted as part of
the national step, if it is different from the design and layout of the leaflet of the MR/DC
marketing authorisation procedure, for which the readability has been tested and the report
of the study has been approved during the European phase of the procedure.
- Such a scenario can happen, e.g. if the company acting as MAH in a MS is a different entity/company than the applicant, and uses its own, distinctive corporate design of the leaflet.
- The CMDh agreed that, in case the design and layout differ significantly, the MAH needs to provide a bridging report (or user test), which is then assessed nationally.
- It was noted that in some MSs it is possible to assess a “house style” of the PL per MAH, which can then be applied to all products of that MAH.
7. Applicability of Art. 10(1) vs 10(3) of Directive 2001/83/EEC
The CMDh discussed a validation issue of a national application for an abridged application for
an oral suspension with an ERP authorised as film-coated tablets.
- The applicant claims Article 10(1) as legal basis would be appropriate, whereas the NCA considers Article 10(3) to be the most suitable legal basis for this case.
- The CMDh agreed that the pharmaceutical forms can be considered the same (immediate release oral formulations).
- However, there is a difference in the (expression of) strengths between the product applied for and the RefMP and, therefore, Article 10(3) should be used.
8. Assessment Report (AR) AR templates
A proposal was presented not to include names of assessors in assessment report templates in
line with the approach taken for the centralised procedures.
- The CMDh agreed to update all AR templates published on the CMDh website to remove the section ‘Names of the assessors’ that included the assessor’s contact details.
- The contact details of the RMS contact person will remain in the templates.
- The CMDh agreed with the proposal and the updated templates will be published on the CMDh website.
2024 – Statistics for New Applications (MRP/DCP), Variations, Referrals and Paediatric Worksharing procedures
You can view the statisitics here.
The main change in the document appears to be the addition of a clarification that it is not possible to include a type IA variation in the submission of a Type IAIN variation for one marketing authorisation.