Last updated: 2 August 2024
To see updates, click on the ‘+’ sign below.
SPOR status update
This EMA webinar was held on 10 July 2024. It covers the following topics:
- SPOR, XEVMPD/PMS and other processes
- SMS Status update
- OMS Status update
- RMS Status update
- XEVMPD Status update
Source: EMA
Template for notified body confirmation letter of the status of a formal application, written agreement, and appropriate surveillance in the framework of Regulation EU 2024/1860
You can view the template here.
Source: European Commission
Clinical Trials Coordination Group (CTCG) Key Documents List – Template cover letters and RFI Response
Cover letters are essential documents providing relevant background information on the application, and a clear overview of what has been submitted in CTIS.
- A high-quality cover letter will facilitate validation and assessment.
- This also applies to the List of Changes to be submitted as a response to the RFI.
- The following templates appear to have been updated
Template | Version | About the template |
---|---|---|
Initial application cover letter | Version 1 July 2024 | To be used for the initial application (or resubmission) of new clinical trials. |
Substantial Modification (SM) – Cover letter | | Version 2 July 2024 | Provides background information on the SM application |
Modification description | Version 2 July 2024 | Provides an overview of all changes and submitted documents |
RFI Response List of Changes to the Application | Version 1 July 2024 | To be uploaded within each RFI – mandatory upload if changes are made to the application. |
Source: HMA
Blue box requirements
Here, you can view the track changed (May 2023) and clean (July 2024) versions of the requirements document.
Information session on MDR/IVDR for international regulators
An information session was held on 4 July 2024 for International regulators on the state of play of MDR/IVDR Implementation.
You can view the session from this page and view the slide deck here.
Product Management Service (PMS) Product UI training
Following the go-live of the Product Management Service (PMS) Product User Interface (UI) on 31 May 2024, the PMS team hosted a training session (see link below) to explain & showcase the access and navigation for Product UI as well as three Q&A clinics. Links to all 5 webinars are provided below.
Date | Webinar | Presentations |
---|---|---|
3 June 2024 | Product Management Service (PMS) Product UI training (access & navigation) | Agenda – Product Management Service (PMS) Product UI training (access & navigation) Presentation – Product Management Service (PMS) Product UI Training (Access & Navigation) |
6 June 2024 | PMS Product UI Q&A Clinic (1) | Questions and Answers – Product Management Service (PMS) Product UI training (access & navigation) Includes the Q&As from all four sessions. |
13 June 2024 | PMS Product UI Q&A Clinic (2) | See above |
20 June 2024 | PMS Product UI Q&A Clinic (3) | See above |
27 Jun 2024 | PMS Product UI Q&A Clinic (4) – 27 June 2024 | See above |
23 July 2024 | PMS Product UI and API Q&A Clinic |
Report and minutes from the CMDh meeting held on 25-26 June 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 on Multilingual packaging
The CMDh agreed an update of the Best Practice Guide on Multilingual packaging.
- The main change to the updated BPG document (Rev. 5) is to reflect the success of the Multilingual Packaging pilot which took place 2020-2024.
- To improve the availability of medicinal products in the EU, especially in so called “small markets”, the pilot facilitated the preparation of an ‘EU full/reduced harmonised labelling text’ during the EU procedural timelines to expedite the agreement of multilingual packs in the national phase of procedures.
- Due to the engagement with the pilot, it has now been agreed to move from a pilot basis to a standard process.
- Therefore, EU reduced harmonised labelling text can now be prepared on a voluntary basis within new DC/MR procedures, within line extensions, and using MR Art. 61.3 procedures.
- The cover letter template for new applications in MRP/DCP and the notification form for Art. 61.3 procedures are also updated to reflect this agreement. Applicants are reminded that the BPG also provides useful general recommendations and examples on how to prepare multilingual packs and links to national guidance.
- The updated BPG has now been published on the CMDh website under “Procedural Guidance > Application for MA”. Here, you can view the track changed (Feb 2024) and clean (July 2024) versions of the guide.
- The updated cover letter template for new applications has now been published under “Templates > Application for MA”. Here, you can view the track changed (Oct 2021)and clean (June 2024) versions of the template.
- The updated template for Art. 61.3 notifications has now been published under “Procedural guidance > Art. 61.3 procedure”. Here, you can view the track changed and clean versions of the form.
2. Template for Requests for MRP/RUP
The CMDh agreed an update of the template for requests for MRP/RUP.
- With the update, the tick boxes on GMP status to be filled in by the applicant have been amended, in line with the process for confirmation of GMP compliance in MRP/RUP (i.e. the RMS should actively (re)assess the validity of the submitted GMP documentation in connection with the preparation of the updated AR). For that purpose, a new section IX on GMP documentation (to be filled in by the RMS) has been included in the document.
- The updated template has now been published on the CMDh website under “Templates > MRP/RUP”.
- Here, you can view the track changed (April 2024) and clean (June 2024) versions of the template
3. Meeting with representatives of Interested Parties
The CMDh convened a meeting with Interested Parties on 27 June 2024.
The topics on the agenda included, amongst others:
- feedback on the CMDh survey with Interested Parties,
- updates from CMDh WGs,
- harmonisation of product information by requesting variation worksharing,
- resources,
- variations and
- revision of the Variation Regulation.
All presentations have now been published on the CMDh website under “About CMDh > Contact with Representative Organisations”. Links to the presentations (except one) are provided below.
- AESGP – Type IB variations in MRP impacting PI – Discussion about the implementation phase
- AESGP – SPOR IDMP – AESGP Position on Variation Classification Guideline – changes needed
- Medicines for Europe – Availability of resources, Variation Regulation, Repurposing
- CMDh – Feedback from Safety Outcome Survey Working Group
- CMDh – Feedback from Multilingual Packaging Working Group
4. Revision of the Variation framework
The CMDh was informed that the proposed amendment to the guidelines on variations
categories and procedures have been published for stakeholder consultation and Interested
Further information is available in this blog post.
- The proposal aims to make the lifecycle management of human medicines more efficient and future-proof.
- Interested Parties are invited to provide their comments by 23 August 2024.
- Rapporteurs of all CMDh guidance documents on variations were requested to prepare a
- proposed update of the guidance in adaptation of the amended variation regulation (Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024) in the next few months to have it ready by 2025.
5. Submission of parallel national variations instead of worksharing
The CMDh discussed a request for variation worksharing instead of parallel national
variations.
- The CMDh agreed that the significant changes applied in relation to the replacement of a drug manufacturing site should be submitted via variation worksharing, for a better use of resources and the implementation of a timely harmonised outcome across the EU.
- The worksharing should include MAs in all MSs where the product is authorised, even if the variation are already in an advanced stage (or have been finalised).
- The CMDh also received a communication from the applicant, noting that the submission of worksharing variation application is not yet mandatory.
- However, the CMDh has strongly recommended the use of variation worksharing for years for the above-mentioned reasons.
- A letter will be sent to the MAH
6. Acceptance of GMP certificates issued by MHRA
Following the May CMDh discussion, the EMA provided further feedback from the GMDP IWG
on the process for use of GMP certificates issued by MHRA for UK and 3rd country
manufacturing sites post-Brexit.
- The CMDh agreed that UK GMP certificates for sites located in the UK can continue to be automatically recognised by the NCAs as these are covered by the EU-UK Trade and Cooperation Agreement (TCA) and they can be verified in the MHRA system.
- However, for sites located in 3rd countries (i.e. outside the UK) it would be for the Supervisory Authorities (GMP inspectors from the NCA of the batch release site) to decide if the UK GMP certificates are acceptable.
- The submission of UK GMP certificates as part of an application for sites located in third countries should only be considered as supportive.
- When such certificates are received, the RMS will contact its national inspectorate, which will in turn contact the relevant Supervisory Authority.
- Applicants are therefore encouraged to submit EU certificates.
- The agreement published in the September 2023 CMDh minutes is superseded by the above.
7. Presence of nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients
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&As 8, 9, 10, 14 and 15 have been updated to clarify the current approach for products
- where nitrosamine impurities can be controlled according to ICH Q3A/B limits.
- In addition, Q&A 10 has been amended to update the timelines for Ames test acceptability and Q&A 16 to clarify the responsibilities of MAHs and API manufacturers when reference is made to ASMFs and CEPs.
- The new Q&As have now been published on the EMA website after adoption by CHMP .
- You can view the updated document (19 July 2024) here.
8. Medical Device Coordination Group (MDCG) Post Market Surveillance and Vigilance
Working Group
The co-chair of the MDCG Post Market Surveillance and Vigilance Working Group informed
the CMDh about the ongoing discussion points and ongoing work within the medical device
regulatory framework regarding the transmission of relevant information between medical
device competent authorities and medicines authorities in circumstances involving drugdevice combination products regulated under the medical device legislation, in which there is
a suspicion that the medicinal substance may have contributed to a serious incident or field
safety corrective action.
- Feedback was requested from the CMDh on how to involve medicines authorities in the above discussions in order to adopt more consistent approaches.
- A call for volunteers (including information on the work of the group and the expected workload) will be launched for MSs to check within their NCAs the interest of those involved in consultations on ancillary medicinal substances to join the group.
9. DCP application in parallel to centralised and decentralised procedures under the same GMA
The CMDh discussed the acceptability of a DCP application when the medicinal product has
already been authorised via centralised and decentralised procedures under the same Global Marketing Authorisation (GMA) i.e. different MAHs belonging to the same group of companies.
- The applicant holds CAP and DCP MAs as a result of the acquisition of other companies, and intends to submit a new DCP for a medicinal product with the same active substance with a new developed formulation (currently under development) and dossier, supported by a new bioequivalence study.
- The applicant informed the RMS that they are planning to withdraw the CAPs when their internal criteria for a withdrawal are fulfilled.
- Reference was made to previous CMDh discussions (see CMDh minutes from May and November 2013 and February 2023).
- The issue will be discussed further once feedback from the EC has been received.
10. Request for extension of clock-stop
The CMDh was informed about a request for extension of the clock-stop beyond 1 year for a
DCP. The applicant will conduct a new bioequivalence study to solve a major objection, raised
at day 70 of the procedure, concerning pharmacokinetics and quality.
- Following a first clockstop extension, the applicant informed of a delay in the submission of study results due to the regional variability in obtaining regulatory approval and requested an additional extension.
- The RMS considered that the justification for extension of the clock-stop is acceptable.
- The CMDh agreed with the RMS position.
11. Guideline on the environmental risk assessment of medicinal products for human use
Sweden reported from a meeting held between EMA and CMDh representatives concerning the implementation of the updated guideline on the environmental risk assessment of medicinal products for human use, which will be applicable as of 1 September 2024.
- The CMDh agreed that applications submitted on or after 1 September 2024 will be required to adhere to the revised ERA guideline. As of 1st September, applications need to include a document in Module 1.6 to pass validation.
- The content of the ERA is subject to assessment during the procedure.
- The CMDh agreed that MAs with an existing Module 1.6 (regardless of the content) do not need to be updated prior to the submission of MRP/RUP.
- MAs without Module 1.6 will continue to have to submit a variation prior to the start of MRP/RUP.
- Even if the variation results in a commitment for an ERA, the MRP/RUP can be initiated before the commitment is fulfilled and the new CMS can issue an MA with this commitment pending.
- It was confirmed that variations for adding/updating an ERA should be classified as Type IB C.I.z.
- If an ERA is added/updated prior to a MRP/RUP together with other updates to th dossier, these updates can be submitted as a single variation Type II C.I.z, as agreed in the CMDh ”Examples for acceptable and not acceptable groupings for MRP/DCP products”.
- The CMDh will further discuss the implementation and consider updating the CMDh AR templates.
12. Generic/hybrid marketing authorisations – Data exclusivity of Art. 10a dossier when generic product is already authorised under the same GMA
Following the discussion in May, Sweden introduced an example of a case where there is no
reference medicinal product available for a generic application and an Art. 10a (well established use (WEU)) application is submitted.
- The application was based on literature from various non-available products that are out of data exclusivity and on results from indirect bridging studies with another Art. 10a product on the EU market but authorised for less than 8 years.
- The EC agreed with CMDh that it would seem contradictory if this would be possible in an Art. 10a application, as a generic application referring to a reference medicinal product authorised for less than 8 years would not be accepted.
- Therefore, reliance on indirect bridging studies with an Art. 10a product will only be possible once it has been authorised for 8 years.
13. Post-approval commitments in RUP
The CMDh discussed the possibility of witholding the marketing of medicinal products
authorised in RUPs with post-approval commitments (PACs). It was noted that sometimes RUPs are finalised with a PAC to update the PI via a variation when a PSRPHs was raised during the procedure, by the new CMSs in relation to the PI.
- It was noted that PSRPHs should be discussed in a referral and all other outstanding issues for the requested variation after the EoP are “other concerns”.
- It is therefore not acceptable to grant the MA only after approval of the variation.
- Furthermore, the MA should always be based on the SmPC from the RUP outcome (same SmPC as in the old CMS).
- The updated SmPC from the variation should not be the basis for issuing the MA.
- Generally, the RMSs will request the MAH to update the PI before submitting the RUP, as needed.
- In line with current CMDh guidelines, the CMDh stressed that, once the EU phase is positively approved, PACs can neither withhold granting a marketing authorisation nor the marketing of a medicinal product once a marketing authorisation has been granted.
- It is also not acceptable to solve a PSRPH with a PAC and these PACs should also not be associated with commitments not to market the product prior to the submission of the variation.
14. Revision history in CMDh documents
Following the May CMDh agreement, the CMDh agreed on the process and template for the
prospective inclusion of a “revision history” in updated CMDh guidance documents adopted
from the June CMDh meeting onwards.
Industry Update webinar on Regulatory Procedure Management for Product Lifecycle Management on IRIS
A webinar with the above title was held on 13 June 2024. It has information on the following:
- Progress and roadmap of Regulatory Procedure Management (RPM) for product Lifecycle Management (PLM) transition to IRIS
- Key actions and impacts on pharmaceutical industries
- Periodic Safety Update Reports
- IRIS Industry portal demo
- Next steps
- Q&A session
You can view it here.
Updated PLM Portal eAF FHIR XML Release notes now available
An updated version of the PLM Portal eAF FHIR XML Release notes reflecting the implementation of FHIR XML 2.0.1 in the PLM Portal eAF (released to production on 28 June 2024) are now available on the PLM Portal and in the section of the PLM Portal eAF, Documentation section, together with several updated documents to provide consumers of the FHIR XML message the easiest possible way to upgrade to the eAF XML 2.0.1 or to start the implementation now with the latest version.
Source: eSubmission
Clinical Trials Coordination Group
The following documents have been updated/introduced:
- 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 5 – June 2024 – Pages 1 and 2 of the document detail the changes in version 5 compared to earlier versions of the document.. - Annex I – Cover letter template
Annex to the Best Practice Guide for sponsors of multinational clinical trials with different protocol versions approved in different Member States under the Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014
Version 5 – June 2024 – Page 1 of the document details the changes in Version 5 compared to earlier versions of the document. - Annex II – Fees for transitional trials in MSs
Version 1 – June 2024
Source: HMA