CMDh and other EU updates – September 2024

Last updated: 22 October 2024

DateUpdate(s)
22 Oct 2024With reference to section Report from the CMDh meeting held on 17-18 September 2024
i) The section heading was updated to Report and minutes from the CMDh meeting held on 17-18 September 2024.
ii) A link was added to minutes from the meeting.
iii) A second paragraph wad added to Item 1 in this section.
iv) New items 6, 7 and and 8 were added.
30 Sep 2024New section Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle added.
27 Sep 2024Links are now provided to updated documents under section Report from the CMDh meeting held on 17-18 September 2024, sub-sections 1,4 and 5
26 Sep 2024New section Report from the CMDh meeting held on 17-18 September 2024 added.
24 Sep 2024Addition of new section Labelling requirements for metered dose inhalers containing fluorinated greenhouse gases .
19 Sept 2024New section Public System Demo Q3/2024 – EMA webinar added.
13 Sept 2024Added new section PRIME eligibility requests 2025- Deadlines for submission and timetable for assessment
Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle

This reflection paper provides considerations on the use of AI/ML in the lifecycle of medicinal products, including medicinal products development, authorisation, and post-authorisation.

Given the rapid development in this field, the aim of this reflection paper is to reflect on the principles that are relevant for regulatory evaluation when these emerging technologies are applied to support safe and effective development, manufacturing and use of medicines.

The final version of this paper was adopted by the CHMP on 9 September 2024.

Source: EMA


Overview of of timeables CMDh 60-day procedures for MRP/DCP 2024/2025

The following overviews of timetables have been published:

These documents were produced by the CMDh as guidance to inform Applicants of the possible timetables for the applications referred to the CMDh, in accordance with Article 29(1) of Directive 2001/83/EC, as amended and Article13 of Regulation (EC) No 1234/2008.

The starting date for the 60 days procedure should in principle be no later than 30 days after Day 90 or Day 210 of the Mutual Recognition or Decentralised Procedures, respectively, or the final day of the Variation procedure. However, due to the calendars of CMDh meetings, it might not be possible to comply with the 30-day rule in all situations.


Report and minutes from the CMDh meeting held on 17-18 September 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. Guideline on the Environmental Risk Assessment (ERA) and mutual recognition/repeat-use procedures

The CMDh agreed an update of the request form for MRP/RUP.

  • To facilitate the implementation of the updated ERA guideline, applicants are requested to confirm before the start of an MRP/RUP that the ERA provided in Module 1.6 is in line with the current version of the guideline.
  • For MRP/RUP requests submitted until 31 March 2025, it is possible 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 is not in line with the current version of the Guideline.
  • The updated template has now been published on the CMDh website under “Templates > MRP/RUP”
  • Here, you can view the tracked changed (June 2024) and clean (September 2024) versions of the template.

The CMDh also discussed how to handle duplicates of procedures submitted after 1
September 2024 that follow the same timelines as the original MAA, when the original
procedure was submitted before 1 September 2024.

  • The CMDh agreed that in such cases it would be acceptable to validate the duplicate procedures according to common practice as before 1 September 2024, as they follow for the original MAA.
  • As these duplicates could have different CMSs as the original MAA, it would be up to the new CMS to accept to be added to the procedure or not.
  • The above does not apply to duplicate procedures that are submitted when the original MAA has already been finalised.

2. Revision of Acceptable Intake (AI) for N-nitroso-sertraline

On 1 September 2024, an update of Appendix I of the EMA/CMDh Q&A on nitrosamines was published, including among other things, a revision of the established Acceptable Intake (AI) for N-nitrososertraline from 1500 ng/day to 100 ng/day.

Marketing authorisation holders of sertraline containing medicinal products are requested to assess the impact of the reduced AI on their products and (re-)submit their step 2 response to (re-)confirm under which scenario their products should be classified under the newly published AI.

3. Submission of Certificate of the European Pharmacopoeia (CEP) variations

In June 2024 the CMDh agreed a pragmatic approach to the update of CEPs for hydrochlorothiazide (HCTZ) concerning the inclusion and subsequent removal of the impurity N-nitrosohydrochlorothiazide.

The CMDh now agreed that the same approach can also be taken for other CEPs, where the same situation applies (when a nitrosamine limit was first added to the CEP and subsequently removed following classification of the nitrosamine as non-mutagenic impurity):

  • MAs containing approved revision of CEP before the inclusion of the nitrosamine impurity:
    • The variation guideline suggest two type IB variations (category B.III.1.a.2) as condition no.2 is not fulfilled: one for the addition of the impurity and another for its deletion.
    • The CMDh has agreed that the version of the CEP with the added impurity can be skipped and only a single type IA variation for the CEP revision where the nitrosamine impurity has been removed needs to be submitted.
    • The reason for skipping the CEP revision which contains the nitrosamine impurity is based on common recommendation, that it is allowed to skip the immediate
      implementation and the variation submission, if a CEP revision is not a consequence of a quality and/or safety issue.
    • Additionally, the condition 2, in this specific situation, can be regarded as fulfilled, since at the end, there is no change in the specifications for impurities.
  • MAs containing the approved revision of CEP with included nitrosamine impurity:
    • The variation guideline mandates a type IB variation for the registration of the latest version of the CEP.
    • However, the CMDh has agreed that a type IA variation can be submitted in this specific case, as it has been confirmed that the impurity is non-mutagenic and unnecessary for inclusion in the CEP.

However, MAHs are reminded to keep their dossiers up to date and should not delay the implementation of CEP updates.

4. Q&A on Pharmacovigilance

The CMDh has agreed an update of the Questions and Answers on Pharmacovigilance Legislation.

  • The Answer to Question 8 has been replaced by a reference to the Q&A 3.3 on variations which provides guidance on the variations to implement PI updates following PSUSAs.
  • Question 10 has been revised to provide updated guidance on the extrapolation of the outcome of PSUSA to other products that were not within the scope of the single assessment (other fixed combinations/mono products) and for drug-drug interactions.
  • The updated document has now been published on the CMDh website under “Questions and Answers”.
  • Here, you can view the track changed (March 2024) and clean (September 2024) versions of the document.

5. Timetables for MRP/DCP applications referred to the CMDh in accordance with Article 29(1) of Directive 2001/83/EC

The CMDh has adopted an updated guidance document with the timetables for MRP/DCP applications referred to the CMDh for the 60-days referral procedure in 2025.

The updated guidance document has now been published on the CMDh website under “CMDh referrals”.

Here, you can view the Overview of timetables 2025 CMDh 60-day procedures for MRP/DCP applications.

6. Working Party on Variation Regulation

The WP Chair reported from the September 2024 meeting.

  • The WP Chair presented an overview of the comments received following the stakeholder consultation on the proposed amendments to the EC guidelines on variations categories and procedures.
  • The WP discussed updates to several guidance documents, Q&As and templates related to variations to align them with the amended Variation Regulation (which will be applicable from 1 January 2025). The agreed changes were presented to the CMDh for adoption.
  • The CMDh discussed and agreed the update of 16 guidance documents and templates related to variations to bring them in line with the amended Variations Regulation, applicable from January 2025.
  • The documents have been prepared and pre-discussed in the Variation Regulation Working Party.
  • Minor amendments to some of the documents were agreed in the CMDh.
  • Once a more mature draft of the Variations Guidelines will be available, further amendments of the CMDh documents might be needed.
  • The updated guidance documents and templates should be published in advance of the applicability of the amended Variations Regulation, although the updated guidance/templates will also only apply from 1 January 2025.

7. 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 changes to update the product information according to the Company Core Data Sheet (CCDS) 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 variations are already in an advanced stage (or have been finalised).
  • It was noted that the MAH was already requested in 2023 to harmonise the product information via variation worksharing.
  • The MAH will be reminded of the previous communication.
  • A letter will be sent to the MAH.

The CMDh was informed about parallel national variation submissions by the MAH to
harmonise the texts to the company internal safety framework.

  • Following requests to resubmit the variations via worksharing procedure, the MAH argued that different formulations are authorised in the MSs, which might need product specific assessment.
  • Although a worksharing procedure would have been preferable, the CMDh agreed that in this specific case no re-submission via variation worksharing will be requested by the CMDh.
  • MSs were asked to share their Assessment Reports (ARs).

8. Mobile scanning technologies included in labelling and PL

The CMDh discussed if it would be acceptable for a mobile technology feature (e.g. QR code)
on the package and/or in the PL to link to statutory information located on a platform created
and operated by a third party provided that the platform fulfils other conditions of the
guideline (no commercial elements, no external links etc.).

  • Positions for and against the approach were expressed.
  • In a trend vote, a majority of the CMDh was in favour of allowing platforms created and operated by a third party as long as the MAH remains fully responsible for its content.
  • However, before a final decision is taken, it was agreed to await the ongoing discussion on the revision of the related QRD guidance for Centrally Authorised Products (CAPs).

Labelling requirements for metered dose inhalers containing fluorinated greenhouse gases 

Guidance is now available for MAHs of centrally authorised metered dose inhalers (MDIs) that use fluorinated greenhouse gases (F-gases) as propellants.

This is in line with Regulation (EU) 2024/573, which introduces new labelling requirements for MDIs with F-gases starting 1 January 2025. It is part of EU efforts to reduce F-gas emissions. 

This guidance provides answers to key questions such as:

  • How the regulation impacts MDIs with F-gases
  • How to label these products
  • Which regulatory procedure should be used to comply with the new requirements

Quality review of document (QRD) statements are also available in a separate document containing translations into all the official EU / EEA languages.

EMA published these documents in September 2024.

Source: EMA


Public System Demo Q3/2024 – EMA webinar

You can view the entire webinar here or view it by section by clicking on the time stamps below:

European Shortages Monitoring Platform (ESMP) 0:05:30

EMA Account Management – Authentication to EMA systems using email address 1:06:35

New Fee Regulation (NFR) 1:21:30

Union Product Database (UPD) 1:50:00

Product Management Services (PMS) 2:10:25

Product User Interface (PUI) 2:30:10

Electronic Product Information (ePI) 3:00:00

Regulatory Procedure Management (RPM) for PLM 3:20:40

Electronic Application Form (eAF) 3:50:15


PRIME eligibility requests 2025- Deadlines for submission and timetable for assessment

PRIME is a scheme run by the EMA to enhance support for the development of medicines that target an unmet medical need.

This voluntary scheme is based on enhanced interaction and early dialogue with developers of promising medicines, to optimise development plans and speed up evaluation so these medicines can reach patients earlier.

You can view the updated timetable of 10 September 202 here.

Further information on PRIME is available here.

Source: EMA


Start of non-CAPs data load on PMS Product UI

EMA has confirmed that that non-Centrally Authorised Products* (non-CAP) data are currently being loaded in read-only mode on the Product Management Service (PMS) Product User Interface (PUI), live on the live on the Product Lifecycle Management (PLM) Portal.

  • This data load is expected to be completed by the end of September 2024, after which all non-CAP data will be available in read-only mode on the PUI.
  • Please note, this data load will not yet trigger the availability of non-CAPs in the web-based electronic Application Form (eAF).
  • Following the deployment of further performance improvements, non-CAPs will become available also in the eAF.
  • During the non-CAP data load, users of the PLM Portal and IRIS Industry & Network Portal may experience minor performance issues, such as slower system responses.
  • In such circumstances, users do not need to raise this via EMA Service Desk.

IMPORTANT: To avoid platform overload and preserve the performance of the PLM platform while the data load is ongoing, the EMA requests that National Competent Authorities (NCAs) refrain from requesting PMS roles at this time. Current PLM PUI and eAF users are also strongly encouraged to minimise activity on the PLM Portal

*Products authorised throughout mutual recognition procedure (MRP), decentralised procedure (DCP) and national procedure (NAP).

Source: eSubmission