Last updated: 27 July 2023
See updates at the end of the post.
Draft Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle
This reflection paper provides considerations on the use of AI and Machine Learning 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 scientific principles that are relevant for regulatory evaluation when these emerging technologies are applied to support safe and effective development and use of medicines.
You can understand the basics of AI and machine learning in this post.
Guidance document on voting in the framework of discussion and adoption of committee opinions
Revision 2 of the document dated 14 June 2023 is now available. You can view it here.
This document provides guidance on the use of voting in the framework of discussion and adoption of opinions by the EMAꞌs scientific committees and by the Co-ordination groups for Mutual recognition and Decentralised procedures.
Source: EMA
Minutes of CMDh meeting (of 31 May) with representatives of Interested Parties
You can read the draft minutes of the meeting here. A range of topics were discussed, including the following:
1. Multilingual Labelling in MRP/DCP
Ireland gave an update from the Multilingual Packaging WG including an update of the pilot on preparation of EU reduced harmonised text. Several reminders regarding multilingual packaging were highlighted to Interested Parties in order to smoothen the procedure.
2. Renewal improvements
- Sweden presented the CMDh agreement on a new process for renewals as of March 2023.
- The previous shortened renewal with reduced documentation for generic MAs is now the standard process for all legal bases. MSs still have the possibility to request additional information if this is needed due to national legislation.
- It was stressed that requesting full documentation is still possible, if needed according to
- national legislation. This does, however, not mean that the extended timeline has to be used
- It was also noted that the new process has only recently been introduced and there is a transition time in which already started procedures can be finalised according to the old process.
- The CMDh will consider providing a list of MSs that still require full documentation according to their national legislation. Interested Parties were encouraged to monitor the situation and to inform in case there are problems with the new process.
3. Availability of updated PI following safety reviews
The Czech Republic gave an update on the activities of the SOS WG (Safety Outcome Survey Working Group). The aim of the work is to make safety information better accessible/visible for companies (and assessors) to implement. A dedicated meeting with representatives of Interested Parties on topic I&II (publishing the outcomes of safety variations) is foreseen in the future.
- An overview was presented on how MSs make updated PI publicly available following safety reviews. It was acknowledged that there is room for improvement by MSs on updating Public Assessment Reports (PARs) and uploading updated PI in CTS (and therefore in the MRI product Index).
- The outcome of variaation worksharing procedures should also be made available
- It was also stressed that the information is scattered across different locations e.g EMA, CMDh and the European Commission website and it was suggested that ‘instructions for use’ are provided to guide MAHs and assessors
Source: CMDh
Minutes of CMDh meeting (of 16 May) with Interested Parties, on variations
This was a brainstorming meeting to exchange views on a future revision of the Variation Regulation. The meeting has been requested by a trade association.
The main themes brought forward by Interested Parties concerned the implementation of ICH Q12 Technical and regulatory considerations for pharmaceutical product lifecycle management – Scientific guideline, digitalisation and simplification. These points are also supported by the CMDh. Questions on the update of the variations framework will be addressed to the EC and the feedback will be shared with Interested Parties.
The participants were informed that the submitted proposals were already briefly discussed
in the Working Party on Variation Regulation. They will be further considered by the CMDh and EMA, as needed. Any questions on procedural aspects with regard to an update of the legislation need to be addressed to the EC.
You can view the minutes of the meeting here, and presentations from the interested parties at the links below:
AESGP
EFPIA
EUCOPE
Medicines for Europe
Source: CMDh
Guidance for the transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation
This Guidance reflects the agreement reached by CTAG Contact Points and
supersedes the chapter 11 of the Q&A on the application of the CTR (version 6.4).
Source: European Commission
Compilation of Union Procedures on Inspections and Exchange of Information
Rev 19 (June 2023) of the above compilation has been published and you can view it here.
PRIME eligibility requests
You can view the 2024 PRIME deadlines for submission and timetable for assessment here.
Instrument for Pre-Accession Assistance (IPA) Advanced EMA training on Quality and inspections
The EMA recently held a series of seven seminars under the main heading, Instrument for Pre-Accession Assistance (IPA) Advanced EMA training on Quality and inspections, which may be of interest to a wider audience. Links are provided below to six of the seven seminars.
Source: EMA
Guidance on Parallel EMA/HTA body (HTAb) Scientific Advice for the Interim Period
This guidance highlights ideal timelines and actions for each party undertaking a Parallel EMA/HTAb Scientific Advice.
This is a multi-stakeholder procedure with EMA and HTAbs being equal partners. As a multi-stakeholder procedure, collaboration and communication between all stakeholders are important to ensure agreement and clarity on the ownership of different actions, and to deliver on the objectives of the exercise.
This parallel EMA/HTA body Scientific Advice for the interim period is provided solely on the initiative of individual HTA agencies in preparation for the application from 12 January 2025 of Regulation (EU) 2021/2282 on health technology assessment.
Source: EMA
Report and minutes from the CMDh meeting held on 20-21 June 2023
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) Request for RMS in a decentralised procedure for medicinal products for human use
The CMDh agreed an update of the RMS request form in DCP.
- The form has been reviewed with the experience gained, based on proposals for improvement discussed in the CMDh presidency meeting in Sweden.
- The use of the form will become mandatory as of 1 September 2023 for all upcoming requests, but it can be used before that date on a voluntary basis.
- Requests submitted before 1 September 2023 do not have to be updated to the new form.
- The updated document has now been published on the CMDh website under “Templates > Application for MA”. You can download it here.
2) CMDh SOP on decision-making process for new active substance status or extension of marketing protection or data exclusivity
The CMDh agreed an update of its SOP on decision-making process for new active substance status or extension of marketing protection or data exclusivity.
- Information on the interpretation of the term “new indication” in the framework of granting an additional year of data exclusivity according to Art. 10(5) of Directive 2001/83/EC, has been included in the guidance.
- The updated document has now been published on the CMDh website under “Procedural Guidance > Application for MA”. Here, you can view the track changed (October 2017) and clean (June 2023) versions of the document.
3) CMDh/EMA Working Party (WP) on Paediatric Regulation
The CMDh has agreed an update of its Best Practice Guide on Article 45 and 46 – Paediatric Worksharing Procedures as well as an update of the Questions and Answers on the Paediatric Regulation.
- BPG on Article 45 and 46 -Paediatric Worksharing Procedures
- Clarification has been included in the guidance that the need to start an Art. 46 worksharing procedure should be discussed with the rapporteur, in case the same study will also be submitted as a variation. A discussion in the WP or CMDh are not needed.
- It has further been clarified that procedures for which a restriction of use is considered warranted should be brought for discussion in the WP on Paediatric Regulation and CMDh during the procedure.
- The updated BPG has now been published on the CMDh website under “Paediatric Regulation > Guidance documents”. Here you can view the track changed (July 2022) and clean (June 2023) versions of the document.
- Questions and Answers on the Paediatric Regulation
- The CMDh also agreed an update of the Questions and Answers on the Paediatric Regulation. Q23 on the applicability of Art. 7 and 8 of the Paediatric Regulation to informed consent applications has been aligned with the relevant Q&A published by the EMA.
- The updated Q&A document has now been be published on the CMDh website under “Questions & Answers”. Here, you can view the track changed (september 2021) and clean (June 2023) versions of the document.
4) CMDh requests for variation worksharing
- Following the introduction in May and the analysis of cases where the CMDh requested MAHs to submit variations as worksharing procedures instead of parallel national variations, the CMDh agreed that the exercise is useful for the network and the CMDh should continue to send these requests when they are identified.
- The CMDh also considered that it would be useful to have a systematic check if the submission has been changed into a variation worksharing procedure (e.g. 6 months after the request).
- MSs were asked to provide ideas on how to make the process more efficient.
- A question will be circulated on how MSs identify such cases and how they take a decision to bring it to the CMDh.
- A proposal will be prepared on how to agree on and implement harmonised PI wording
- A topic will be prepared for discussion in the next meeting of the Working Party on Variation Regulation on negative experiences gathered in worksharing procedures in order to improve the guidance, as needed.
5) User testing of the package leaflet
- The EMA informed the CMDh about the outcome of the QRD discussions on the possibility of virtual/remote user testing of the package leaflet.
- QRD agreed that in-person user testing remains the preferred option. However, also virtual/remote user testing can still be allowed.
- Due to the current legal framework, it was however stressed that a printed version of the package leaflet has to be used during the interview namely to address aspects as the design, layout, quality of paper etc.
6) Blister packs with empty cavities – risk for potential medication errors / patient non-compliance / EMA
- The CMDh was updated on the discussion in the QRD group on the risk for potential medication errors / patient non-compliance due to blister packs with empty cavities.
- The issue was previously discussed in QRD where QRD agreed with the CMDh concerns associated with the empty cavities and intended to update their stylistic matters guidance to recommend that empty cavities should be avoided and to provide further specific guidance in case it cannot be avoided.
- During a QRD meeting with Interested Parties meeting, trade associations stressed that such cases would be exceptional and further specific guidance would increase the manufacturing complexity and could potentially lead to supply issues.
- It also seemed that the issues are restricted to some MSs and some MAHs. The QRD therefore considered that specific guidance could be confusing to MAHs and consulted CMDh if a simple general guidance and/or recommendation to avoid empty blisters would suffice.
- The CMDh asked EMA to share the feedback from Interested Parties. A proposal for a general wording to be included in the guidance will be shared with CMDh
7) Orphan similarity assessment
- The CMDh discussed the orphan similarity assessment based on a recently submitted generic application.
- The active substance and the mechanism of action of the generic product are the same as an authorised orphan medicinal product and there seems to be an overlap for a part of the indication.
- Based on the questions raised, the CMDh advised that the existence of an orphan medicinal product does not automatically block the granting of generic MAs with the same active substance provided that new application is considered non-similar to the authorised orphan medicinal product (e.g. based on a different therapeutic indication) or, if similar, that one of the derogations provided for in Article 8(3) of the Orphan Regulation (EC) No 141/1200 claimed by the applicant applies.
Updates
| Date | Update(s) |
|---|---|
| 27 Jul 2023 | 1) Heading Report from the CMDh meeting held on 20-21 June 2023 updated to Report and minutes from the CMDh meeting held on 20-21 June 2023. 2) Link added to minutes from the meeting. 3) Items 4, 5, 6 and 7 added under the updated heading. |
| 26 Jul 2023 | Link provided to the updated document Guidance document on voting in the framework of discussion and adoption of committee opinions |
| 21 Jul 2023 | The following new headings and relevant content were added: 1) Minutes of CMDh meeting (of 31 May) with representatives of Interested Parties 2) Minutes of CMDh meeting (of 16 May) with Interested Parties, on variations |
| 19 Jul 2023 | New section added entitled Guidance for the transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation. |
| 14 July 2023 | Information added on the following: 1) PRIME eligibility requests timetable. 2) Update to Compilation of Union Procedures on Inspections and Exchange of Information. |
| 13 July 2023 | New heading Instrument for Pre-Accession Assistance (IPA) Advanced EMA training on Quality and inspections added, with links to seminars. |