Last updated: 28 November 2022
See updates at the end of this post.
Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of RMPs (main body and annexes 4 and 6)
EMA has published the above guidance. It gives general guidance to companies on the retention/removal of Protected Personal Data (PPD) and identification of Commercially Confidential Information (CCI). All the changes suggested in the guidance are of editorial nature and should be implemented in the RMP during the scientific review process prior to the Opinion and adoption of the final RMP version
Source: EMA
Report and minutes from the CMDh meeting held on 11-13 October 2022
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 includes the following items:
1. Q&As on the monitoring of bioequivalence trials
The CMDh, in liaison with the GCP Inspectors Working Group, agreed Q&As to give guidance to applicants on the monitoring of bioequivalence clinical trials. You can view them here.
2. Call for review for chemically synthesised and biological medicinal products regarding nitrosamine impurities
The CMDh and the EMA agreed an update of the joint 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 has been updated to add the agreed limit for N-nitrosoduloxetine and a new Q&A (Q&A 21) has been added on the approach to control the presence of nitrosamines, while the acceptable intake (AI) is being established.
The updated Q&A of 10 October 2022 has been published on the EMA website. A link is provided from the CMDh website under “Advice from CMDh > Nitrosamine impurities”. You can view it here.
3. Regulation (EC) No 1234/2008 on variations inc. update to Best Practice Guide for the Submission and Processing of Variations in MRP
The CMDh agreed to update of the Best Practice Guide for the handling of type II variations in MRP (Chapter 5 of the BPGs ).
- Guidance on the use of the template for MAH’s responses during type II variations, as agreed in September 2022, has been included in the document.
- The document has also been updated with other changes to reflect the current way of working.
The updated document has been published on the CMDh website under “Procedural Guidance >Variations”. Here, you can view the clean and track changed versions of the guide.
4. Recommendations on submission dates for applicants of the DCP and MRP
The CMDh adopted updated guidance documents with the timetables for MRP/DCP applications to be submitted in 2023. The updated guidance documents has been published on the CMDh website under “Procedural guidance > Application for MA > MRP/DCP”. You can view it here.
5. CMDh Guidance on the Informal Work-Sharing procedure for follow-up for PSUSA for NAPs
The CMDh agreed an update of its guidance on the informal worksharing procedure for follow-up for PSUSA for NAPs (PSUFU). The CMDh agreed that in the very specific and exceptional situation where the MAH anticipates not being able to meet the required submission deadline and applies for an extension, the LMS/Reference Authority/RMS does no longer need to consult the Pharmacovigilance WSP WP, but can bring the request directly to the CMDh for discussion. The updated document has been published on the CMDh website under “Pharmacovigilance > PSUR”
The document has been updated from the version of February 2021 to the version of October 2022. Whilst the track changes to Table of Contents might appear to suggest significant changes to the document, it does not appear to have undergone any significant changes
Here you can view the clean and track changed documents.
6. CMDh Best Practice Guide for handling of Type II variations in MRP
The CMDh agreed to update of the Best Practice Guide for the handling of type II variations in MRP (Chapter 5 of the BPGs for the Submission and Processing of Variations in MRP).
- Guidance on the use of the template for MAH’s responses during type II variations, as agreed in September 2022, has been included in the document.
- The document has also been updated with other changes to reflect the current way of working.
- The CMDh agreed that the dispatch list does not need to be provided anymore as all applications are now submitted via CESP.
The updated document (October 2022) has been published on the CMDh website. Here, you can view the clean and track changed versions. there are track changes throughout the document, so it is well worth reading to learn about and understand all of the changes.
7. Submission of parallel national variations instead of worksharing
The CMDh was made aware of parallel national variations instead of using the variation worksharing procedure. The CMDh agreed that in order to save resources and to achieve and maintain harmonisation of the product information across MSs the MAH should be asked to withdraw the national variations and to re-submit using variation worksharing. Where comments have been made on the previously submitted national variations, these should be taken into account in the resubmission as worksharing. A letter from the CMDh will be sent to the MAH.
8. Renewal submission and MA validity
The CMDh discussed national practices with regard to MA validity when a renewal has been submitted on time but due to procedural reasons has not been started/finalised in time. Most MSs informed the CMDh that in case the renewal has been submitted on time, the national legislation allows them to keep the MA valid even if the renewal has not been finalised in time. However, it was also noted that this is a national issue that is dependent on national legislation and outside of the scope of the CMDh.
Similarly, in the opposite case, where renewals are submitted less than 9 months before the renewal date, most MSs do not accept the submission anymore and the MA will cease to be valid at the time of the renewal. In the same way, this is a national issue and dependent on national legislation.
9. Prescription status issues and referrals to the CMDh
The CMDh discussed questions related to the prescription status of products and under which circumstances they would trigger a referral to the CMDh under Art. 29(1).
It was agreed that if a CMS is withdrawn during an ongoing MAA (in the second phase, i.e. assessment step II in case of a DCP) due to disagreement with the prescription status, this should not automatically trigger a referral to the CMDh at the end of the procedure.
It was noted that the legal status is a national decision and as such cannot be the basis of a potential serious risk to public health (PSRPH) on which an Art. 29 referral is based. Some MSs stated that in case they cannot agree with a proposed OTC status, they would finalise the procedure with prescription-only status. Others considered that a referral based on safety concerns (e.g. linked to the aRMMs) should be possible as the benefit-risk profile of a product is being assessed in the framework of its legal status. It was generally noted that the RMS should not validate a PSRPH raised by a CMS. In case a CMS requests an Art. 29 referral based on a PSRPH, the procedure should be referred to the CMDh, where a discussion on the referral can take place (see also Q&As on CMDh referrals, Q3).
It was agreed that the question should be further discussed in the TF on non-prescription medicinal products, based on a practical example.
10. Different composition of generic medicinal product to be marketed than was used in the BE study
The CMDh discussed if a generic MAA could be acceptable if there are (slight) differences in the composition of the product used in the BE study compared to the product to be marketed, e.g. because the product has been further developed since the BE study has been conducted.
- The CMDh agreed that no general answer can be given and a case-by-case decision needs to be made.
- It needs to be justified why the composition has been changed and assessed what impact this could have on the bioavailability.
- Generally, the product used in the BE study should be representative of the product to be marketed. Minor changes in the composition can be acceptable in case they do not affect the bioavailability.
- The BE study also needs to fulfil the current requirements.
11. Legal basis of a fixed dose combination with different strength than the Reference Medicinal Product (RefMP)
The CMDh discussed if a hybrid application for a fixed-dose combination (FDC) medicinal product (with different strength than the RefMP) could be supported by bioequivalence studies vs. the mono-components (instead of the RefMP). Reference was made to a letter received from the EC in 2017, where it was stated that a hybrid application can only refer to one global marketing authorisation (GMA). As the monocomponents and the FDC form separate GMAs, such a reference would therefore not be possible under Art. 10(3).
Web-based Human Variations electronic Application form (eAF) go-live details
EMA is pleased to inform that the web-based Human Variations electronic application form (eAF) for CAPs – often referred to by its former project name: DADI – will be available for use on 4 November 2022 on the new Product Lifecycle Management (PLM) Portal. EMA has been collaborating with the UNICOM consortium to develop the new web-form.
- Following the release, users of the Human Variations eAF should expect continual work on improvements in the form of regular releases.
- These will be a mix of scheduled improvements, improvements based on user acceptance testing (UAT) feedback or that may be identified by users after the release and new features, such as additional structured data fields.
- Going live as scheduled and continually improving the form is the most effective route to having a high performing web-form in the shortest timeframe and it is in accordance with an Agile way of work
Reminder: This release will not trigger a transition period towards mandatory use. The formal transition period will start after the anticipated March 2023 release when nationally authorised products (NAPs) features will be also added to the form. The interactive PDF eAF will remain available until the end of the transition period. More information is available on the DADI project in this blog post.
Source: Europa
European Medicines Agency Guidance for Applicants seeking scientific advice and protocol assistance
This guidance has been updated from Rev 13. of March 2022 to Rev. 14 of October 2022.
There are substantial changes throughout the document starting with a complete update to the Table of Contents.
Here, you can view the clean and track changed versions.
CHMP protocol assistance scientific advice briefing document template
This document has been updated to Rev.2 of 14 October 2022 and you can download it here.
Source: European Medicines Agency
Updated version of the eAF v1.26.0.0 (human variation) now available
An updated (on 14.10.22) version 1.26.0.0 of the human variation eAFs is now available here. A single change has been implemented to emphasize the mandatory use of OMS for centralised procedure by updating the Declaration label in the Proposed section. There is a very limited impact to users of the forms. The use of the v1.26.0.0 is mandatory since 1st January 2022 (human).
Source: Europa
Updates:
Date | Update |
---|---|
28 Nov 2022 | The following updates were made to this post: 1) The heading Report from the CMDh meeting held on 11-13 October 2022 was updated to Report and minutes from the CMDh meeting held on 11-13 October 2022 and a link to the minutes added under the heading. 2) The content under the sub-heading Recommendations on submission dates for applicants of the DCP and MRP was updated to include a link to the document. 3) Items 6 – 11 wereadded under the heading Report and minutes from the CMDh meeting held on 11-13 October 2022 . |
5 Nov 2022 | Addition of information and link to guidance on Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of RMPs (main body and annexes 4 and 6) |
28 Oct 2022 | Addition of item 5 under the heading Report from the CMDh meeting held on 11-13 October 2022. |
26 Oct 2022 | Item 3 under the heading Report from the CMDh meeting held on 11-13 October 2022 updated to include a link to the updated BPG guide 5 on Submission and Processing of Variations in MRP. |
21 Oct 2022 | New section added entitled Report from the CMDh meeting held on 11-13 October 2022. |