Last updated: 20 December 2022
See updates at the end of this post.
Report and minutes from the CMDh meeting held on 8-10 November 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/or minutes from the above meeting include the following items:
1) Call for review for chemically synthesised and biological medicinal products regarding nitrosamine impurities
The CMDh and the EMA agreed an update of the “Step 2 – Nitrosamine detected response template” considering the newly published Q.21 of the EMA/CMDh Q&A on nitrosamines and to emphasise the need for adherence to published AI limits for known nitrosamines.
A link to the updated template is also available elsewhere on this page.
2) HaRP (Harmonisation of RMP Project) Assessment Report Template
The CMDh agreed a new version of the HaRP assessment report template. The template has been updated and improved based on the experience gained since the beginning of the project and based on questions raised on how the assessment is performed.
The updated template has been published on the CMDh website under “Templates > RMP”.
3) Meeting with representatives of Interested Parties
The CMDh convened a meeting with Interested Parties in the margins of the November CMDh plenary meeting. The topics discussed included, amongst others:
- multilingual labelling,
- resources, repeat-use procedures,
- availability of updated PI following safety reviews and
- nitrosamines.
All presentations have been published on the CMDh website under “About CMDh > Contact with Representative Organisations > Meeting with interested parties – 9 November 2022″ You can view them here.
4) Information on overdose in Section 4.9 of the SmPC
As a follow-up of the discussion in November 2021, Finland (FI) informed the CMDh that the topic on overdose information in section 4.9 of the SmPC has been further discussed with the DARWIN group and with the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). DARWIN has looked into the possibility of conducting a study on the subject, but in view of the limitations, this is currently not possible. Information has also been received from the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) that a new position statement from this group on activated charcoal is about to be published. FI proposed to work on a guidance document on which information on the treatment of overdose should be included in section 4.9 of the SmPC.
The importance of having the correct information on the treatment of overdose in section 4.9 was acknowledged. However, it was considered that guidance on a specific section of the SmPC would be outside of the remit of the CMDh and other groups should be in the lead. It was further noted that the SmPC Guideline gives already information on section 4.9, but companies seem to be reluctant to update the information. The need to keep the product information up-to-date (including section 4.9) was stressed again to trade associations in the IP meeting held in the margins of the November CMDh meeting.
5) Reflection paper on criteria to be considered for the evaluation of new active substance (NAS) status of biological substances
The draft reflection paper on criteria to be considered for the evaluation of new active substance (NAS) status of biological substances as adopted by CHMP was presented to the CMDh for information. The document has been published for six months of public consultation.
6) Annex to the Guideline on Excipients in the labelling and package leaflet of medicinal products for human use
The CMDh discussed a proposal to ask NcWP/the Excipients Drafting Group to include benzyl alcohol (administered orally) in a list of excipients to be re-considered.
The CMDh was informed that some oral flavoured antibiotic preparations contain concentrations of benzyl alcohol of less than 1 ppm. There is no threshold in the recommendations of the excipients guideline and inclusion of the warnings as per the current guideline might lead to therapeutic failure.
The CMDh agreed to forward the request to CHMP (NcWP).
7) Legal basis – 10(1) vs 10(3) of Directive 2001/83/EC
i) Product for injection and/or infusion
The CMDh discussed if an abridged application, submitted as solution for injection for the lowest strength and solution for infusion for the higher strengths, could be validated under Art. 10(1) generic application, when the RefMP is authorised as solution for injection/infusion for all strengths, or if the applicant should consider submitting the application under e.g. Art. 10(3) hybrid application in this case.
From the SmPC information of the RefMP, it can be ascertained that the lowest strength of the RefMP is intended for injection, while the other strengths are intended for infusion, as proposed in the abridged application.
The CMDh agreed that in this situation the RMS could check the SmPC of the RefMP at the validation stage and, based on this information, the MAA could be accepted under Art. 10(1).
ii) Product for infusion without solvent
The CMDh discussed if an abridged application, applied for as powder and solvent for solution for infusion (including solvent), could be validated under Art. 10(1) generic application, if the RefMP is authorised as powder for solution for injection/infusion (without solvent), or if the applicant should consider submitting the application under e.g. Art. 10(3) hybrid application.
There was no harmonised view among MSs on the most appropriate approach. Some MSs would accept the application under Art. 10(1) based on the fact that the pharmaceutical form at the time of administration is the same and with the same concentration. Others consider that an Art. 10(3) application would be appropriate in this case, as the fact to have a solvent included or not would lead to differences in the pharmaceutical form and to differences in the wording of the SmPC of the product applied for and the RefMP. It was suggested that the RMS should take a decision and justify it based on their considerations.
8. Presence of nitrosamine impurities in human medicinal products containing
chemically synthesised active pharmaceutical ingredients
Denmark proposed that in case new nitrosamines have been detected after the EoP and some MSs have already issued the MA, but others have not, the MA should be issued in all MSs and confirmatory testing does not have to be provided before the MA can be granted. According to the EMA/CMDh Q&A No. 5 the MAH is obliged to maintain the quality of his product throughout its lifecycle and to consider newly identified risk factors and limits for nitrosamines. The CMDh agreed with the proposal. It was agreed that no specific reminder to the MAH of their obligation to monitor the quality of their product is needed.
9. Availability of updated PI following safety reviews
As a follow-up to the discussion with trade associations on their project on “reference safety information”, CZ presented an overview of how MSs make updated PI following safety reviews publicly available. It was acknowledged that there is room for improvement by MSs on updating PARs and uploading (updated) PI in CTS (and therefore in the MRI Product Index). Also the outcome of variation worksharing procedures should be made available. It was also stressed that the information is scattered across different locations (e.g. EMA, CMDh and EC website) and it was suggested to create “instructions for use” to guide MAHs and assessors.
The CMDh was informed that related issues were raised by companies at the 17th Industry Stakeholder Platform – Operation of EU Pharmacovigilance.
It was stressed that any action should keep in mind the limited capacities of NCAs. Therefore, digital solutions should be envisaged, where possible.
The CMDh agreed to form a small group to further discuss the issues raised. A call for volunteers will be sent.
List of the active substances included in the work-sharing procedures for which data has been submitted in accordance with Art. 45 of the Paediatric Regulation
The updated list is available for download here.
Updated Post-Authorisation document from the EMA
The EMA has published the post-authorisation document (updated on 4 November 2022) entitled European Medicines Agency post-authorisation advice for users of the centralised procedure. In the updated document, responses to the following questions were updated in November 2022:
- 3.7. How shall I present my type II Variation application?
- 3.8. How shall I present my application for a new or modified therapeutic indication?
- 3.16. When do I have to submit revised product information? In all languages?
Here you can view the track changed and clean versions of the document.
List of safety concerns per approved Risk Management Plan (RMP) of active substances per product
The updated list, Rev. 35 is available for download here.
Step 2 – Nitrosamine detected response template
This template has been updated (Rev. 5 of November 2022) and is available for download here.
Updates
| Date | Update(s) |
|---|---|
| 20 Dec 2022 | 1) The heading Report from the CMDh meeting held on 8-10 November 2022 was updated to Report and minutes from the CMDh meeting held on 8-10 November 2022 and a link added to the minutes from the meeting. 2) Items 4 to 9 were added under the updated heading. |
| 18 Nov 2022 | Item 3 added under the heading Report from the CMDh meeting held on 8 – 10 November 2022 |
| 17 Nov 2022 | A small number of items from the report from the CMDh meeting held on 8-10 November 2022 added. |