Last updated: 5 March 2024
See updates at the end of the post.
Q&A – Pharmacovigilance Legislation Regulation (EU) No 1235/2010 and Directive 2010/84/EU updated
The above document has been updated. Here, you can view the track changed and clean versions. The response to Q2 How should I submit a new RMP or an updated RMP to update my dossier? (December 2019).
Source: HMA
Compilation of QRD decisions on stylistic matters in product information
You can view the updated document of 29 February 2024 Rev 23 here.
Rev.23 Changes since last revision: Inclusion of new guidance for ‘INN: display on packaging when product name is MAH+INN’ and ‘Package leaflet: ATMPs with orphan designation, not intended to be delivered directly to patients’. Revised guidance for ‘Abbreviations and acronyms’, ‘E-numbers’, ‘Number separators (DK)’, ‘Strength: sodium chloride solution’, ‘Use of English or Latin (FI, IT and SE requirements)’ and ‘Wallet packs: particulars on blisters sealed inside a wallet’. The use of ‘must’ vs ‘should’ has been revised throughout to avoid confusion between ‘obligation’ and ‘recommendation’.
Source: EMA
Statistics for New Applications (MRP/DCP), Variations, Referrals and Paediatric Worksharing procedures in 2023
You can view the document with the above title here.
CMDh Best Practice Guide on Multilingual Packaging
The guide with the above title has been updated. Here, you can view the track changed (Oct 2021) and clean (Feb 2024) versions of the document. There are substantial changes throughout the document.
Template corrections
The following templates have been corrected:
- Lead Member State PSUR Follow-Up assessment report – You can view the corrected (Feb 2024) template here. (Source: HMA)
- Template Preliminary Renewal Assessment Report – You can view the corrected (feb 2024) template here. (Source: HMA)
- Template Assessment Report MRP Overview -You can view the corrected (Feb 2024) template here. (Source: HMA)
- Assessment report Mutual recognition Procedure- You can view the corrected (Feb 2024) template here.
Launch of new HMA-EMA catalogues of real-world data sources and studies
EMA and the Heads of Medicines Agencies (HMA) have launched two public electronic catalogues: one for real-world data (RWD) sources and one for WD studies.
The catalogues help medicines regulators, researchers and pharmaceutical companies to identify the most suitable data sources to address specific research questions and support the assessment of study protocols and results. They aim to promote transparency, encourage the use of good practices, and build trust in research based on RWD.
- The catalogue for RWD sources enhances and replaces the ENCePP Resources Database, an EMA-coordinated index of resources of available research organisations, networks and data sources in the fields of pharmacoepidemiology and pharmacovigilance within Europe.
- The catalogue for RWD studies expands and replaces the European Union electronic register of post-authorisationstudies (EU PAS Register®).
Further information is available at the links below.
Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 5-8 February 2024
EMA’s safety committee (PRAC) is reminding healthcare professionals of the risk of serious and potentially fatal adverse reactions with Paxlovid (nirmatrelvir, ritonavir) when used in combination with certain immunosuppressants that have a narrow safe dosage range (where small changes in the dose can lead to serious adverse reactions), due to drug-drug interactions reducing the body’s ability to eliminate these medicines.
You can view more information on the above and other the meeting highlights from this meeting here.
Report and minutes from the CMDh meeting held on 23-24 January 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. Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP
The CMDh agreed an update of the Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP.
- Q&A 33 has been updated to remind MAHs with multicountry packs involving the UK to consider taking appropriate measures before the date on which Regulation (EU) 2023/1182 becomes applicable.
- Reference is made to the recently published EMA guidance Questions and answers to stakeholders on the implications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use. Q&A 34 has been updated to clarify the concept of reference medicinal product from the UK, in line with the discussion at the September 2023 CMDh meeting.
The updated document has been published on the CMDh website under “Brexit”. Here, you can view the track changed (Sept 2023) and clean (Jan 2024) versions of the guide.
2. Questions and Answers on nitrosamines
In December 2023, 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&A 3 and Q&A 10 have been updated to include guidance on the handling of non-mutagenic nitrosamine impurities (NMI).
- Q&A 9 has been updated to clarify sensitivity requirements for analytical methods. Q&A 10 has been updated to include Ames test acceptability timelines.
The new Q&As have been published on the EMA website and a link is provided from the CMDh website under “Nitrosamine impurities”. Here, you can view the updated Q&A.
3. Update of CMDh templates
In April 2023, the CMDh agreed to remove the reference to Art. 10(3) from the footnote of the templates for CMS comments during DCP (D100, D145, D205) in line with the Notice to Applicants, which states that the product name in the RMS and in all CMS must be the same only for Art. 10(1) applications with a centrally authorised product as reference medicinal product.
The CMDh also noted this inconsistency in the DCP overview assessment report template (including instructions) and the CMS comments during MRP and agreed to update them accordingly.
The updated templates have been published on the CMDh website under “Templates > Assessment Reports”. Links to the updated templates are provided below:
- Template DCP: RMS Day 70 Perliminary Assessment report – RMS DAy 120 Draft Assessment Report – Overview and list of questions and outstanding issues – You can download the updated template (January 2024) here.
- Template CMS comment in MRP – You can download the updated template (January 2024) here.
4. Harmonisation of marketing authorisations by requesting worksharing procedures
Following the discussion and agreement in December to start a pilot to ask MAHs of innovator products, for which disharmonised product information is detected, to harmonise their PI via variation worksharing, the CMDh discussed the proposed template letter to be sent. No comments on the letter have been received since the December meeting. The letter was agreed by the CMDh.
The CMDh discussed a first example for a product for which disharmonised PI has been detected.
A letter will be sent to the MAH by the CMDh.
For the further proceedings, it was clarified that the intention is not to draw up a list of potential candidates of products for SmPC harmonisation, but to bring possible candidates to the attention of CMDh on an ad-hoc basis, when they are identified. For a worksharing variation to be possible, all the products authorised in different MSs have to belong to the same MAH.
5. Suspension of MA due to impossibility of contact with the MAH
Following the discussion in the November CMDh meeting, Portugal (PT) informed the CMDh about the actions taken at national level for a product for which the MAH went bankrupt and could not be reached anymore.
- PT has suspended the MAs based on the fact that the MAH is unable to fulfil its obligations and will revoke the MAs if the MAH fails to carry out its obligations within a certain period.
- The actions were considered as an administrative step and no further actions at EU level were considered necessary.
- The CMDh agreed that no further action at EU level is necessary. MSs can take similar actions at national level, if needed.
6. Request for an additional year of market protection according to Art. 10(1)
The CMDh was reminded of the agreement reached in November 2019 that missing data for justification of an additional year of marketing protection should be classified as “other concern” rather than “major objection”- when the application as such would be approvable. It was noted that in the centralised procedure the issue would be raised as MO under a specific heading ‘Additional year of marketing protection’ without implying a negative opinion on the procedure.
7. Acceptability of single ASMF for co-crystals containing more than one active substance
Based on a request from a company to submit a single ASMF for co-crystals containing more than one active substance in an upcoming generic DCP application, the CMDh discussed if such a submission is acceptable or if two or more separate ASMFs should be submitted instead. The company considers the active substance to be a complex molecule and a single active substance.
- Reference was made to the “Reflection paper on the chemical structure and properties criteria to be considered for the evaluation of new active substance (NAS) status of chemical substances EMA/CHMP/QWP/104223/2015” and the “Reflection paper on the use of cocrystals of active substances in medicinal products EMA/CHMP/CVMP/QWP/284008/2015”.
- It was agreed that a final decision on the acceptability of only one ASMF cannot be taken during validation and based on the information available at this stage.
- It needs to be ensured that sufficient information on the manufacturing of both active substances and the co-crystal is available in the dossier. This would be a matter of assessment.
- The company can be informed that the submission of one ASMF would not block the validation, but it could be possible that during assessment it will be decided that the approach needs to be changed and two (or three) ASMFs would be needed.
8. Data exclusivity period and same Global Marketing Authorisation (GMA)
The CMDh discussed if two medicinal products could be considered to be part of the same global marketing authorisation (GMA) for the purpose of data exclusivity, based on a question submitted by a generic applicant.
- A justification why the two MAHs should be considered linked, based on the licensing history of both products, was provided.
- The CMDh agreed that the applicant has not sufficiently addressed that the current MAHs of the two products can be considered as the ‘same MAH’, either as belonging to the same mother company, as licensees, or as exercising concerted practices concerning the placing on the market of the medicinal product in different Member States and, therefore, the two products cannot be considered as belonging to the same GMA.
9. Generic application identical to the (European) Reference Medicinal Product (RefMP)
The CMDh discussed the validation of an (auto-)generic application (Article 10(1) of Directive 2001/83/EC). The applicant is also the MAH of the European Reference Medicinal Product (ERP) authorised in PL under Article 10a of Directive 2001/83/EC, but not authorised in the RMS or any of the CMSs of the generic application. The products applied for and the RefMP are identical. Therefore, no BE study has been submitted.
- The CMDh discussed and agreed by majority that the submission of the generic application does not constitute an infringement of Article 18 of Directive 2001/83/EC as the applicant used the DCP and did not submit the application purely nationally in one MS.
- The application can therefore be validated, if no other concerns remain.
- Reference was made to the CMDh Q&As on Applications for MA (Question 4), which recommends that in case of an application based on an identical dossier of the same product the same RMS should be used for the “duplicate” marketing authorisation, where possible, in accordance with the CMDh recommendations on multiple/duplicate applications in MRP and DCP, or that one of the CMSs involved in the previous procedure should be chosen as RMS.
- However, it should be noted that in accordance with the mentioned guidance a “duplicate” application should have the same legal basis as the first MA.
- One MS considered that the application would constitute an infringement of Article 18 as there is no overlapping MS.
Updates
| Date | Update(s) |
|---|---|
| 5 Mar 2024 | Added new section, Q&A – Pharmacovigilance Legislation Regulation (EU) No 1235/2010 and Directive 2010/84/EU updated. |
| 1 Mar 2024 | The following three new sections were added: 1) CMDh Best Practice Guide on Multilingual Packaging 2) Statistics for New Applications (MRP/DCP), Variations, Referrals and Paediatric Worksharing procedures in 2023 3) Compilation of QRD decisions on stylistic matters in product information |
| 29 Feb 2024 | New section Template corrections added. |
| 27 Feb 2024 | 1) Heading Report from the CMDh meeting held on 23-24 January 2024 updated to Report and minutes from the CMDh meeting held on 23-24 January 2024 2) Link added to the minutes from the meeting. 3) Item 4 under the heading. |
| 15 Feb 2024 | Added new section Launch of new HMA-EMA catalogues of real-world data sources and studies |
| 9 Feb 2024 | Added section Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 5-8 February 2024. |