Variations may be made to the MA granted to a marketing authorisation holder for a proprietary medicinal product. These are changes to the information of the dossier submitted in the initial application of the MA.
With the entry into force of Regulation 2019/6, type IA, IB and II variations are deleted. Now two types of variation: with or without evaluation exist. Variations without evaluation become simple declarations: the list of variations that do not require an evaluation shall be determined by delegated act. This list contains the conditions to be fulfilled and the documentation to be provided, as well as a code for each variation.
Regulation 1234/2008 and the 2003 Guideline Classification will now only apply to medicinal products for human use.
The list of variations without evaluation is set out in Commission Implementing Regulation (EU) 2021/17 of 8 January 2021 establishing a list of variations that do not require an assessment, in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council.
CMDv completed the list and classification of variations requiring an assessment with a guideline: Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations.
Variations not requiring assessment (VNRA)
For variations without evaluation (Article 61), the Regulation provides that registrants will enter them directly into the medicinal products database within 30 days of their implementation. The competent authorities may then accept or reject the variation in the database and update their MA where necessary. The SPC, labelling and package leaflet shall be provided by the MA holder at the beginning of the procedure and stored in the database at the end of the procedure.
Recently the UPD has been developed in order that marketing authorisation holders (MAH) are able to apply for several variations not requiring assessment (VNRA) for several marketing authorisations (MA) called as “technical grouping”. The CMDv agreed on a stepwise approach that veterinary medicinal products (VMP) belonging to the same range (e.g. IT/V/012/001-005) can only be technically grouped.
The UPD has also been developed to allow the changes related to Qualified Person for Pharmacovigilance (QPPV) and to Pharmacovigilance System Master File (PSMF) to be automated. Indeed, the automation of the updates as a result of an approval of VNRAs related to Pharmacovigilance (PhV) (C1, C5 and C6) was released to production. This functionality, that is available for both CAPs and non-CAPs, will allow MAHs to provide the values of the PhV attributes at the time of submission, and once the Responsible authority approves the VNRAs, the system will automatically update the PhV data in the products impacted.
At the December 2022 plenary meeting the CMDv discussed the update of the UPD concerning the information related to QPPV and PSMF for already authorised VMPs and agreed that the technical grouping facilities would be extended to the changes concerning QPPV and PSMF considering that those VNRA are now automated in the UPD.
Moreover, it was also proposed that the technical grouping can only be accepted for VMPs from the same MAH with the same Member State as decision making authority for products authorised via MRP/DCP or purely nationally. This means that for those specific changes MAHs are allowed to apply for MRP/DCP/SRP and NAP in a same VNRA provided that the RMS of MRP/DCP/SRP is the same and that the NAPs are authorised in this Member State.
The other changes are currently not possible to be handled if VMPs are not from the same range of products.
Variations requiring assessment (VRA)
MA variations requiring scientific evaluation correspond to all variations that are not listed in the EC Delegated Act. There will be no list of these variations, therefore no codification, documentation or conditions to be complied with.
It will always be possible to group variations between them. It will therefore be possible to submit an application for several variations relating to the same marketing authorisation or for one variation relating to more than one MA. On the other hand, the Regulation does not state whether it is possible to group several variations for several MAs.
As regards worksharing (allocation of tasks — Article 65), the EC may, if it so wishes, lay down the detailed rules for this procedure by means of an implementing act.
The BPG of the CMDv is considered sufficient to describe this procedure.
The schedule of variations with evaluation is 60 days (can be extended to 90 days). It shall be suspended in the event of a request for additions. In case of disagreement, the procedure described in Article 54 applies (Re-examination).The applicant has the possibility, as in the case of a decentralised procedure, to request a re-examination of the RMS report.
At the end of the procedure, MS have 30 days to notify their decision after the receipt of the translations by the MA holder. The database produced must also be updated accordingly by the MS.
The holder may implement the variation only once the decision has been notified. The competent authority must set a deadline for the implementation of this variation.
The guidelines of the Coordinating Group on Mutual and Decentralised Recognition Procedures — Veterinary (CMDv) on MA variations can be found on this page: CMDv- Variations.
To apply for authorisation for a veterinary medicinal product