There is only one approved RMP at any time for a medicinal product. Consequently, any time an updated RMP is approved as part of a procedure (e.g. variation, renewal, PSUR), this RMP becomes the approved RMP of the product, and any previous version becomes obsolete. Therefore, MAHs should carefully consider the planning of RMP submission, to make sure that the approved RMP always contains the most up-to-date information on the pharmacovigilance planning and risk minimisation measures.
Given the content-based requirements for RMP submission, it is expected that there will be only few procedures where an RMP update should be included. The MAH should consider whether an RMP is really required with the procedure that is in preparation for submission. Early discussion with the regulators should facilitate the submission, to avoid unnecessary RMP submissions and assessment; parallel procedures warranting RMP updates should be avoided as much as possible.
MAHs are strongly encouraged to streamline RMP amendments and submissions, in co-operation with the EMA for the centrally authorised products, in order to facilitate RMP assessments throughout the product life-cycle.
There are two alternative approaches to the handling of different RMP versions for which the assessment is overlapping, and the MAH should choose the option that facilitates the assessment taking into account anticipated timelines for the finalisation of the procedures.
Whenever separate applications affecting the RMP are submitted in parallel, in order to facilitate the review, it is generally agreed that the MAH initially and whenever appropriate during the procedure submits one joint draft RMP file as a 'working document'. This single RMP document should include all data consequential to the concerned procedures running in parallel . To facilitate the assessment, the proposed RMP changes should be marked (e.g. with different colour code), to differentiate changes specific to each procedure (example: new safety concerns derived from an extension of indication in a new population should be marked differently from the changes in the Pharmacovigilance Plan consequential to (early) termination of a study and initiation of another one as a consequence of the limited safety data gathered in the ended study).
If the parallel applications reach the finalisation stage at the same time, the consolidated RMP version will be adopted by the relevant Committee and will become the approved version of the RMP.
If the applications do not reach the finalisation-stage at the same time, at the time of the first opinion for the parallel procedures, the MAH will need to provide for review and approval a final RMP version including only the agreed changes related to the scope of the variation application for which the CHMP is about to adopt an opinion. The joint RMP 'working document' will continue to be used in the context of the remaining ongoing procedure(s).
Example: A safety variation is triggered whilst an extension of indication procedure is ongoing, both requiring significant changes in the RMP (new safety concern in the new indication; another safety concern and a new imposed PASS in the safety variation). The RMP for the safety variation can be built upon the RMP document submitted with the extension of indication.
Option A: A joint RMP document including changes relevant to both procedures could be submitted with both the responses to the RSI in the extension procedure, and with the initial submission for the safety variation:
- If both procedures reach the Opinion stage at the same time, than the joint RMP will be adopted and become the approved RMP.
- If however the extension of indication requires a second RSI, and is most likely to be finalised after the parallel safety variation, the MAH will then have to submit before the opinion for the safety variation an RMP including only the safety concern and the new study related to the safety variation data. This version of the RMP will be checked for consistency and approved with the safety variation opinion. The updated joint RMP 'working document', including the changes consequential to the responses to the second RSI for the extension of indication will continue to be assessed within the extension of indication procedure. This joint RMP will be considered the approved RMP once the extension of indication variation reaches opinion.
A graphical representation for option A is included below:
Option B: Alternatively, it might be more appropriate when parallel procedures will follow very different assessment timetables to opt for an approach similar to the handling of parallel procedures with product information changes; the RMP submitted with each procedure should only include the changes related to that procedure:
- an updated version of the RMP is submitted as a type II variation to reflect the changes in the safety profile derived from post-marketing reporting. This RMP version should include only the changes related to the RMP update.
- subsequently or at the same time, another RMP update is submitted as part of a type II variation for the extension of indication. For this application, the RMP version only includes the changes that are consequential to the extension of indication (i.e. not the changes related to the safety variation.
If both procedures conclude at the same time, the MAH is expected to merge the two RMP documents for approval by the Opinion time.
If the RMP update variation is approved before the extension of indication procedure, the RMP submitted will be adopted with the relevant changes and the MAH can submit a consolidated RMP version as part of the MAH's responses to an RSI for the extension of indication. This RMP version includes then the changes approved as part of the recently finalised safety variation (as clean text) as well as the changes related to the extension of indication (with track changes).
The option B can be illustrated as follows:
Regardless of the approach chosen, the MAH should always provide a clear description of the scope(s) of the submission in the cover letter and the changes implemented in the RMP including references to related (previous/parallel) regulatory procedure(s) (see also Question 8 below).
