XVI.C.1. Required risk minimisation measures and their evaluation as part of the marketing authorisation in the EU and related documents

XVI.C.1.1. Marketing authorisation, including the product information

In the EU, the marketing authorisation of a medicinal product includes the product information (i.e. the SmPC, package leaflet and labelling of the immediate and outer packaging), the specification of the legal status and the pack size, and, if required, a request for a visual reminder and/or a special warning/information for precaution on the product information as routine RMM (see XVI.B.2.2.), as well as, if required, a listing of the required additional RMM tools and a brief summary of the RMM messages (see XVI.A.1.1.) at the level of detail appropriate for the given medicinal product and risk. Therefore, RMM form an obligation on the marketing authorisation holder in the EU.

When RMM are adapted (see XVI.B.6.), the marketing authorisation is to be updated accordingly.

The specific additional requirements for reflecting a patient card in the marketing authorisation are provided in XVI.App2.5.

XVI.C.1.2. Risk management plan

The required RMM and the activities for their effectiveness evaluation should be included in the risk management plan (RMP) (see GVP Module V) of the medicinal product, which is part of its EU marketing authorisation (see XVI.C.1.1.).

The RMP part V should include the risk minimisation plan, describing, for each safety concern in the safety specification of the RMP, the RMM tools (see XVI.B.2.) with their most important intended outcomes (see XVI.B.1.2.) and the justification for each tool, and describing the development and planning activities for RMM implementation (see XVI.B.4.). It should also include a brief summary of the results of the studies evaluating RMM effectiveness as the justification for adaptations to RMM (see XVI.B.6.). Any adaptation to RMM should be accompanied by a rationale and the underlying evidence or other relevant information (for the content of the RMP part V for a biosimilar, hybrid or generic medicinal product where the marketed reference medicinal product does not have any aRMM, see XVI.C.2.2.).

RMP annex 6 should include a listing of the required additional RMM tools and their messages (see XVI.A.1.1.) at the level of detail appropriate for the given medicinal product and risk (RMM key elements).

The RMP part III on the pharmacovigilance plan and RMP part V should include a description of the activities for evaluating the effectiveness of RMM. Protocols and milestones for RMM effectiveness studies should be included in the RMP part III. Marketing authorisation holders and competent authorities may agree on indicators of success to be included in the RMP (see XVI.B.5.).

The RMP should be kept updated with adaptations to RMM (see XVI.B.6.) and new studies required for evaluating RMM effectiveness (see XVI.B.6.1.).

XVI.C.1.3. Periodic safety update report

The periodic safety update report (PSUR) shall contain the results of assessments of the effectiveness of risk minimisation activities relevant to the risk-benefit assessment [IR Art 34(3)].

Therefore, the PSUR should include in its sub-section “Effectiveness of risk minimisation (if applicable)” and the applicable sections of the PSUR EU regional appendix (see GVP Module VII) updates on the implementation (including the development and dissemination) of RMM, the results of the studies evaluating RMM effectiveness, applying the guidance in XVI.B.5., and a discussion on the possible need to adapt the RMM (see XVI.B.6.) and/or the activities required to evaluate the RMM effectiveness (see XVI.B.6.1.)