IX.C.6. Signal analysis, prioritisation and assessment by the PRAC

When the Agency or the competent authority in the Member State validating or confirming a signal considers that urgent action is required before the subsequent PRAC meeting, it should use the pharmacovigilance rapid alert system of the EU regulatory network to inform this network about the issue and request discussion on any potential action (see European Union Regulatory Incident Management Plan for Medicines for Human Use (19)).

The PRAC should prioritise signals taking into account the information provided by the Member State or rapporteur that confirmed the signal (see IX.B.4. and IX.C.5.). The PRAC may further amend the scope of the signal management by extending it to other active substances of the same class of medicinal products or to other related adverse reactions.

When further assessment is considered needed within the signal procedure, the PRAC should appoint a rapporteur and define a timeframe taking into account the prioritisation of the signal.

The appointed rapporteur should lead the assessment and transmit to the PRAC an assessment report. The assessment report should include a proposed recommendation and should be updated as appropriate based on comments from other PRAC members and the marketing authorisation holder(s). A template for the signal assessment report is available on the Agency’s website (20). Guidance for competent authorities in Member States is also available in the SCOPE Best Practice Guide on Signal Management (21).

The standard timeframe is two months for the submission of additional data by marketing authorisation holders and a further two months for assessment by the PRAC. Depending on the signal multiple rounds of assessment may be needed. Timetables for signal assessment are published on the Agency’s website.

Marketing authorisation holders shall collaborate with the PRAC for the assessment of the signals by providing the additional information requested [DIR Art 23(4) and REG Art 16(3a)]. Such requests are generally addressed to marketing authorisation holders of the reference medicinal products and usually consist of a cumulative review of relevant data (e.g. from spontaneous reports, clinical trials, scientific literature), together with a discussion and conclusion from the marketing authorisation holder. Marketing authorisation holders that provide data are also invited to comment on the rapporteur’s preliminary assessment report.

The detailed process for PRAC assessment of confirmed signals is shown in Figure IX.5. in IX. Appendix 1.

When the PRAC recommends assessment of the signal within another procedure (e.g. PSUR, referral, variation), the process and timelines for that procedure apply and the signal procedure is closed.