RMP: risk management plan

Article 8(3)(iaa) of Directive 2001/83/EC requires every application for a marketing authorisation to include a risk management plan describing the risk management system the applicant will introduce for the product, with a summary. GVP Module V sets out the content and the EU RMP template structures it: a safety specification of important identified risks, important potential risks and missing information; a pharmacovigilance plan with routine and additional activities such as post-authorisation safety studies; a plan for risk minimisation measures, routine and additional; and a public summary. Article 21a of the Directive lets authorities make the measures in the plan conditions of the authorisation.

The plan is assessed by the PRAC for centrally authorised products and by the reference member state or national authority otherwise, and the agreed version is referenced in the authorisation. Additional risk minimisation measures, such as educational materials, prescriber checklists or controlled access programmes, are agreed in principle in the plan but their wording and distribution are agreed with each national authority. Generic applicants submit a plan too, usually aligned to the reference product's safety concerns and in a reduced format where the guidance allows.

The plan is a living document. Updates are submitted when new information changes the safety concerns or the planned activities, with a PSUR or a variation that affects the plan, or when an authority asks. Most updates are Type II variations, although some administrative updates can be made in lower categories, and the version history must be kept clear so that the authority can see what changed.

What goes wrong: safety concerns copied from the reference product without checking they still apply; study milestones in the pharmacovigilance plan that pass without a submission; additional measures agreed in the plan but never rolled out in some Member States; and plan versions that drift from the product information so that the two describe different risks. Inspectors check all of these against the pharmacovigilance system master file. Products authorised before 2012 have no plan unless one was later required, and a holder bringing such a product into a new procedure, for example a repeat-use wave, should expect to be asked for one.