XVI.A. Introduction

A marketing authorisation for a medicinal product in the EU may be granted subject to taking certain measures for ensuring its safe use to be included in the risk management system [based on DIR Art 21a and REG Art 9(4)(ca)]. These measures support keeping the risk-benefit balance of a medicinal product (see GVP Annex 1) positive, which is a prerequisite for granting and maintaining its marketing authorisation. A risk management system is a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including the assessment of the effectiveness of those activities and interventions [DIR Art 1(28b)], and is described in the risk management plan (RMP) of the product [DIR Art 1(28c)] (see GVP Module V). The objectives of ensuring the safe use of the medicinal product and minimising risks, including their adverse health outcomes, are facilitated by risk minimisation measures (RMM).

In terms of tools, RMM are categorised into routine and additional RMM. The summary of product characteristics (SmPC) is the fundamental routine RMM tool, where the risk and intended actions for risk minimisation are described. This forms the basis for other routine RMM and, where required, additional RMM. Additional RMM tools are meant to emphasise the information on the risk and the intended actions for risk minimisation and to support and/or control the adherence to the intended actions.

For the purpose of RMM, the marketing authorisation holder shall evaluate all information scientifically, consider options for risk minimisation and prevention, and take appropriate measures as necessary [DIR Art 104(2)]. Likewise, the competent authorities in Member States shall evaluate all information scientifically, consider the options and take regulatory action concerning the marketing authorisation as necessary [DIR Art 101(2)], and the Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) shall provide recommendations relating to risk management systems [based on REG Art 56(1)(aa)]. Further, the marketing authorisation holder [DIR Art 104(3)(c) and (d)] as well as the competent authorities in Member States and the Agency [based on DIR Art 107h(1)(a), REG Art 28a(1)(a) and REG Art 56(1)(aa)] shall monitor the outcomes of RMM contained in the RMP or any other conditions or restrictions with regard to the safe and effective use of the medicinal product.

Planning for developing, implementing and evaluating RMM should begin early during the development phase of the medicinal product, as part of the proactive risk management system to be set up by the applicants for a marketing authorisation, to whom the guidance for marketing authorisation holders in this Module is applicable too.

It is recognised that risk minimisation is an evolving area for which new approaches and methods will emerge. Implementing RMM in healthcare for patient safety requires approaches from the implementation sciences as well as engagement across different stakeholders for patient-centred healthcare. As technology advances, the potential of supporting risk minimisation through digital applications may be considered.

The terminology for this GVP Module is presented in XVI.A.. XVI.B. provides the principles and tools of RMM, points to consider for their selection as well as guidance for their development, implementation and evaluation, with a view to an overall risk-proportionate and consistent approach to risk minimisation. XVI.C. describes the related responsibilities of marketing authorisation holders and competent authorities of the EU regulatory network. The Module also reflects on the engagement with healthcare professional and patient representatives.

This GVP Module should be read together with the Addenda of GVP Module XVI and other GVP Modules as referenced, the CHMP Guideline on Safety and Efficacy Follow-up – Risk management of Advanced Therapy Medicinal Products1 , the PRAC Good Practice Guide on Risk Minimisation and Prevention of Medication Errors2 , the EMA Guidance on Post-Authorisation Safety Studies3 and the EMA PostAuthorisation Guidance4 . Marketing authorisation holders should also follow guidance in place in Member States.

In this GVP Module, all applicable legal requirements are referenced as explained in the GVP Introductory Cover Note and are usually identifiable by the modal verb “shall”. Guidance for the implementation of legal requirements is provided using the modal verb “should”. Directive 2001/83/EC as amended is referenced as ‘DIR’, Regulation (EC) No 726/2004 as amended as ‘REG’ and the Commission Implementing Regulation (EU) No 520/2012 as amended as “IR”.