XVI.C.3. Responsibilities of the EU regulatory network

XVI.C.3.1. Competent authorities in Member States

The general role of the competent authorities in Member States for pharmacovigilance in the EU is described in GVP Module I and for risk management in particular in GVP Module V.

Regarding risk minimisation activities, Member States shall by means of their competent authority’s pharmacovigilance system evaluate all information scientifically, consider options for risk minimisation and prevention and take regulatory action concerning marketing authorisations as necessary [DIR Art 101(2)].

For medicinal products authorised nationally by competent authorities in Member States, including those authorised through the mutual recognition procedure or the decentralised procedure, the competent authorities in Member States may impose in the marketing authorisation (see XVI.C.1.1.) an obligation on the marketing authorisation holder to describe and operate a risk management system in the RMP (see XVI.C.1.2.) [DIR Art 104a(2)] and shall monitor the outcome of RMM and assess updates to the risk management system [DIR Art 107h(1)(a) and (b)]. For products authorised nationally through the mutual recognition procedure or the decentralised procedure, the competent authority in a Member State may require additional RMM only for this Member State.

For nationally authorised products subject to a safety-related EU referral procedure, the European Commission may adopt a decision addressed to Member States for the implementation of conditions or restrictions of the marketing authorisation, such as RMM, to be adhered to by the competent authorities in Member States [DIR Art 107k(2) and Art 33 and 34].

For medicines authorised by the European Commission through the centralised procedure, the European Commission may adopt a decision addressed to Member States for the implementation of conditions or restrictions of the marketing authorisation [DIR Art 127a], such as RMM, to be adhered to by the competent authorities in Member States. For centrally authorised products, the competent authorities in Member States shall collaborate with the Agency to monitor the outcomes of RMM and assess updates to the risk management system [based on REG Art 28a(1)(a) and (b)] (see XVI.C.3.2.).

Irrespective of the route of marketing authorisation, the competent authorities in Member States are responsible for the approval of nationally tailored additional RMM materials and the agreement of the national RMM dissemination plans (see XVI.B.4.) and should therefore ensure prompt consideration of the respective submissions by marketing authorisation holders (see XVI.C.2.1.).

Because of the specifics and differences of the healthcare systems in Member States and of how particular risk(s) are managed within these systems, some RMM may need to be implemented differently in Member States. As the implementation of additional RMM takes place at national level, Member States may tailor the required conditions and restrictions for risk minimisation to their national legal requirements and local healthcare systems. The national tailoring of RMM materials should address the specifics of the healthcare systems in Member States, e.g. applicable subgroups of the target population, naming of the RMM tool and full wording of the RMM material in the official language(s), additional information items, design and formatting, dissemination, with a view to best support the implementation of the RMM in healthcare. Member States may also have specific requirements for using educational/safety advice materials to document healthcare processes, including confirmations through signatures of the healthcare professional or the patient. Especially for risk minimisation control programmes, the competent authorities in Member States should determine and discuss with the marketing authorisation holder how the applicable RMM tools can be implemented in healthcare and which RMM materials are needed for these tools in accordance with the nationally established processes for training and qualification of healthcare professionals, accreditation of healthcare facilities, healthcare documentation and information exchange, and traceability. Risk minimisation control programmes can be supported in their implementation in healthcare by national healthcare processes, e.g. restrictions in amount of medicinal product allowed per prescription or in the validity length of a prescription.

Competent authorities in Member States are encouraged to, as needed, appropriate and possible, seek input from healthcare professional and patient representatives (see XVI.B.1.4.), request from the marketing authorisation holder user-testing of additional RMM materials in the respective official language(s), and consider results from user-testing of RMM when requested from and/or submitted by the marketing authorisation holder. Interactions between the competent authorities in Member States and stakeholders responsible for implementation of RMM in healthcare (see XVI.B.1.3.) are desirable; in particular for risk minimisation control programmes such interactions may be needed to determine how their RMM tools may be best integrated in healthcare processes and which RMM materials are needed to implement the tools. Member States should verify the independence of the representatives for impartial advice, in particular the independence from marketing authorisation holders.

For the purpose of risk minimisation, the competent authorities in Member States should follow the guidance in XVI.B. and XVI.C., including the guidance on transparency in XVI.C.4.

XVI.C.3.2. The European Medicines Agency

The general role of the Agency for pharmacovigilance in the EU is described in GVP Module I and for risk management in particular in GVP Module V.

For medicinal products authorised by the European Commission through the centralised procedure, the Agency conducts the assessments, including on RMM which are to be included in the marketing authorisation (see XVI.C.1.1.) and the RMP (see XVI.C.1.2.). The imposition of such obligations shall be duly justified, notified in writing and shall include the timeframe for submission of the RMP [REG Art 21(2)] (see GVP Module V). Further, the Agency shall, in collaboration with the Member States, monitor the outcomes of RMM and assess updates to the risk management system for centrally authorised products [REG Art 28a(1)(a) and (b)].

For medicinal products authorised nationally by competent authorities in Member States, including those authorised through the mutual recognition procedure or the decentralised procedure (see XVI.C.3.1.), the Agency supports the applicable procedures relevant to RMM activities at EU level.

For nationally authorised products subject to a safety-related EU referral procedure, the Agency conducts these procedures in accordance with the legislation and guidance on Referral procedures: human medicines18 .

The Agency fulfils its legal obligations through the procedures of its Committees, for safety of medicinal products in particular the Committee for Medicinal Products for Human Use (CHMP)19 and the PRAC (see XVI.3.1.1.), and through supporting the Coordination Group for Mutual Recognition and Decentralised Procedures – human (CMDh)20 (see GVP Module I).

For the purpose of risk minimisation, the Agency should follow the guidance in XVI.B. and XVI.C., including the guidance on transparency in XVI.C.4.

XVI.C.3.2.1. The Pharmacovigilance Risk Assessment Committee

The Pharmacovigilance Risk Assessment Committee (PRAC) (see GVP Module I) shall be responsible for providing recommendations to the CHMP and the CMDh on any question relating to pharmacovigilance activities in respect of medicinal products for human use and on risk management systems and shall be responsible for monitoring the effectiveness of those risk management systems [REG Art 56(1)(aa)], which includes the RMM and the RMM effectiveness evaluation studies.

Therefore, the PRAC should provide assessments of risks and consider the need for RMM applying the guidance in XVI.B.1., XVI.B.2., XVI.B.3. and XVI.B.6., and if they recommend RMM, specify the tools and messages (see XVI.A.1.1.) in the PRAC recommendation. The PRAC recommendation may also relate to the development and dissemination of additional RMM materials, including the need for a DHPC (see XVI.B.4.2.1.).

Further, the PRAC recommendation may include studies to be requested from the marketing authorisation holder for evaluating RMM effectiveness. The PRAC should assess as appropriate the protocols and results of these studies for regulatory follow-up, taking into account the guidance in XVI.B.5. and XVI.B.6. and other available guidance.

To improve regulatory decision-making on RMM, the PRAC has adopted a strategy for measuring the impact of pharmacovigilance activities21 .

XVI.C.3.2.2. Engagement with patients and healthcare professionals at EU level

The PRAC engages with patient and healthcare professional representatives to support its decisionmaking on risk minimisation (see XVI.B.1.4.). For their medicinal product assessments, the PRAC therefore involves its members representing patients and healthcare professionals in discussing options for RMM and their implementability for anticipated RMM effectiveness (see XVI.B.1.3.) and considers further involvement of patient and healthcare professional representatives as needed, appropriate and possible for the assessment through the ways and forums established by EMA’s frameworks for engaging with partners and networks22 . These ways and forums include written consultations, scientific advisory groups, ad hoc expert groups and public hearings (see Rules of Procedure on the Organisation and Conduct of Public Hearings at the Pharmacovigilance Risk Assessment Committee23).

The PRAC may also seek their input on general matters relevant to implementing RMM in healthcare from its members representing patients and healthcare professionals and further representatives from eligible organisations belonging to EMA’s partners and networks.