IX.C.1. Roles and responsibilities

IX.C.1.1. Responsibilities of the marketing authorisation holder in the EU

The marketing authorisation holder in the EU should continuously monitor the safety of their medicinal products and inform the authorities of any new information that might have an impact on the marketing authorisation [DIR Art 23(2), REG Art 16(2)]. This includes information that meets the definition of an emerging safety issue (see IX.A.1.1. and IX.C.2.).

The continuous monitoring of EudraVigilance is a legal requirement in the EU [IR Art 18]. Signals detected through the continuous monitoring of EudraVigilance data should be handled according to the principles outlined in IX.C.3. and IX.C.4.

Signals detected through other sources should be handled according to the marketing authorisation holder’s own signal management process, taking into account the general principles outlined in IX.B.. Such signals should be reported to the competent authorities in the EU as appropriate, taking into account the general obligations of the marketing authorisation holder to keep their product information up-to-date throughout the product’s lifecycle by variation applications and to present comprehensive signal information in PSURs (see GVP Module VII). The options and timelines outlined in IX.C.4. solely apply to signals detected through the continuous monitoring of EudraVigilance data.

Signals, from any source, that meet the definition of emerging safety issues (see IX.A.1.1.) should be notified to the Agency and the competent authorities in Member States in accordance with the process outlined in IX.C.2.

The marketing authorisation holder should 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)] (see IX.C.6.).

Marketing authorisation holders shall keep their product information up-to-date in the light of scientific knowledge, including the assessments and recommendations made public via the European medicines web-portal [IR Art 11(1)(f), DIR Art 23(3), REG Art 16(3)] (see IX.C.9.).

IX.C.1.2. Responsibilities within the EU regulatory network

The competent authority of each Member State shall be responsible for monitoring the data originating in the territory of that Member State [IR Art 18(4)].

Member States and the Agency should validate and prioritise signals they have detected or that have been brought to their attention from any source, including EudraVigilance (see IX.B.3. and IX.B.4.).

All Member States shall be responsible for monitoring the data in the EudraVigilance database in accordance with Articles 107h(1)(c) and 107h(3) of Directive 2001/83/EC [IR Art 22(4)]. Within the EU regulatory network, the Agency takes the lead for EudraVigilance monitoring, signal detection and signal validation for active substances contained in at least one centrally authorised product. Signals validated by the Agency should be confirmed (or not) by the PRAC rapporteur for the concerned centrally authorised product. For active substances only contained in nationally authorised products, Member States take the lead for EudraVigilance monitoring, signal detection, validation and confirmation. For these substances, a worksharing is foreseen whereby Member States may agree within the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) to appoint a lead Member State to monitor EudraVigilance data, detect, validate and confirm signals on behalf of the other Member States [IR Art 22(1)]. A co-leader may also be appointed to assist the lead Member State in the fulfilment of its tasks [IR Art 22(1)]. For active substances contained in nationally authorised products authorised in more than one Member State and for which no lead Member State has been appointed, the national competent authority should perform signal validation and confirmation of the signals it has detected.

The PRAC is responsible for the prioritisation and analysis of signals that have been confirmed by the PRAC rapporteur or (lead) Member State [DIR Art 107h(2), REG Art 28a(2)]. The assessment of such confirmed signals is led by the rapporteur appointed by the PRAC at the stage of analysis and prioritisation (see IX.C.6.).