II.C.1. Responsibilities

II.C.1.1. Marketing authorisation holders and applicants

Marketing authorisation holders shall have a pharmacovigilance system in place to ensure the monitoring and supervision of one or more medicinal products. They are also responsible for introducing and maintaining a PSMF that records the pharmacovigilance system in place with regard to one or more authorised products [DIR Art 23(4), Art 104(3)(b), REG Art 16(3a)]. In accordance with Articles 8(3)(ia) and 104(3) of Directive 2001/83/EC a single QPPV shall be appointed to be responsible for the establishment and maintenance of the pharmacovigilance system described in the PSMF.

Applicants are required, at the time of initial marketing authorisation application, to have in place a summary of the pharmacovigilance system that records the system that will be in place and functioning at the time of granting of the marketing authorisation and placing of the product on the market. During the evaluation of a marketing authorisation application the applicant may be requested to provide a copy of the PSMF for review.

The applicant/marketing authorisation holder is responsible for establishing the PSMF in an EU country (at any marketing authorisation holder or contractual partner site including the site of a contractor or marketing partner) and for registering the master file location with the competent authorities in the marketing authorisation application (as applicable) and in the Article 57 database. The PSMF shall describe the pharmacovigilance system in place at the current time. Information about elements of the system to be implemented in future may be included, but these should be clearly described as planned rather than established or current.

The PSMF creation, maintenance in a current and accessible state (permanently available for audit and inspection purposes) and provision to competent authorities can be outsourced to a third party, but the marketing authorisation holder retains ultimate responsibility for compliance with the legal requirements.

Marketing authorisation holders are responsible for notifying the Agency immediately of any change in the QPPV details and the PSMF location details. The Agency shall update accordingly the EudraVigilance database referred to in Article 24(1) of Regulation (EC) No 726/2004 and, where necessary, the European medicines web-portal referred to in Article 26(1) of Regulation (EC) No 726/2004 [IR Art 4(4)].

II.C.1.2. National competent authorities

The national competent authorities are obliged to supervise the pharmacovigilance systems of marketing authorisation holders [Recital 7 of Directive 2010/84/EU]. As part of this requirement, they will review the summary information about the pharmacovigilance system included in the marketing authorisation application. The full PSMF may be requested at any time, for example, to review the summary of the pharmacovigilance system of an applicant that has not previously held a marketing authorisation in the EU or where specific concerns about the pharmacovigilance system and/or the product safety profile exist, and in preparation for an inspection (see GVP Module III). Information concerning changes to the summary information or content of the PSMF will also be used to inform inspection planning and conduct.

For centrally authorised products, the Member State where the master file is located will become the supervisory authority [Recital 22 of Regulation (EU) No 1235/2010, REG Art 18(3)]. For pharmacovigilance systems that include centrally authorised products, as well as nationally authorised products, including those authorised through the mutual recognition or the decentralised procedure, national competent authorities will supervise the pharmacovigilance system in co-operation with the supervisory authority and the Agency. For pharmacovigilance systems that do not include centrally authorised products, individual national competent authorities remain responsible for supervision of the pharmacovigilance system and will work together to minimise duplication of effort.

National competent authorities will share information about pharmacovigilance systems and use the information to inform national risk-based inspection programmes. Inspectors from national competent authorities will report non-compliance with the requirements of legislation and guidance, including both non-compliance with the requirements for the PSMF and the pharmacovigilance system (see GVP Module III).

II.C.1.3. The European Medicines Agency

For centrally authorised products, the Agency co-ordinates the inspections of marketing authorisation holders or their service providers. Supervision of the pharmacovigilance system is based on the location of the PSMF, with the Member State where the master file is held becoming the supervisory authority [REG Art 18(3)]. The Agency may request the PSMF in order to fulfil its co-ordination role.

The main responsibility of the Agency, in relation to PSMFs, is the maintenance of EU wide databases, dissemination of information and coordination of EU wide activities. To this effect, the Agency, in collaboration with the Member States and the European Commission, is responsible for the set up and maintenance of the European medicines web-portal for the dissemination of information on medicinal products authorised in the EU [REG Art 26]. The Agency will manage the product list described in Article 57 of Regulation (EC) No 726/2004 which provides a practical mechanism for maintaining upto-date information about the location of the PSMF, the QPPV contact information and the products relevant to the pharmacovigilance system described in the PSMF. The list of the locations in the EU where PSMFs are kept will be made public via the web-portal [REG Art 26(1)(e)].