III.A. Introduction

This Module contains guidance on the planning, conduct, reporting and follow-up of pharmacovigilance inspections in the EU and outlines the role of the different parties involved. General guidance is provided under III.B., while III.C. covers the overall operation of pharmacovigilance inspections in the EU.

In order to determine that marketing authorisation holders comply with pharmacovigilance obligations established within the EU, and to facilitate compliance, competent authorities of the Member States concerned shall conduct, in cooperation with the Agency, pharmacovigilance inspections of marketing authorisation holders or any firms employed to fulfil marketing authorisation holder’s pharmacovigilance obligations. Such inspections shall be carried out by inspectors appointed by the national competent authorities and empowered to inspect the premises, records, documents and pharmacovigilance system master file (PSMF) of the marketing authorisation holder or any firms employed by the marketing authorisation holder to perform the activities described in Title IX of Directive 2001/83/EC in accordance with Articles 111(1) and 111(1)(d) (Directive is referenced as DIR). In particular, marketing authorisation holders are required to provide, on request, the pharmacovigilance system master file, which will be used to inform inspection conduct [DIR Art 23(4) and Regulation (EC) No 726/2004 Article 16(4) (Regulation is referenced as REG) (see Module II).

The objectives of pharmacovigilance inspections are:

• to determine that the marketing authorisation holder has personnel, systems and facilities in place to meet their pharmacovigilance obligations;
• to identify, record and address non-compliance which may pose a risk to public health;
• to use the inspection results as a basis for enforcement action, where considered necessary.

For marketing authorisation holders of centrally authorised products, it is the responsibility of the supervisory authority for pharmacovigilance to verify, on behalf of the EU, that the marketing authorisation holder for the medicinal product satisfies the pharmacovigilance requirements laid down in Directive 2001/83/EC [REG Art 19]. The supervisory authority for pharmacovigilance shall be the competent authority of the Member State in which the pharmacovigilance system master file is located [REG Art 18(3)]. According to Article 7(1) of the Commission Implementation Regulation (EU) No 520/2012 (Implementing Regulation is referenced as IR) the pharmacovigilance system master file shall be located either at the site in the Union where the main pharmacovigilance activities of the marketing authorisation holder are performed or at the site in the Union where the qualified person responsible for pharmacovigilance operates. The supervisory authority may conduct pre-authorisation inspections to verify the accuracy and successful implementation of the existing or proposed pharmacovigilance system [REG Art 18(3)].

For marketing authorisation holders of non-centrally authorised products (i.e. nationally authorised products, including those authorised through the mutual recognition or the decentralised procedure), it is the responsibility of the competent authority of the Member State concerned, in cooperation with the Agency, to ensure by means of inspection that the legal requirements governing medicinal products are complied with. This cooperation shall consist of the sharing of information between national competent authorities and the Agency concerning inspections that are planned and those that have been conducted [DIR Art 111(1)].

Pharmacovigilance inspection programmes will be implemented, which will include routine inspections scheduled according to a risk-based approach and will also incorporate “for cause” inspections, which have been triggered to examine suspected non-compliance or potential risks, usually with impact on a specific product(s).

There shall be cooperation between national competent authorities and the Agency to minimise duplication and maximise the use of available resources. National competent authorities and the Agency will make use of the shared information on planned and conducted inspections to facilitate this and to adapt the scope and/or timing of their inspections.

The results of an inspection will be provided to the inspected entity [DIR Art 111(3) and 111(8)], who will be given the opportunity to comment on any non-compliance identified [DIR Art 111(8)]. Any noncompliance should also be rectified by the marketing authorisation holder in a timely manner through the implementation of a corrective and preventive action plan.

If the outcome of the inspection is that the marketing authorisation holder does not comply with the pharmacovigilance obligations, the Member State concerned shall inform the other Member States, the Agency and the Commission in accordance with section III.C.1 [DIR Art 111(8)].

Sharing of information and communication between inspectors and assessors from the Pharmacovigilance Risk Assessment Committee (PRAC) and from the Committee for Medicinal Products for Human Use (CHMP), is very important in relation to issues of Union interest and, where considered appropriate, for the proper follow-up of inspections and the provision of recommendations on actions to be taken.

Where appropriate, the Member State concerned shall take the necessary measures to ensure that a marketing authorisation holder is subject to effective, proportionate and dissuasive penalties [DIR Art 111(8)]. Regulation (EC) No 658/2007 also empowers the Commission to impose financial penalties on marketing authorisations holders to ensure the enforcement of certain obligations connected with marketing authorisations for medicinal products granted in accordance with Regulation (EC) No 726/2004.

Information on the conduct and outcome of pharmacovigilance inspections and the follow-up and evaluation of the consequences may be made publicly available as part of the overall transparency of pharmacovigilance activities.