Acknowledgements

The PIPA Committee would like to thank the following members of the PIPA Training Working Party who played a major role in the development of this course:

  • Avile Rodriguez, Senior Safety Officer, Mitsubishi Tanabe Pharma Europe Ltd
  • Shirley-Ann Van Der Spuy, Qualified Person for Pharmacovigilance (QPPV) at Red Line Pharmacovigilance Ltd
  • Sharon Braithwaite, PIPA Membership and Events Co-ordinator
  • Anne Turnbull, PIPA Operations Manager

Transparency

Information on the conduct and outcome of pharmacovigilance inspections and their follow-up may be made publicly available. This will then be elaborated further in the compilation of Union procedures on pharmacovigilance inspections mentioned in Section VI: Inspection process.

Inspection fees

  • For inspections requested by the CHMP, an inspection fee(s) (and inspectors’ expenses where applicable) will be charged in accordance with the Council Regulation (EC) No 297/95 on fees payable to the European Agency for the Evaluation of Medicinal Products as amended and implementing rules applicable at the time
  • For pharmacovigilance inspections performed in the context of national, mutual recognition and decentralised procedures similar fees may or may not apply depending on the legal requirements of the Member State carrying out the inspection

5. Role of marketing authorisation holders and applicants

Marketing authorisation holders with authorised products and applicants who have submitted new applications under the centralised procedure are subject to pharmacovigilance inspections (see III.B.1.). Therefore both have responsibilities in relation to inspections, including but not limited to the following:

  • always to be inspection-ready as inspections may be unannounced
  • to maintain and make available to the inspectors on request, no later than 7 calendar days after the receipt of a request, the pharmacovigilance system master file as required by Article 23(4) of Directive 2001/83/EC and Article 16(4) of Regulation (EU) 726/2004
  • to ensure that the sites selected for inspection, which may include firms employed by the marketing authorisation holder to perform pharmacovigilance activities, agree to be inspected before the inspection is performed
  • to make available to the inspectors any information and/or documentation required for the preparation of the inspection within the deadline given or during the conduct of the inspection
  • to ensure that relevant staff involved in pharmacovigilance activities or related activities are present and available during the inspection for interviews or clarification of issues identified
  • to ensure that relevant pharmacovigilance data is accessible from at least one point in the Union [DIR Art 107(1)]
  • to ensure that appropriate and timely corrective and preventive action plans are implemented to address findings observed during an inspection, with appropriate prioritisation of critical and/or major findings

4.3 Inspection programmes (Summary)

  • A programme for routine inspections for centrally authorised products will be determined by the Agency in conjunction with the supervisory authorities of the Member States, the PhVIWG, the PRAC and the CHMP
  • These inspections will be prioritised based on the potential risk to public health, considering the factors listed in Section III: Inspection process
  • As a general approach, a marketing authorisation holder should be inspected on the basis of risk-based considerations, but at least once every 4 years
  • If the same pharmacovigilance system is used for a variety of authorisation types (centralised and national, mutual recognition and decentralised), then the results of a supervisory authority inspection may be applicable for all products covered by that system
  • This routine inspection programme will be separate from any “for cause” inspections, but if a “for cause” inspection takes place it may replace the need for one under this programme, dependent on its scope.
  • Member States are also responsible for the planning and coordination of pharmacovigilance inspections within their territory in relation to products authorised nationally or via the mutual recognition or decentralised procedures.
  • Based on the information from other inspections, the national competent authority will prioritise the inspections in its national programme and will use the information for the preparation of an appropriate scope for the national inspection.

4.2 Role of the supervisory authority (Summary)

  • The concept of the supervisory authority applies only in relation to centrally authorised products
  • According to Article 18 of Regulation (EC) 726/2004, the supervisory authority for the conduct of pharmacovigilance inspections shall be the competent authority of the Member State in which the pharmacovigilance system master file is located
  • The supervisory authorities for pharmacovigilance are responsible for verifying on behalf of the Union that the marketing authorisation holder for the medicinal product satisfies the pharmacovigilance requirements laid down in Directive 2001/83/EC and Regulation 726/2004/EC
  • Where the sites selected to be inspected are located outside the EU, the same supervisory authority as above will be responsible for the inspection on behalf of the Union
  • Where relevant or on request, and in particular for product-specific issues, the inspection may be conducted or assisted by inspector(s) from the Rapporteur or Co-Rapporteur Member State and/or expert(s) from the Rapporteur or Co-Rapporteur Member State or from other Member States as appropriate

4. Role of the Member States

4.1 General considerations (summary)
  • Member States should establish the legal and administrative framework within which pharmacovigilance inspections operate, including the definition of the rights of inspectors for inspecting pharmacovigilance sites and access to pharmacovigilance data
  • Member States should provide sufficient resources and appoint adequately qualified inspectors to ensure effective determination of compliance with good pharmacovigilance practice
  • The inspector(s) appointed may be accompanied, when needed, by expert(s) on relevant areas
  • A Member State may also request assistance from another Member State, in which case, access to the inspection sites and data by the Member State providing assistance is desirable
  • A common repository, accessible to all Member States, the Agency and the Commission, should be created to facilitate this information sharing on pharmacovigilance inspections

3. Role of the European Commission

  • For medicinal products authorised under Regulation (EC) No 726/2004, the European Commission may request at any point in time the Agency to coordinate the conduct of a pharmacovigilance inspection if public health information in the possession of the Commission so mandates.

2.3 Role of the CHMP

  • The CHMP is responsible for the request of pharmacovigilance inspections in the context of the centralised procedure and for the endorsement of the recommendations made by the PRAC in relation to the outcome of these inspections and their follow-up
  • The CHMP is also responsible for the adoption of the risk-based programme for routine pharmacovigilance inspections outlined in Section III: Inspection planning and Section XIII, 3.3 Role of the European Commission

2.2 Role of the PRAC

  • The PRAC may make recommendations on the need and scope of “for cause” pharmacovigilance inspections related to medicinal products of Union interest
  • The PRAC may review the outcome of pharmacovigilance inspections and assess marketing authorisation holder-related corrective and preventive action plan submission(s) in order to make or endorse further recommendations on actions to be taken and their follow-up
  • The PRAC is also responsible for providing input in the preparation of and agreeing on the risk-based programme for routine pharmacovigilance inspections of marketing authorisation holders with centrally authorised products outlined in Section III: Inspection planning and Section XIII, 3.3 Role of the European Commission