Pharmacovigilance system: questions and answers

This page lists questions that marketing-authorisation holders (MAHs) may have on the pharmacovigilance system.

Find on this page an overview of the European Medicines Agency's position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. 

Revised topics are marked 'New' or 'Rev.' upon publication.

A PDF version of the entire post-authorisation guidance is available:

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

Reference Number: EMEA-H-19984/03 Rev. 113

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure: document with tracked changes

Reference Number: EMEA-H-19984/03 Rev. 113

These questions and answers have been produced for guidance only and should be read in conjunction with the rules governing medicinal products in the European Union, volume 2, notice to applicants.

MAHs must in all cases comply with the requirements of Community legislation. Provisions that extend to Iceland, Liechtenstein and Norway by virtue of the European Economic Area agreement are outlined in the relevant sections of the text.

1. Requirements regarding the summary of the pharmacovigilance system - Rev. January 2016

Applicants for marketing authorisation are required to provide a summary of their pharmacovigilance system, in accordance with Article 8(3)(ia) of Directive 2001/83/EC, which they will introduce once the authorisation is granted .

The requirement for the summary of the pharmacovigilance system was introduced by the new pharmacovigilance legislation (Directive 2010/84/EU amending, as regards pharmacovigilance, Directive 2001/83/EC).

The summary of the pharmacovigilance system should be provided in Module 1.8.1 of the application for marketing authorisation and includes the following elements:

• proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance,
• the Member States in which the qualified person resides and carries out his/her tasks,
• the contact details of the qualified person,
• a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC,
• a reference to the location where the pharmacovigilance system master file (PSMF) for the medicinal product is kept.

The MAH may combine this information in one single statement using the required statement as per Article 8(3)(ia) of Directive 2001/83/EC regarding the obligation to have the necessary means to fulfil the tasks and responsibilities listed in Title IX (Pharmacovigilance). Such statement should be signed by an individual who can act on behalf of the legal entity of the applicant/MAH and by the qualified person responsible for pharmacovigilance (QPPV). The title, role and responsibility of each individual signing the statement should be clearly specified in the document.

The summary of the pharmacovigilance system is specific to each application/marketing authorisation as per the legislation and therefore should be signed by the relevant applicant/MAH.The requirement for the summary of the pharmacovigilance system is the same for any marketing authorisation application, independent of the legal basis for the application.

References

• Directive 2001/83/EC
• Directive 2010/84/EU
• Commission implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council
• Questions and answers on practical transitional measures for the implementation of the pharmacovigilance legislation
• Guideline on good pharmacovigilance practices - Module I – Pharmacovigilance systems and their quality systems (EMA/541760/2011)
• Guideline on good pharmacovigilance practices - Module II – Pharmacovigilance system master file(EMA/816573/2011)

2. Requirements regarding the pharmacovigilance system and pharmacovigilance system master file

The MAH has to operate a pharmacovigilance system for the fulfilment of his pharmacovigilance tasks.

The pharmacovigilance system master file (PSMF) is a detailed description of the pharmacovigilance system used by the MAH with respect to one or more authorised medicinal products.

The PSMF is not part of the marketing authorisation (MA) dossier and is maintained independently from the MA. It should be permanently available for inspection and should be provided within 7 days to the Competent Authorities if requested. The PSMF must 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 QPPV operates. The QPPV has to both reside and operate in the Union.

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

The PSMF has to 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 pharmacovigilance system will have to be in place and functioning at the time of granting of the MA and placing of the product on the market.

References

• Directive 2001/83/EC
• Guideline on good pharmacovigilance practices - Module II – Pharmacovigilance system master file(EMA/816573/2011)

3. Subcontracting pharmacovigilance activities

The MAH may subcontract certain activities of the pharmacovigilance system to third parties. It shall nevertheless retain full responsibility for the completeness and accuracy of the pharmacovigilance system master file (PSMF).

The MAH will have to draw up a list of its existing subcontracts between himself and the third parties, specifying the product(s) and territory(ies) concerned.

When delegating any activities concerning the pharmacovigilance system and its master file, the MAH retains ultimate responsibility for the pharmacovigilance system, submission of information about the PSMF location, maintenance of the PSMF and its provision to competent authorities upon request. Detailed written agreements describing the roles and responsibilities for PSMF content, submissions and management, as well as to govern the conduct of pharmacovigilance in accordance with the legal requirements, should be in place.

For more guidance on the requirements for pharmacovigilance system and PSMF, please refer to the relevant Good Pharmacovigilance Practice (GVP) Modules.

References

• Guideline on good pharmacovigilance practices: Module I – Pharmacovigilance systems and their quality systems
• Guideline on good pharmacovigilance practices: Module II – Pharmacovigilance system master file (Rev. 2)

4. How to inform the authorities of a change in the summary of the pharmacovigilance system? - Rev. January 2016

As of 1 February 2016, changes to the summary of the pharmacovigilance system – changes in QPPV (including contact details) and/or changes in the Pharmacovigilance Master File (PSMF) location are to be notified to the authorities through the Art 57 database only without the need for any further variation. From that date MAHs are not required to notify EMA or national competent authorities (as applicable) of changes to the QPPV or PSMF data by submitting a type IA_IN variation.

Upon a change in the QPPV or location of the PMSF, the Art 57 database should be updated by the MAH immediately to allow continuous supervision by the Competent Authorities.

References

• News item: Regulatory information – Green light for reliance on Article 57 database for key pharmacovigilance information on medicines for human use in Europe
• Art. 57 Reporting requirements for Marketing Authorisation Holders
• Detailed Guidance on electronic submission of information on medicines
• Volume 2C of the Rules Governing Medicinal Products in the European Union - Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures

5. Is it mandatory to enter and maintain the location of the Pharmacovigilance System Master File in the XEVMPD? If so, how do we enter this information in the XEVMPD? NEW January 2016

Please refer to question "Is it mandatory to enter and maintain the Location of the Pharmacovigilance System Master File in the XEVMPD? If so, how do we enter this information in the XEVMPD?" under section 3.4.4 What are the requirements for my pharmacovigilance system? in the pre-authorisation guidance.

6. Is the information on the Deputy QPPV required as part of the summary of the pharmacovigilance system? Rev. January 2016

Please refer to question "Is the information on the Deputy QPPV required as part of the summary of the pharmacovigilance system?" under section 3.4.4 What are the requirements for my pharmacovigilance system? in the pre-authorisation guidance.

7. Is there a PSMF template? NEW January 2016

Please refer to question "Is there a PSMF template?" under section 3.4.3 What are the requirements for my pharmacovigilance system? in the pre-authorisation guidance.

8. Pharmacovigilance System Master File location: can the server of the Pharmacovigilance System Master File be physically located and administered outside EU if it is validated and operational/accessible 24/7 for EU markets and EU QPPV? NEW Jan 2016

Please refer to question “Pharmacovigilance System Master File location: can the server of the Pharmacovigilance System Master File be physically located and administered outside EU if it is validated and operational/accessible 24/7 for EU markets and EU QPPV?” under section 3.4.3 What are the requirements for my pharmacovigilance system? in the pre-authorisation guidance.

9. What information will be made public on the EU web-portal regarding pharmacovigilance contact details and PSMF locations? Will details of the QPPV be made public? NEW January 2016

Please refer to question "What information will be made public on the EU web-portal regarding pharmacovigilance contact details and PSMF locations? Will details of the QPPV be made public??" under section 3.4.3 What are the requirements for my pharmacovigilance system? in the pre-authorisation guidance.