CHAPTER I

Pharmacovigilance system master file

Structure of the pharmacovigilance system master file
Article 1
1
The information in the pharmacovigilance system master file shall be accurate and reflect the pharmacovigilance system in place.
2
The marketing authorisation holder may, where appropriate, use separate pharmacovigilance systems for different categories of medicinal products. Each such system shall be described in a separate pharmacovigilance system master file.
All medicinal products for which the marketing authorisation holder obtained a marketing authorisation in accordance with Directive 2001/83/EC or Regulation (EC) No 726/2004 shall be covered by a pharmacovigilance system master file.

Content of the pharmacovigilance system master file
Article 2
The pharmacovigilance system master file shall contain at least all of the following elements:
1. the following information relating to the qualified person responsible for pharmacovigilance:
  1. a description of the responsibilities demonstrating that the qualified person responsible for pharmacovigilance has sufficient authority over the pharmacovigilance system in order to promote, maintain and improve compliance with pharmacovigilance tasks and responsibilities;
  2. a summary curriculum vitae of the qualified person responsible for pharmacovigilance, including proof of registration with the Eudravigilance database;
  3. contact details of the qualified person responsible for pharmacovigilance;
  4. details of back-up arrangements to apply in the absence of the qualified person responsible for pharmacovigilance;
  5. responsibilities of the contact person for pharmacovigilance issues where such a person has been nominated at national level in accordance with Article 104(4) of Directive 2001/83/EC, including contact details;
2. a description of the organisational structure of the marketing authorisation holder, including the list of the site(s) where the following pharmacovigilance activities are undertaken: individual case safety report collection, evaluation, safety database case entry, periodic safety update report production, signal detection and analysis, risk management plan management, pre- and post-authorisation study management, and management of safety variations to the terms of a marketing authorisation;
3. a description of the location of, functionality of and operational responsibility for computerised systems and databases used to receive, collate, record and report safety information and an assessment of their fitness for purpose;
4. a description of data handling and recording and of the process used for each of the following pharmacovigilance activities:
  1. the continuous monitoring of the risk-benefit balance of the medicinal product(s), the result of that monitoring and the decision-making process for taking appropriate measures;
  2. operation of the risk management system(s) and of the monitoring of the outcome of risk minimisation measures;
  3. collection, assessment and reporting of individual case safety reports;
  4. drafting and submission of periodic safety update reports;
  5. procedures for communicating safety concerns and safety variations to the summary of product characteristics and package leaflet to healthcare professionals and the general public;
5. a description of the quality system for the performance of pharmacovigilance activities, including all of the following elements:
  1. a description of the management of human resources referred to in Article 10 containing the following elements: a description of the organisational structure for the performance of pharmacovigilance activities with a reference to the location of qualification records of the personnel; a summary description of the training concept, including a reference to the location of training files; instructions on critical processes;
  2. a description of the record management system referred to in Article 12, including the location of the documents used for pharmacovigilance activities;
  3. a description of the system for monitoring the performance of the pharmacovigilance system and for the compliance with Article 11;
6. where applicable, a description of the activities and/or services subcontracted by the marketing authorisation holder in accordance with Article 6(1).

Content of the Annex to the pharmacovigilance system master file
Article 3
The pharmacovigilance system master file shall have an Annex containing the following documents:
1. a list of medicinal products covered by the pharmacovigilance system master file, including the name of the medicinal product, the international non-proprietary name (INN) of the active substance(s), and the Member State(s) in which the authorisation is valid;
2. a list of written policies and procedures for the purpose of complying with Article 11(1);
3. the list of subcontracts referred to in Article 6(2);
4. a list of the tasks that have been delegated by the qualified person for pharmacovigilance;
5. a list of all scheduled and completed audits;
6. where applicable, a list of the performance indicators referred to in Article 9;
7. where applicable, a list of other pharmacovigilance system master files held by the same marketing authorisation holder;
8. a logbook containing the information referred to in Article 5(4).

Maintenance
Article 4
1
The marketing authorisation holder shall keep the pharmacovigilance system master file up to date and, where necessary, revise it to take account of experience gained, of technical and scientific progress and of amendments to Directive 2001/83/EC and Regulation (EC) No 726/2004.
2
The pharmacovigilance system master file and its Annex shall be subject to version control and shall indicate the date when it was last updated by the marketing authorisation holder.
3
Any deviations from the pharmacovigilance procedures, their impact and their management shall be documented in the pharmacovigilance system master file until resolved.
4
Without prejudice to the requirements set out in 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
, the marketing authorisation holder shall notify immediately the Agency of any change in the location of the pharmacovigilance system master file or changes to the contact details and name of the qualified person responsible for pharmacovigilance. The Agency shall update 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 accordingly.

Form of the documents contained in the pharmacovigilance system master file
Article 5
1
Pharmacovigilance system master file documents shall be complete and legible. Where appropriate, information may be provided in the form of charts or flow diagrams. All documents shall be indexed and archived so as to ensure their accurate and ready retrieval throughout the period for record-keeping.
2
The particulars and documents of the pharmacovigilance system master file may be presented in modules in accordance with the system delineated in detail in the guidance on good pharmacovigilance practices.
3
The pharmacovigilance system master file may be stored in electronic form provided that the media used for storage remain readable over time and a clearly arranged printed copy can be made available for audits and inspections.
4
The marketing authorisation holder shall record in the logbook referred to in point 8 of Article 3 any alteration of the content of the pharmacovigilance system master file made within the last five years, with the exception of the information referred to in point 1(b) to (e) of Article 2 and in Article 3. The marketing authorisation holder shall indicate in the logbook the date, the person responsible for the alteration and, where appropriate, the reason for the alteration.

Subcontracting
Article 6
1
The marketing authorisation holder 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.
2
The marketing authorisation holder shall draw up a list of its existing subcontracts between it and the third parties referred to in paragraph 1, specifying the product(s) and territory(ies) concerned.

Availability and location of the pharmacovigilance system master file
Article 7
1
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.
2
The marketing authorisation holder shall ensure that the qualified person for pharmacovigilance has permanent access to the pharmacovigilance system master file.
3
The pharmacovigilance system master file shall be permanently and immediately available for inspection at the site where it is kept.
Where the pharmacovigilance system master file is kept in electronic form in accordance with Article 5(3), it is sufficient for the purposes of this Article that the data stored in electronic form is directly available at the site where the pharmacovigilance system master file is kept.
4
For the purposes of Article 23(4) of Directive 2001/83/EC, the national competent authority may limit its request to specific parts or modules of the pharmacovigilance system master file and the marketing authorisation holder shall bear the costs of submitting the copy of the pharmacovigilance system master file.
5
The national competent authority and the Agency may request the marketing authorisation holder to submit a copy of the logbook referred to in point 8 of Article 3 at regular intervals.
OJ L 334, 24.11.2008, p. 7.
Regulation revoked in part (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), reg. 1, Sch. 9 para. 1(t) (subject to transitional provisions in S.I. 2012/1916, Sch. 33A); 2020 c. 1, Sch. 5 para. 1(1)