Commission Implementing Regulation (EU) 2021/1281 of 2 August 2021 laying down rules for the application of Regulation (EU) 2019/6 of the European Parliament and of the Council as regards good pharmacovigilance practice and on the format, content and summary of the pharmacovigilance system master file for veterinary medicinal products (Text with EEA relevance)

THE EUROPEAN COMMISSION,

Having regard to the Treaty on the Functioning of the European Union,

Having regard to Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 laying down Community Regulation on veterinary medicinal products and repealing Directive 2001/82/EC (1), and in particular Article 77(6) thereof,

Whereas:

(1) Good pharmacovigilance practice should cover all activities across the full life-cycle management of veterinary medicinal products in relation to safety authorised in accordance with Article 5 of Regulation (EU) 2019/6 or registered in accordance with Article 86 of that Regulation. Non-compliance with pharmacovigilance obligations could have a potentially serious impact on public and animal health and on the environment.

(2) Marketing authorisation holders should respect good pharmacovigilance practice by implementing a robust and efficient pharmacovigilance system, supported by a quality management system covering all pharmacovigilance activities, including a risk management system covering all procedures and processes necessary to optimise safe use of their veterinary medicinal products. The quality management system should be updated regularly and checked by audits at risk-based intervals, and should include provisions to identify corrective and preventive actions and manage and document corresponding changes to those actions.

(3) In order to facilitate the enforcement of pharmacovigilance obligations, the marketing authorisation holder should retain full responsibility for all pharmacovigilance obligations subcontracted to third parties.

(4) As an important part of a marketing authorisation holder’s quality management system, all information on pharmacovigilance data, including standard procedures, should be saved and preserved in a document management system. The document management system should include a record management system to process safety data.

(5) Adverse event reporting remains the primary information source for post-authorisation safety monitoring and provides most of the data for the evaluation of the benefit-risk balance of a product. Marketing authorisation holders should, within 30 days, record all adverse event reports collected for all their veterinary medicinal products in the Union pharmacovigilance database in order to enable analysis of information received over the full life-cycle of a product.

(6) Standard terminology in the field of medical science should be used in harmonising the exchange of pharmacovigilance information to improve consistency of data related to adverse event reporting.

(7) The calculation of incidence of adverse events should allow for the comparison of different products, product groups or different time periods for the same product.

(8) The signal management process should enable continuous monitoring of the benefit-risk balance of a veterinary medicinal product. It should therefore be a core element of the pharmacovigilance system, allowing appropriate measures to be taken, in accordance with Article 77(4) of Regulation (EU) 2019/6.

(9) Communication of information about the safe and effective use of veterinary medicinal products should support appropriate use and should be considered throughout the risk management process.

(10) The pharmacovigilance system master file should contain all relevant information and documents concerning pharmacovigilance activities, including information on tasks that have been subcontracted to third parties. That information should contribute to the appropriate planning and conduct of audits by marketing authorisation holders and the supervision of pharmacovigilance activities by the qualified person responsible for pharmacovigilance. Furthermore, that information should enable competent authorities to verify compliance concerning all aspects of the system.

(11) Marketing authorisation holders should ensure that they and any third party carrying out pharmacovigilance activities in relation to their veterinary medicinal products make the necessary preparations in order to facilitate controls or inspections by the national competent authorities or the European Medicines Agency.

(12) This Regulation should apply from 28 January 2022 in accordance with Article 153(1) of Regulation (EU) 2019/6.

(13) The measures provided for in this Decision are in accordance with the opinion of the Standing Committee on Veterinary Medicinal Products,

HAS ADOPTED THIS REGULATION:

CHAPTER 1

GENERAL PROVISIONS AND PHARMACOVIGILANCE SYSTEM

Article 1

Definitions

For the purposes of this Regulation, the following definitions shall apply:

(a) ‘quality management system’ means a formalised system that provides for comprehensive processes, procedures, and responsibilities for achieving quality policies and objectives to coordinate and direct an organisation’s activities and improve its effectiveness and efficiency in this regard on a continuous basis;

(b) ‘performance indicator’ means an item of information collected at regular intervals to monitor the performance of a system;

(c) ‘signal’ means information that arises from one or multiple sources, including observations and experiments, which suggests a potentially new causal association, or a new aspect of a known causal association between an intervention and an adverse event or a set of related adverse events, that is judged likely to justify further investigation of possible causality.

Article 2

Pharmacovigilance system

(a) is fully functional;

(b) is covered by a comprehensive quality management system as provided for in Articles 4 to 9 of this Regulation;

(c) includes a risk management system covering all procedures and processes necessary to optimise safe use and monitor benefit-risk balance of their veterinary medicinal products;

(d) sets out clearly the roles, responsibilities and required tasks for all parties involved in operating the system;

(e) provides for proper control over the system and ensures that, when needed, the necessary changes to the system to improve its operation can be carried out;

(f) is clearly and unambiguously documented in the pharmacovigilance system master file.

Article 3

Qualified person responsible for pharmacovigilance

CHAPTER 2

QUALITY MANAGEMENT SYSTEM

Article 4

Quality management system for pharmacovigilance

(a) initial recording of any suspected adverse event;

(b) collection of additional data;

(c) collation of reports of suspected adverse events and additional data;

(d) data handling other than mentioned in points (a) to (c);

(e) evaluation of data;

(f) monitoring of quality, integrity and completeness of all information registered in the pharmacovigilance system including information reported to the Union pharmacovigilance database and management of duplicates;

(g) recording of any adverse event in the Union pharmacovigilance database;

(h) archiving of all relevant documents.

(a) quality planning: establishing structures, integrated planning and consistent processes;

(b) quality adherence: carrying out tasks and responsibilities in accordance with quality requirements;

(c) quality control and assurance: monitoring and evaluating how effectively the structures and processes have been established and how effectively the processes are implemented;

(d) quality improvements: correcting and improving the structures and processes where necessary.

Article 5

Document management system

Article 6

Training

Article 7

Performance indicators

Marketing authorisation holders shall use relevant performance indicators to continuously monitor the performance of pharmacovigilance activities and the outcome of risk minimisation measures. They shall keep a list of those performance indicators including the reason why they have been chosen and a description on how to use them in Annex IV, point (iii) to the pharmacovigilance system master file.

Article 8

Audits

Article 9

Corrective and preventive action and change management

CHAPTER 3

RECORD MANAGEMENT SYSTEM, DATA COLLECTION AND MONITORING

Article 10

Record management system

(a) type of record management system used for adverse event reports, including the name of the database used, if applicable;