(fra kommisjonsforordningen)

(1) Commission Implementing Regulation (EU) No 520/2012 (3) sets out certain implementing measures for the performance of pharmacovigilance activities. In light of practical experience in applying that Implementing Regulation, technical and scientific progress, and international harmonisation in pharmacovigilance, it is appropriate to review it, while guaranteeing the same level of public health protection.

(2) Implementing Regulation (EU) No 520/2012 sets out, among other things, the content of the pharmacovigilance system master file. To avoid unnecessary administrative burden for applicants and competent authorities, only significant deviations from the pharmacovigilance procedures, their impact and their management should be documented in the pharmacovigilance system master file until resolved.

(3) Marketing authorisation holders may subcontract certain activities of the pharmacovigilance system to third parties, for example to specialised service providers. Where the pharmacovigilance tasks have been subcontracted by the marketing authorisation holder to a third party (or by this third party to another third party), delegation arrangements, each party’s responsibilities, and audit and inspection arrangements should be clearly documented. Third parties should agree to be audited by or on behalf of marketing authorisation holders and inspected by the competent authorities in order to guarantee and verify compliance concerning all aspects of the pharmacovigilance system.

(4) Marketing authorisation holders are to establish quality systems for the performance of pharmacovigilance activities pursuant to Article 8(1) of Implementing Regulation (EU) No 520/2012. In accordance with Article 13 of that Regulation, those quality systems are to be audited. In order to ensure better efficiency of audits, the content of those audits should be further defined in this Regulation. The third party subcontracted to carry out pharmacovigilance tasks in whole or in part on behalf of or in conjunction with marketing authorisation holders should be audited by or on behalf of the marketing authorisation holder and may be inspected by the competent authorities, irrespective of whether or not this obligation is mentioned in the subcontract. It is important that subcontractors have clarity about their obligations, which should be set out in the subcontract, but a subcontract’s shortcomings should not affect the performance of audits and inspections.

(5) The Eudravigilance database is the system for managing and analysing information on adverse reactions to medicines that have been authorised or are being studied in clinical trials. The European Medicines Agency (‘the Agency’) and national competent authorities continuously monitor the data in the Eudravigilance database. The database is also accessible to marketing authorisation holders to the extent necessary for them to fulfil their pharmacovigilance obligations. Based on the experience acquired from marketing authorisation holders’ monitoring of the data in the Eudravigilance database, the requirements for marketing authorisation holders should be clarified, including the requirements for signal validation and subsequent notification to the Agency and national competent authorities.

(6) In order to facilitate the interoperability of systems, avoid the duplication of encoding activities concerning the same information and allow for an easier exchange of information, this Regulation takes into account developments in international standards used by marketing authorisation holders, national competent authorities and the Agency for the performance of pharmacovigilance activities, as well as the need for certain updates to terminology.

(7) Suspected adverse reactions to a medicinal product are reported to the Eudravigilance database by means of individual case safety reports. The reports should be as complete as possible, but in order to ensure some standardisation of reports, minimum reporting requirements should apply in all cases.

(8) For better literature referencing in individual case safety reports, Member States and marketing authorisation holders should provide the digital object identifier (DOI), if available, when reporting suspected adverse reactions.

(9) In order to clarify and strengthen the content of the periodic safety update report, that report should include updates on the implementation of risk minimisation measures.

(10) If national competent authorities, the Agency or the Commission have concerns about the safety of a medicinal product, they may oblige a marketing authorisation holder to initiate, manage and finance non-interventional post-authorisation safety studies. In order for them to be transparent, the marketing authorisation holder should put such studies in the electronic post-authorisation study register maintained by the Agency.

(11) Implementing Regulation (EU) No 520/2012 should therefore be amended accordingly.

(12) The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee for Medicinal Products for Human Use,