On 22 July 2025, the European Commission adopted Implementing Regulation (EU) 2025/1466 ("Regulation"), updating the EU pharmacovigilance (or "PV") rules by way of amendments to Implementing Regulation (EU) No 520/2012. The changes aim to clarify and strengthen certain pharmacovigilance obligations (some of which arguably reflect what is already the current practice and expectations of the EU PV inspectors).
The Regulation introduces a number of new compliance expectations and requirements for applicants and marketing authorisation holders ("MAHs"), some of which will start to apply before mid-August.
Pharmacovigilance System Master File Requirements
Only "major or critical" deviations from pharmacovigilance procedures will need to be documented in the pharmacovigilance system master file until resolved. The change is intended to avoid unnecessary administrative burden for applicants, MAHs and the EU competent authorities, as the current regulation requires documentation of "any deviation" from the pharmacovigilance procedures.
Rules on Sub-Contracting
Where a MAH sub-contracts any of its pharmacovigilance obligations to a third party, the Regulation requires that the sub-contract includes:
- Clearly defined roles and responsibilities of third parties;
- Obligation of the third party to exchange safety data with the MAH;
- Arrangements for inspection and auditing of third parties; and
- Obligation of the third party to agree to be audited by or on behalf of the MAH and inspected by competent authorities.
In addition, under the Regulation, third parties cannot subcontract pharmacovigilance tasks without written consent from the MAH. We understand that this change is intended to address common issues identified in PV inspections e.g., inability of EU PV inspectors to inspect all vendors and vendors' vendors; unclear and/or vague definition of each party's PV roles, tasks and responsibilities and shortcomings in communications.
Strengthened Audit Obligations
MAHs are obliged to conduct risk-based audits of their pharmacovigilance systems. The Regulation clarifies the wording of this obligation to be more specific about the content of those audits. The Regulation specifies that the audits "shall individually or taken together, cover all pharmacovigilance activities for a defined period and verify those activities' conformity with the policies, processes and procedures of the quality system."
Eudravigilance Monitoring and Signal Management
The Regulation requires MAHs to not just monitor, but also use the data in the Eudravigilance database, together with data from other available sources. The Regulation also clarifies that only signals related to a "suspected adverse reaction" shall be considered, which is an extension from the current regulation that requires "adverse reactions" to be considered.
Periodic Safety Update Reports
Periodic Safety Update Reports ("PSURs") must include updates on the implementation of risk minimisation measures. PSURs must also include results of assessments of the effectiveness of risk minimisation activities that are relevant to the risk-benefit assessment.
Post-Authorisation Safety Studies
The Regulation adds detail on the reporting process for post-authorisation safety studies (PASS), requiring MAHs to register PASS documents in the electronic post-authorisation study register maintained by the EMA. PASS protocols must be submitted before data collection begins, and the abstract of the final report must be submitted within one month of finalisation.
Reporting Terminology and Standards
To facilitate the interoperability of pharmacovigilance systems, and allow for an easier exchange of information, the Regulation mandates use of certain internationally agreed terminology and standards e.g., the Medical Dictionary for Regulatory Activities and the lists of Standard Terms published by the European Pharmacopoeia Commission.
The amendment is intended to take into account developments in international standards used by MAHs, national competent authorities and the EMA in the performance of pharmacovigilance activities.
Looking forward
The obligation for MAHs to both monitor and use of Eudravigilance content will apply from 12 August 2025 and the remainder of the Regulation will come into force on 12 February 2026.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
