Pharmacovigilance plays a crucial role in ensuring the continued safety and effectiveness of medicines.  It involves the monitoring and evaluation of any adverse reactions associated with medicinal products. In the European Union, pharmacovigilance is governed by a comprehensive regulatory framework, with the last significant set piece being a 2012 Implementing Regulation. On 22 July 2025, the European Commission adopted a new regulation, Commission Implementing Regulation (EU) 2025/1466 of 22 July 2025 amending Implementing Regulation (EU) No 520/2012 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 (the“2025 Regulation”), which is the first substantive amendment to the pharmacovigilance framework since 2012.

The 2025 Regulation introduces some key changes to the existing legislative framework to streamline administrative processes, align EU pharmacovigilance practices with global standards and improve the framework overall, reflecting scientific and sector-specific developments since the introduction of the initial Regulation. Certain parts of the new framework, including minor amendments to the concept of signal monitoring and the use of EudraVigilance data, came into effect on 12 August 2025. The remaining updates will apply from 12 February 2026.

What does the 2025 Regulation change?

Below are some of the key points which marketing authorisation holders (“MAHs”) should be aware of:

Master file: Under the existing legislative regime MAHs must maintain a Pharmacovigilance System Master File, which documents the structure and operation of a MAH’s pharmacovigilance system.  MAHs are currently required to record “any” deviation from established pharmacovigilance procedures until the issue is resolved.  From February 2026, under the revised framework, MAHs will only be required to document “major or critical deviations” from procedure.  This arguably reduces the administrative burden on MAHs and allows for a focus on significant compliance issues, while maintaining regulatory oversight.

Subcontracting: The 2025 Regulation paves the way for greater clarity and supervision when subcontracting pharmacovigilance activities.  Any subcontracts concluded by MAHs with third parties to conduct pharmacovigilance activities must clearly set out:

• The third party’s roles and responsibilities;
• The third party’s obligation to exchange safety data with the MAH and the method for doing so;
• Arrangements for inspection and auditing of the third party; and
• The obligation on the third party to agree to be audited by the MAH and inspected by competent authorities.

The 2025 Regulation clarifies that third parties cannot subcontract any pharmacovigilance task assigned to them by the MAH to another third party without the MAH’s written consent.

Audits: The 2025 Regulation widens auditing requirements and introduces a clear framework for audits and inspections.  The 2025 Regulation:

1. Increases the scope of audits, which now explicitly cover all pharmacovigilance activities for a defined period; and
2. Further provides for regular audits on third parties subcontracted to conduct pharmacovigilance tasks.  “Regular” is not defined by the 2025 Regulation nor the 2001 Directive.

The 2025 Regulation requires that audits verify conformity with the policies, processes and procedures of the quality system, and must be independent.

EudraVigilance database monitoring: The EudraVigilance database is a centralised European database managed by the European Medicines Agency (“EMA”) for reports of suspected adverse reactions to medicines that are authorised or undergoing clinical trials in the EEA.  This policy is based on a proactive approach to disclosing information to expand the pool of data available to conduct safety assessments and research.  The 2025 Regulation has amended this framework as follows:

• As of 12 August 2025, the responsibility for continuous risk-based monitoring of the EudraVigilance Database has shifted.  The continuous monitoring of the EudraVigilance Database is now the responsibility of national competent authorities and the EMA, which must analyse the database along with other relevant data sources to detect safety signals and monitor the safety of medicine.
• The identification of changed and new risks by these bodies has been expanded. When monitoring data in the EudraVigilance database, national competent authorities and the EMA were under an obligation to consider only signals related to an “adverse reaction”.  This requirement has been expanded under the 2025 Regulation so that these regulatory bodies will also have to consider “suspected” adverse reactions from February 2026.
• Previously, MAHs were required to submit validated signals to the EMA via standalone notification forms.  However, from now on signals must be handled according to the MAH’s own signal management process in line with Good Pharmacovigilance Practices and MAHs must revise their internal procedures to ensure that EudraVigilance data is monitored in parallel with other relevant sources.

Impact

The recent updates to the framework maintain the core principles of the existing regime, while also introducing some meaningful changes to the sector.  This update brings what will be a welcome reduction in administrative burden on MAHs, greater transparency and a potential for improving the safety of medicines.  It is important, however, for stakeholders to remain vigilant and fully inform themselves about any additional obligations which may apply to them, including audit and reporting requirements, to ensure continued compliance with regulatory responsibilities.

While a small number of these changes are already in force, the majority of the amendments will become live in February 2026.  This gives MAHs the opportunity to revise their policies and procedures in the interim to ensure continued compliance with the pharmacovigilance framework.

For further information, please contact the Life Sciences Group.