On 23 July 2025, the European Commission published Implementing Regulation (EU) 2025/1466, amending Regulation (EU) No 520/2012. This highly anticipated update brings substantial changes to pharmacovigilance (PV) obligations for Marketing Authorisation Holders (MAHs) across the European Union.
The new regulation strengthens the regulatory framework and places greater emphasis on global system oversight, auditability, third-party control, and transparency in post-authorisation safety studies (PASS). The regulation is fully applicable from 12 February 2026, while some sections came into force already in August 2025.
What are the key changes in EU Regulation 2025/1466?
1. Global PV system structure and PSMF requirements
MAHs must clearly define and document their global pharmacovigilance system – including roles, responsibilities, and site-specific functions. This applies to all locations involved in safety data collection, signal management, PSUR/RMP preparation, and case handling. Notably, only significant deviations from standard procedures now need to be recorded in the Pharmacovigilance System Master File (PSMF), reducing administrative burden while improving focus on critical changes.
2. Third-party oversight and subcontractor audits
The regulation reinforces the importance of contractual clarity. MAHs must ensure all agreements with third parties – including subcontractors – clearly outline roles, responsibilities, safety data flow, and audit rights. Even entities that do not have a direct agreement with the MAH must be auditable and further subcontracting should always be approved by the MAH. This ensures full oversight of outsourced pharmacovigilance activities and will require updates in standard operating procedures (SOPs) and contractual agreements.
3. Risk-based audit strategy
All MAHs must implement an independent, risk-based audit strategy that covers the entire pharmacovigilance system. These audits must be documented, repeatable, and capable of identifying non-compliance. The new regulation aims to elevate the quality assurance of PV systems, independence of the auditors and ensure continuous process improvement.
4. Clarification of roles in signal validation
Signal validation responsibilities in EudraVigilance are now clearly assigned to EMA and national competent authorities (NCAs). While MAHs are still encouraged to monitor EudraVigilance data, they are no longer expected to lead the validation process.
The update also clarifies that all MAHs with products approved in the EEA shall monitor the EudraVigilance database as an additional source for safety information to support their signal detection and enhancement processes.
The MAHs with EU products authorised in Northern Ireland should also monitor EudraVigilance, even if they are not authorised in an EU/EEA Member State.
The clarification from EMA aligns expectations and reduces ambiguity in roles.
5. PASS study transparency
Mandatory Post-Authorisation Safety Studies (PASS) must be registered in the ENCePP registry before any data collection begins. In addition, MAHs must ensure public availability of the study protocol and final study report, promoting transparency and trust in real-world evidence generation.
Why does this matter for Marketing Authorisation Holders?
Regulation 2025/1466 marks a shift toward more structured and transparent pharmacovigilance operations. MAHs must proactively adapt their PV systems to meet these new requirements. Delayed action could result in audit findings, compliance risks, and regulatory delays.
Now is the time to:
- Review your global PV system description and PSMF documentation
- Re-evaluate third-party contracts and audit clauses
- Update SOPs and internal processes
- Plan and document risk-based audits
- Ensure timely PASS registrations
As a trusted pharmacovigilance and regulatory partner, Medfiles offers end-to-end support to ensure you remain compliant with evolving EU regulations. Our experienced PV and regulatory professionals are ready to help you manage this change smoothly and compliantly.
Author: Saara Mikkola, Head of Operations, Pharmacovigilance, EU QPPV
Saara Mikkola joined Medfiles Pharmacovigilance team in 2020 as a Drug Safety Expert, and in 2022 she was promoted to Safety Manager and later to Head of Operations, Pharmacovigilance. She works as an EU QPPV for Medfiles and has her focus on post-market pharmacovigilance services.
Saara has a master’s degree in pharmacy and graduated from the University of Helsinki, Finland, in 2012. She has worked within the pharmaceutical industry for over 10 years with her focus on pharmacovigilance. Saara has gained her expertise through diverse pharmacovigilance tasks and responsibilities. She is well-versed in the operational aspects of pharmacovigilance, including case processing, quality management, compliance with regulatory requirements (EU regulation), and maintaining pharmacovigilance systems.
She is adept at working in cross-functional teams, collaborating with different stakeholders, and adapting to the ever-evolving pharmacovigilance landscape and technologies.
Author: Arda Sanaktekin, Drug Safety Expert
Arda Sanaktekin joined the Medfiles Pharmacovigilance team in August 2025 as a Drug Safety Expert. She holds a pharmacy degree and an MSc in Toxicology. Arda has gained extensive experience in pharmacovigilance, medical information and quality oversight within international companies. Her background enables her to approach drug safety from both a scientific and operational perspective, ensuring that regulatory requirements are translated into practical, workable processes.
At Medfiles, Arda is responsible for a range of pharmacovigilance activities, including global literature review, regulatory intelligence and vendor management. She is committed to delivering high-quality, reliable support that strengthens compliance and ensures patient safety across diverse product portfolios.
