On 22 July 2025, the European Commission published Implementing Regulation (EU) 2025/1466, updating and amending Implementing Regulation (EU) No 520/2012 on the performance of pharmacovigilance activities.

This update aligns with Regulation (EC) No 726/2004 and Directive 2001/83/EC and introduces significant changes for marketing authorisation holders (MAHs), particularly in signal management, subcontracting, reporting requirements, and audit expectations.

Key Changes for MAHs

Pharmacovigilance System Master File (PSMF)

● Only significant deviations from pharmacovigilance procedures and should be documented until resolved.

● This change aims to reduce unnecessary administrative burden for both MAHs and competent authorities.

Subcontracting of Pharmacovigilance Activities

● Stricter requirements for managing third-party relationships:

a) All subcontracting arrangements must clearly define roles, responsibilities, and data exchange processes.

b) Third parties must agree to audits by MAHs and inspections by competent authorities.

c) Further subcontracting requires written approval from the MAH.

● This is one of the most significant areas of change and will require updates to contracts, SOPs, and governance structures.

Signal Management

● The Eudravigilance database becomes central to signal detection and signal evaluation.

● The previous signal pilot has ended; MAHs are now fully responsible for monitoring Eudravigilance alongside other data sources.

● SOPs and signal detection templates will need updating to include Eudravigilance as a mandatory source.

Individual Case Safety Reports (ICSRs) & Literature Reports

● ICSR submissions must include:

a) Should be as complete as possible and include at least one identifiable reporter, one identifiable patient, and at least one suspected adverse reaction.

b) Ensure processes to avoid duplicate submissions

● Literature reports should include the Digital Object Identifier (DOI) where available and follow Vancouver referencing style.

Post-Authorisation Safety Studies (PASS)

● MAHs must:

a) Enter the study protocol into the EU PAS Register before data collection begins.

b) Submit the abstract of the final study report within one month of finalisation.

c) Include all key study milestones in the register.

Periodic Safety Update Reports (PSURs)

● PSURs should include:

a) Implementation of risk minimisation measures (RMMs).

b) Results of RMM effectiveness assessments.

Audits

● Confirmation of the need for risk-based audits of the quality system at regular intervals for compliance and effectiveness.

● Should cover all aspects of the pharmacovigilance system.

● Audits must be conducted by independent individuals with no direct involvement in the areas being audited.

Standardised Terminology and Data Standards

● To improve interoperability and data exchange, the regulation mandates the use of internationally recognised terminology and standards, including:

a) MedDRA

b) European Pharmacopoeia Standard Terms

c) IDMP Standards (EN ISO 11615, 11616, 11238, 11239, 11240)

d) XEVMPD for electronic submissions.

 

What This Means for MAHs

Implementing Regulation 2025/1466 introduces higher compliance expectations and requires updates to governance, processes, and systems. MAHs should:

● Review and update SOPs for pharmacovigilance, literature screening, PASS, PSURs, audits, and signal detection.

● Revise subcontracting agreements to ensure audit and inspection rights are covered.

● Train internal teams on reporting requirements and data standards.

● Ensure trackers and monitoring systems implemented for PASS and this translates to the PSUR.

● Strengthen oversight of third parties to avoid compliance risks.

 

How We Can Help

At Sagittal Pharma Consulting, we specialise in pharmacovigilance compliance and can support your organisation in adapting to Implementing Regulation (EU) 2025/1466. Our services include:

● SOP Reviews & Updates – Aligning your procedures with the new regulatory requirements.

● Third-Party Contract Reviews – Ensuring subcontracting agreements are compliant and audit-ready.

● Signal Management Training – Helping your teams navigate Eudravigilance and integrate it into detection and assessment workflows.

● Audit Services – Conducting risk-based pharmacovigilance audits to identify and address compliance gaps.

● Process Optimisation – Supporting implementation of effective trackers, governance structures, and reporting systems.

With our expertise, you can confidently navigate the regulatory changes and maintain full compliance.