EMA GVP Module VII – Explanatory Note (Rev. 4): Periodic Safety Update Report (PSUR) Single Assessment

Sharan Murugan
8 hours ago
3 min read

The European Medicines Agency (EMA) has issued Revision 4 of the "Explanatory Note to Good Pharmacovigilance Practices (GVP) Module VII – Periodic Safety Update Report" prepared by the Human Medicines Evaluation Division. This revision addresses practical challenges encountered during the PSUR Single Assessment (PSUSA) process, particularly for nationally authorised medicinal products (NAPs), and serves as the basis for the forthcoming update of GVP Module VII.

Purpose of the Explanatory Note

Since the launch of the PSUSA procedure, the assessment of NAPs has presented specific and recurring challenges. This explanatory note aims to:

Clarify expectations for PSUR content and quality
Reduce requests for clarification during assessment
Provide guidance applicable to both NAPs and centrally authorised products (CAPs)
Serve as a transitional document until the full GVP Module VII revision is published

All EU-specific information should be included in the EU regional appendix of the PSUR (GVP Module VII section VII.C.5).

Principles for Benefit-Risk Evaluation

The core purpose of a PSUR is a comprehensive, concise, and critical analysis of the benefit/risk balance of the medicinal product, taking into account new or emerging information in the context of cumulative data.

Key expectations from the Qualified Person responsible for Pharmacovigilance (QPPV):

Ensure PSURs are prepared with a clear, logical flow that facilitates understanding of data, conclusions, and proposed actions
Tailor the level of detail based on the clinical significance of findings
Limit patient-level data in line with GDPR and EUDPR data protection requirements — only data elements listed under Access Level 2A in the EudraVigilance Access Policy should be included

PSURs are not the appropriate mechanism for urgent safety notifications — these should be handled via GVP Module IX (signal management).

Key Content Areas and Recommendations

Actions Taken for Safety Reasons

Significant safety actions taken globally during the reporting interval must be described in sufficient detail, including:

Labelling restrictions or changes
Withdrawal or suspension of a marketing authorisation (MA)
Risk management activities and Direct Healthcare Professional Communications (DHPCs)
Pharmacovigilance inspections prompted by safety concerns

Vague statements (e.g., "interruption of market placement") are not acceptable.

Reference Information and Product Information (PI)

The reference PI must be provided in English
Proposed PI changes should reflect safety-relevant updates only
Any discussion on RSI (Reference Safety Information) impact must be included in the EU regional appendix (section VII.C.5.1)
MAHs must confirm they have assessed the impact of PSUR data on the authorised PI

Patient Exposure

Exposure data should include the number of patients and exposure duration (preferably patient-years)
Discrepancies between PSURs must be explained and justified with adequate detail

Signal Evaluation

Signal assessment should be based on an aggregated cumulative review of all data available to the MAH, evaluating the weight of evidence for or against a causal association.

The signal evaluation section (section 16.2 of the PSUR) must clearly include:

Description and source of the signal
Evaluation background and methodology
Results from cumulative data review
Conclusion — whether the signal is refuted, classified as an identified risk, or a potential risk
Proposed or taken actions

Signals should not be refuted solely because the original reporter did not consider the adverse reaction drug-related. Recognised methodologies such as the Bradford Hill criteria are encouraged.

Summary of Safety Concerns

Products with an EU Risk Management Plan (RMP): the safety concern summary from the RMP at the start of the reporting interval must be included as a minimum
Products without an EU RMP: justification for each included safety concern is required
The PSUR is not a tool for harmonising safety concerns across products with the same active substance

Risk Minimisation Effectiveness

As per Regulation (EU) 2025/1466 (amending Implementing Regulation (EU) No 520/2012), PSURs must now include updates on the implementation and effectiveness of risk minimisation measures. These results should be reported in the EU regional appendix (section VII.C.5.5) and summarised in PSUR subsection 16.5.

Benefit-Risk Analysis

At the start of each PSUR period, the benefit/risk balance is assumed positive based on prior assessments
New efficacy data that only confirms the established benefit does not require full re-evaluation
Lack of efficacy or challenges to established efficacy must be discussed in sections 7 or 13 per GVP Module VII
PSURs cannot conclude on evidence of efficacy in new indications — a separate regulatory application is required

Assessment, Outcome, and Quality Systems

Requests for supplementary information are generally made at Day 60 of the procedure, with a 30-day response window
Line listings and CIOMS narratives will only be requested when duly justified
MAHs must have appropriate quality systems in place to ensure PSUR compliance
Significant quality failures may trigger a pharmacovigilance inspection