Insights

The European Medicines Agency has issued an Explanatory Note to Good Pharmacovigilance Practices (GVP) Module VII and a Questions & Answers guidance document for assessors on Periodic Safety Update Report Single Assessment (PSUSA). These documents have been developed to clarify specific aspects of the PSUSA procedure, particularly for nationally authorised medicinal products, and should be considered as interim guidance until GVP Module VII is formally revised.

This update provides clearer expectations on the level and quality of information to be included in PSURs, the presentation of signal evaluations, the assessment of risk minimisation measures, the use of EudraVigilance data, and the link between PSUR conclusions, Product Information updates and Risk Management Plan (RMP) implications.

Key points at a glance:

• Benefit-risk evaluation. The purpose of a PSUR and of the PSUSA procedure is to determine whether there are new risks, whether known risks have changed, or whether there are changes to the benefit-risk balance of the medicinal product.
• Urgent safety issues. PSURs are not intended as the first route for notifying urgent safety information with potential public health impact. These issues should be escalated and managed outside the PSUR through the appropriate regulatory pathway.
• Safety actions taken. Where significant actions have been taken for safety reasons, the MAH should provide sufficient detail on the rationale and potential impact on the benefit-risk profile.
• Patient exposure data. The number of patients exposed should preferably be provided together with exposure length, the methodology should be explained, and relevant discrepancies versus previous PSURs should be justified.
• Discrepancies between PSUR text and summary tabulations. Minor differences may occur because of different data lock points or dynamic safety databases, but substantial discrepancies that could affect the conclusions should be explained.
• Clear identification of new, ongoing and closed signals. The PSUR should include validated signals for which evaluation was completed or ongoing at the data lock point, regardless of the source of the signal or the actions taken.
• Cumulative signal evaluations. The MAH should describe the signal, its source or trigger, the evaluation methods, data sources, search criteria, key results and the rationale for refuting the signal or classifying it as an identified or potential risk.
• List of safety concerns. The guidance clarifies that the previous expectation that the PSUR list of safety concerns and the RMP safety specification should be identical is no longer a requirement, and this will be further clarified in the upcoming revision of GVP Module VII. The PSUR may justify changes to the list of safety concerns even where the RMP position differs, for example where a risk is sufficiently characterized and managed in the RMP but still remains relevant for PSUR follow-up.
• Known safety concerns. New information relevant to known safety concerns should be critically assessed, while data that merely confirm the established safety profile do not require extensive discussion.
• Product Information. PSUSA should not be used as a general harmonization tool for Product Information. However, where the assessment identifies sufficient evidence for a safety update, common wording may be recommended for the products covered by the procedure, where appropriate.
• Effectiveness of risk minimisation measures. Following the amendment of Implementing Regulation (EU) No 520/2012 by Regulation (EU) 2025/1466, PSURs are expected to include updates on the implementation and effectiveness of risk minimisation measures relevant to the benefit-risk assessment. MAHs should consider whether additional RMMs should be maintained, amended, partially discontinued or fully discontinued.
• EudraVigilance data. MAHs are expected to monitor data available in EudraVigilance and use them together with other available sources, where relevant.
• Issues not finalized within the PSUSA. The usual approach is to request follow-up in the next PSUR, while other regulatory routes may be considered where justified by the nature or urgency of the issue.
• EURD list entries for the same active substance. Splitting entries by indication or route of administration should only be considered where significantly different safety profiles are expected.

This guidance represents an important step toward improving the consistency, quality and regulatory usefulness of PSURs submitted under the PSUSA procedure. For MAHs, it is also a reminder to review internal PSUR processes, templates, quality control steps and cross-functional input from pharmacovigilance, regulatory affairs, medical and quality teams.

RPN remains available to support companies in the preparation, review and quality control of PSURs, the management of Product Information and RMP implications, and the alignment of pharmacovigilance procedures with the evolving GVP Module VII expectations.