We evaluated Health Authority (HA) assess ment comments on Periodic Benefit-Risk Evaluation Reports (PBRERs) submitted to HAs worldwide across 4 years for six Marketing Authorisation Holders, identifying quality issues and recommending enhance ment measures. The analysis of 698 PBRER HA assessment reports (January 2021–December 2024) yielded 1635 individual comments categorised into five groups. Excluding non-quality-related observations, the most frequent category was safety assessment (41%), followed by missing/incomplete information (28%), data in consistencies/quality issues (23%), and structural/template non-compliance (8%). Recommendations were developed through pattern analysis of recurring issues and tailored to address specific deficiencies in each category, emphasising improved safety assessment methodologies and robust quality control processes. This comprehensive assessment highlights the importance of analysing HA comments to enhance PBRER quality. Implementing systematic data management and quality control minimises the risk of missing safety data and safeguards medicinal products’ benefit-risk profiles.