Challenges and future perspectives of enhanced passive safety surveillance of influenza vaccines in Europe.

Postmarketing surveillance is critical for confirming the safety profile of vaccines following regulatory approval. This article contributes to the ongoing discussion on safety surveillance strategies for seasonal influenza vaccines in Europe. We examine the implementation of enhanced passive safety surveillance (EPSS) for seasonal influenza vaccines from season 2015/16 through season 2023/24, as conducted by a Marketing Authorization Holder in accordance with European Medicines Agency guidelines. We describe the evolution of data collection methods of EPSS studies conducted across nine seasons in Finland, United Kingdom, Republic of Ireland, Denmark, and Germany with different influenza vaccine formulations. Exposure data were prospectively collected in vaccination cards at the time of vaccination, while safety data collection evolved from telephone calls to electronic reporting systems. The use of an electronic system in recent seasons facilitated adverse drug reaction reporting by the vaccinees and improved real-time monitoring and accurate data collection. Operational challenges included country and site selection constraints and difficulty achieving target sample sizes and age group representation within short recruitment windows. Reporting rates varied across seasons, countries, and vaccine formulations, potentially influenced by factors such as vaccine reactogenicity, population demographics, and reporting behaviors. Future perspectives suggest the need for a unified Europe-wide safety surveillance system to enhance collaboration among regulatory bodies, public health agencies, and vaccine manufacturers, ultimately contributing to a more robust and reliable safety framework for influenza vaccines.