In this chapter, we compare the challenges and best practices identified in the country chapters so that the in-depth analysis of selected Member States is complemented with a broader overview . In doing so, we aim to provide a better understanding of the practical implementation of the new European Union (EU) pharmacovigilance legislation across Member States .The chapter is structured as follows . First, the national pharmacovigilance systems are compared regarding their structural factors as well as their institutional frameworks . The second section deals with the main finding of this study, namely the underreporting of adverse drug reactions (ADRs) in the Member States . This finding is substantiated by identifying problems in terms of batch numbers for biological medicinal products (biologicals), scientific evaluation, signal detection and information processing . Finally, we present a comparison of factors contributing to underreporting . The key factors in this respect are as follows:• Lack of awareness • Complexity of ADR reporting • Lack of cooperation • Interconnectivity problems Key factors and the underlying reasons have been discovered through repeated rounds of trial and error, relying on pharmacovigilance literature, reports on the effectiveness of pharmacovigilance systems and interview data gathered for the selected cases . By probing the empirical evidence with a variety of categorisations, we aimed to find the right balance in the accurate reporting of specific reasons while relying on key factors for meaningful comparative analysis and generalisation .