Regulation in the Dynamic Environment of Complex Medicines

In this thesis, we evaluate the interface between parts of the regulatory system for medicine and real-world practice for embedding complex medicines. We conclude that regulation could benefit from better alignment with real-world practice, which is about finding the right balance between ‘over’ and ‘under’ regulation. The increasing complexity of current and future medicines poses major challenges to regulatory systems for safeguarding quality, safety and efficacy. In the past, medicines usually involved ‘small molecules’. Now see a shift towards increasingly complex molecular, biotechnological products whose production, control and use processes entail new scientific, clinical and regulatory challenges. Tailor-made precision treatments, decentralized production facilities and well-defined patient populations also require customized drug regulation. After all, increased complexity often goes hand in hand with a higher degree of risk and (remaining) uncertainty about quality, safety and efficacy. In the studies described in this thesis, we have approached this topic from the perspective of how to find an appropriate level of ‘regulatory density’. We also looked at aspects of so-called ‘post-approval learning’. Pharmacovigilance plays an important role in identifying possible new safety risks of approved medicines in order to control and reduce "residual uncertainty" step by step.