EU Perspective on Biosimilars

Abstract

Biosimilars are regulated by the centralized marketing authorization procedure co-ordinated by the European Medicines Agency (EMA). Marketing authorization is granted by the Commission of the European Union (EU). Thus, each biosimilar has one regulatory assessment as well as the same product information and conditions of use in the EU. The current regulatory framework is a result of 20 years evolution of legislation and regulatory guidelines. The concept of biosimilarity is based on the long experience of comparability studies of individual biological products after manufacturing changes. Therefore, the development of a biosimilar is an extensive comparability exercise with head-to-head comparisons to its reference product that must have a full dossier of quality, safety and efficacy. For the sake of global development, the current guidance allows the use of a reference sourced from a non-EU country in certain non-clinical and clinical studies provided that it can be shown to be a relevant as a comparator. The high similarity of a biosimilar and its reference is demonstrated by physico-chemical and structural as well as in vitro functional comparability studies. Non-clinical in vivo studies are rarely needed. The extent of clinical studies depends on the possibilities to demonstrate high similarity by analytical tests. When the high analytical similarity has been established and the comparable pharmacokinetics and -dynamics, safety and efficacy have been demonstrated in one therapeutic indication, extrapolation safety and efficacy to other indications is expected. Several national regulatory agencies endorse physician-guided switches between biosimilars and reference products without additional clinical trials.