einstein (São Paulo). 19/Feb/2019;17(1):eED4836.
Why are biosimilars much more complex than generics?
The regulatory demands for registering a generic medicine are physical-chemical tests and one comparative oral bioavailability clinical trial (bioequivalence).() This takes about 2 years, costs between USD$1 million and 2 million and enables claims for all indications accepted for the original drug. Demands for a biosimilar include many expensive and time-consuming comparative tests, and efficacy clinical trials for each indication. This takes from 5 to 9 years and costs over USD$100 million.()
The concept of generic medicine was developed for oral drugs, and biologics are mostly injectable. Moreover, the reasons for this huge difference are molecular complexity and the manufacturing process. The active pharmaceutical ingredients (APIs) of generics are small molecules, with a molecular weight of approximately 500 Daltons. Generic API purity and identity are mostly evaluated by inexpensive chromatographic tests. A bioequivalence clinical trial assesses the pharmacokinetic impact of the formulation and manufacturing of the API.() Since the APIs are the same, have the same concentration and a comparable bioavailability, regulatory authorities assume that the clinical effects will be the same for all indications.[…]