Development of biosimilars

Legislation allowing the approval of competitor versions of biopharmaceuticals, so-called biosimilars, has been in place in the European Union (EU) since 2004. For the marketing authorization of a biosimilar the European Medicine Agency (EMA) expects a full quality dossier and in addition, comparative analytical, pre-clinical and clinical studies demonstrating comparable quality, safety and efficacy to a product authorized in the EU. At present 13 biosimilar products have been authorized in the EU, epoetins, filgrastims and human growth hormones. These products are comparatively simple molecules, homologues of human proteins with a physiological function and are used clinically mainly as supportive or supplemental therapy. As the patents of some of the top selling and expensive monoclonal antibodies (MABs) used in cancer therapy are about to expire, there is a lot of interest in developing biosimilar versions of these products. Compared to currently approved biosimilars, MABs are much larger and complicated products. A European guideline for biosimilar MABs was relatively recently released. However, the development of biosimilar monoclonal antibodies will not be as simple as the first generation of biosimilars. Unlike the existing biosimilars, monoclonal antibodies have multiple biological functions, are used for functions that are normally not performed by antibodies and also are very specifically directed to intervene locally in the disease process that are complicated and not very well known. The concepts that have been used to show clinical similarity and extrapolation of indication will very difficult and even in many cases impossible to apply in the development of biosimilar monoclonal antibodies. The regulatory approach to this new class of biosimilars should be reconsidered, before affordable alternatives for the expensive anticancer monoclonal antibodies can be developed.