Scientific Issues for Biogenerics/Biosimilars

Abstract

Recent changes in perspective at the US Food and Drug Administration and in the EU have clearly indicated a commitment to an abbreviated development and regulatory pathway for follow-on biological drugs (or biogenerics). This process has been discussed only in fairly abstract terms, however, and definitions and concrete requirements that could guide manufacturers of these products with regard to data requirements for an abbreviated submission are still needed. The aim of this paper is to summarise some of the critical scientific issues that will have an impact on the development of programmes for biogenerics. This paper discusses in some detail the likely necessity for developers of biogenerics to chemically and structurally characterise both their own follow-on product as well as the innovator's product in order to demonstrate a sufficient level of biosimilarity. Issues related to the characterisation of a biogeneric's biological activity are discussed, as are issues related to toxicity risks. It is the authors' belief that the term ‘biosimilar’, as opposed to the high level of required structural identity between a generic chemical drug and its innovative product, best describes the nature of follow-on biologics that would qualify for expedited development. Interpreting the clinical importance of demonstrated dissimilarities between innovator and biosimilar products is likely to be the greatest challenge for manufacturers of biogenerics, with requirements for human clinical testing being decided by regulatory agencies on a case by case basis.