Biosimilar therapeutics-what do we need to consider?

Abstract

Patents for the first generation of approved biopharmaceuticals have either expired or are about to expire. Thus the market is opening for generic versions, referred to as 'biosimilars' (European Union) or 'follow-on protein products' (United States). Healthcare professionals need to understand the critical issues surrounding the use of biosimilars to make informed treatment decisions.The complex high-molecular-weight three-dimensional structures of biopharmaceuticals, their heterogeneity and dependence on production in living cells makes them different from classical chemical drugs. Current analytical methods cannot characterize these complex molecules sufficiently to confirm structural equivalence with reference molecules. Verification of the similarity of biosimilars to innovator biopharmaceuticals remains a key challenge. Furthermore, a critical safety issue, the immunogenicity of biopharmaceuticals, has been highlighted in recent years, confirming a need for comprehensive immunogenicity testing prior to approval and extended post-marketing surveillance.Biosimilars present a new set of challenges for regulatory authorities when compared with conventional generics. While the demonstration of a pharmacokinetic similarity is sufficient for conventional, small-molecule generic agents, a number of issues will make the approval of biosimilars more complicated. Documents recently published by the European Medicines Agency (EMEA) outlining requirements for the market approval of biosimilars provide much-needed guidance. The EMEA has approved a number of biosimilar products in a scientifically rigorous and balanced process. Outstanding issues include the interchangeability of biosimilars and innovator products, the possible need for unique naming to differentiate the various biopharmaceutical products, and more comprehensive labelling for biosimilars to include relevant clinical data.

Fig. 1

Physicochemical and biological characteristics of non-innovator epoetin products available outside of the United States and Europe. (A) Isoelectric focusing (i)/ western blot (ii) isoform distribution of 11 non-innovator epoetins compared to Eprex® (E). The table shows the location where each sample was obtained. (B) Bioactivity, determined by an in vivo bioassay in mice, was higher than specifications in four samples (137–226%) and below specifications in two samples (71–75%) [35].

Fig. 2

Antibody-mediated pure red cell aplasia (PCRA) cases, 1997–2002. Data from Schellekens [18], by permission of Oxford University Press.