Lessons learned from biosimilar epoetins and insulins

Abstract

Patients with diabetes and renal failure may already be receiving biosimilar epoetin and may receive biosimilar insulin in the near future. Because these biosimilar pharmaceuticals (or follow-on biologics) are complex protein molecules manufactured in lengthy and inherently variable processes involving living organisms, they have the potential to induce an immunogenic, rather than a therapeutic, response. This response is dependent as much on the method of manufacture and formulation, as on the protein itself. Apparently small and innocuous differences in manufacture and formulation can lead to unforeseen clinical consequences. This article discusses two case studies illustrating this principle, that of three insulin formulations which were physicochemically similar to comparator insulins, but with pharmacokinetic and pharmacodynamic profiles sufficiently different to have potentially serious clinical consequences and that of Eprex, for which an apparently minor change in one formulation caused an upsurge of cases of pure red cell aplasia which resulted in fatalities or complete transfusion dependence. Comprehensive and rigorous testing and long-term pharmacovigilance programmes are essential to detect and forestall such consequences.