Epoetins: differences and their relevance to immunogenicity.

Recombinant human erythropoietin (epoetin) is a highly active molecule and as such is used at very low therapeutic concentrations that require stabilisation. Commercially available epoetins differ in the stabilisers used in their formulations, which result in variations between epoetin preparations in storage and handling requirements. The stability and solubility of the epoetins are also affected by differences in the carbohydrate moieties that exist between them. However, it is the difference in stabilising agents that is thought to be the major cause of the upsurge in pure red cell aplasia (PRCA) cases observed predominantly with one epoetin alfa formulation, Eprex (Johnson & Johnson). In 1998 the European formulation of Eprex was changed with the replacement of human serum albumin (HSA), by polysorbate 80 and glycine. This formulation change coincided with an increased incidence of PRCA. In contrast, the incidence of PRCA has remained low with other HSA-containing epoetin alfa products and with epoetin beta. Therefore, it appears that the change in Eprex formulation has resulted in reduced protein stability and increased immunogenicity.