Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N -glycosylation of the innovator and a biosimilar version of etanercept

Borza, Beata and Szigeti, Marton and Szekrenyes, Akos and Hajba, Laszlo and Guttman, Andras (2018) Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N -glycosylation of the innovator and a biosimilar version of etanercept. Journal of Pharmaceutical and Biomedical Analysis, 153. pp. 182-185. ISSN 0731-7085

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Abstract

The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics andtheir biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serumclearance. In addition, alteration in glycosylation may influence the safety and efficacy of the product.Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoproteinbiotherapeutics, and consequently for their biosimilar counterparts. Thus, the carbohydrate moieties ofsuch biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during allstages of the manufacturing process. In this paper we introduce a rapid, capillary gel electrophoresis basedprocess to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity)between the innovator and a biosimilar version of etanercept (Enbrel®and Benepali®, respectively),based on their N-linked carbohydrate profiles. Differences in sialylated, core fucosylated, galactosylatedand high mannose glycans were all quantified. Since the mechanism of action of etanercept is TNF� bind-ing, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due toits influence on serum half-life.

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