Zeitschrift für Molekulare Pharmazeutik und organische Prozessforschung

Abstrakt

The glycosimilarity subset of biosimilarity: the role of N-glycosylation in the regulatory approval of biosimilars

 Andras Guttman

N-glycosylation is one of the important post-translational modifications of therapeutic proteins, which may directly affect the safety and/or efficacy of both the innovator products and their biosimilars. In IgG1 type monoclonal antibody therapeutics, the conserved oligosaccharide moiety at Asn297 can determine major Fc related mechanisms of action including anti-inflammatory properties, antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and serum half-life. Batch-to-batch alterations in this particular glycosylation is a good indicator of the robustness of the manufacturing process. Therefore, N-glycosylation of monoclonal antibody therapeutics is among the important critical quality attributes, so the carbohydrate moieties of such biopharmaceuticals should be closely monitored during all stages of the development and manufacturing processes. Determination of the level of similarity between two N-glycosylation profiles (e.g., innovator and biosimilar), however, is still challenging due to the complexity of their glycoseparation profiles as well as the nature and potential effect of the different structures on safety and efficacy. Thus, assessing similarity at the N-glycosylation level is one of the most crucial part of analytical biosimilarity studies for glycosylated reference products. This presentation describes a glycoanalytical profile based similarity scoring approach (Glycosimilarity Index) that can be used to accurately calculate the level of similarity between the N-glycosylation profiles of any given reference and test items from manufacturing and regulatory point of views.