Characterization of Product Related Variants in Therapeutic Monoclonal Antibodies

Abstract

The characterization of product-related variants in monoclonal antibodies involves identifying and quantifying the size and charge of variants that can impact the activity, efficacy, and safety of the antibodies. These variants represent distinct molecular forms that may arise from processes such as fragmentation, dimerization, aggregation, or post-translational modifications. The characterization of variants typically involves isolating the relevant species using a semi-preparative scale HPLC and analyzing them using various analytical techniques and biological assays. The commonly used analytical techniques include size-exclusion and ion-exchange chromatography, light scattering, mass spectrometry, capillary isoelectric focusing, and capillary electrophoresis-sodium dodecyl sulfate with ultraviolet or laser-induced fluorescence detection, among others. Additionally, functional assessments are performed using cell-based assays and binding assays to assess the biological activities of the variants. Identifying product-related variants through characterization enables the recognition of impurities that compromise the quality and safety of the drug.