A comprehensive approach for evaluating charge heterogeneity in biosimilars.

Charge heterogeneity is often evaluated during biosimilar development as it is a universal feature of monoclonal antibodies (mAbs). A common approach in the industry is to develop a biosimilar product with a similar overall charge profile as the reference product. However, uncertainty remains with this approach as the same charge profile in two different products may be caused by different mechanisms. In this work, we present a comprehensive investigation of the charge variants of a therapeutic monoclonal antibody and its biosimilar candidate. Not only did the candidate show a similar charge profile as the reference product, our studies revealed that the same factors contributed to the charge variants of the reference product and the biosimilar candidate. We believe our cause-based approach mitigates the risks associated with the profile-based method and is a rational approach for the charge evaluation of biosimilars.