Bioprocess Challenges in Purification of Therapeutic Protein Charge Variants

Biopharmaceuticals are complex therapeutic protein molecules produced in living cells and have been a major driving force for drug development in the pharmaceutical sector in recent years. Monoclonal antibodies (mAbs) are biological macromolecules used for treating life-threatening and rare illnesses. mAbs with post-translation alterations can be observed during the assessment of charge variants. Controlling the charge variant profile of therapeutic protein is a regulatory requirement to confirm that the macromolecule complies with the quality parameters to ensure patient safety. Unfortunately, manufacturing these biopharmaceuticals is very expensive. However, the emergence of biosimilars has reduced developmental cost across the biopharmaceutical industry. The advent of biosimilars has constrained the development of more efficient downstream bioprocesses that are mainly considered the bottleneck of the manufacturing process. This review focuses on the existing methods for charge variants separation and process optimization and indicates new approaches for future developments. It also provides a comprehensive summary for the biological community about the impact of charge variants.