Size-based Degradation of Therapeutic Proteins - Mechanisms, Modelling and Control

Abstract Protein therapeutics are in great demand due to their effectiveness towards hard-to-treat diseases. Despite their high demand, these bio-therapeutics are very susceptible to degradation via aggregation, fragmentation, oxidation, and reduction, all of which are very likely to affect the quality and efficacy of the product. Mechanisms and modelling of these degradation (aggregation and fragmentation) pathways is critical for gaining a deeper understanding of stability of these products. This review aims to provide a summary of major developments that have occurred towards unravelling the mechanisms of size-based protein degradation (particularly aggregation and fragmentation), modelling of these size-based degradation pathways, and their control. Major caveats that remain in our understanding and control of size-based protein degradation have also been presented and discussed.