Shear stress as a driver of degradation for protein-based therapeutics: More accomplice than culprit

Abstract

Protein degradation is a major concern for protein-based therapeutics. It may alter the biological activity of the product and raise the potential for undesirable effects on the patients. Among the numerous drivers of protein degradation, shear stress has been the focus around which much work has revolved since the 1970s. In the pharmaceutical realm, the product is often processed through several unit operations, which include mixing, pumping, filtration, filling, and atomization. Nonetheless, the drug might be exposed to significant shear stresses, which might cooperatively contribute to product degradation, together with interfacial stress. This review presents fundamentals of shear stress about protein structure, followed by an overview of the drivers of product degradation. The impact of shear stress on protein stability in different unit operations is then presented, and recommendations for limiting the adverse effects on the biopharmaceutical formulations are outlined. Finally, several devices used to explore the effects of shear stress are discussed.

Keywords: Aggregation; Biotherapeutics; Drug product; Shear stress; Unfolding.