Relating Interfacial Shear and Dilatational Stresses to Protein Aggregation in mAbs

Abstract

Monoclonal antibodies (mAbs) have demonstrated tremendous potential as therapeutic products for various target diseases ranging from oncology to neurodegenerative diseases. However, aggregation of monomeric mAbs into higher-order structures is an undesired consequence of bioprocessing, transportation, and storage of these proteins. Interfacial stresses that arise from agitation, storage, interactions with the solid container walls, as well as interactions with the silicone oil that is used to lubricate the plunger in prefilled syringes have all been shown to contribute to aggregation of mAbs, although the exact mechanism of aggregation remains under investigation. In this chapter, we present the various interfaces encountered by monoclonal antibodies and discuss recent research efforts and analytical techniques that focus on how dilatation and shear stresses at the air-water interface can be related to formation of protein particles in bulk solutions. Newer techniques such as interfacial viscosity and rheology will also be discussed. Finally, we will review research efforts that focus on understanding the role of solid-liquid and liquid-liquid interfaces in this aggregation process.