Relating Collective Diffusion, Protein-Protein Interactions, and Viscosity of Highly Concentrated Monoclonal Antibodies through Dynamic Light Scattering

To understand and predict the viscosities of highly concentrated monoclonal antibody (mAb) solutions, it is important to characterize the protein-protein interactions (PPI) and how they influence the possible formation of protein clusters. Herein, the collective diffusion is measured by dynamic light scattering (DLS) for solutions of three different mAbs, each with various cosolutes to tune the PPI. The results are combined with measurements of static structure factor, S(0), and self-diffusion coefficient, D-s, to understand the behavior of viscosity at high concentration. The small degree of variation in the hydrodynamic factor, H(0), and solvent protein friction, f(sp)c(s), among systems with a wide range of viscosities suggests solvent-protein interactions have a small influence on viscosity. Measurements of net PPI such as S(0) and the diffusion interaction parameter, k(D), are predictive of high concentration viscosity across cosolutes for a single mAb, but not for multiple mAbs. In contrast, properties that characterize the presence of clusters in solution, such as the polydispersity index from DLS, PDI, and the coefficient of protein-protein friction, f(pp)c(p), exhibit stronger correlations to viscosity.