Predicting protein-protein interactions using the ePC-SAFT equation-of-state

Within the last decade, thermodynamic models have increasingly grown into the pharmaceutical industry, becoming an essential part in both, process development, as well as formulation development of small-molecule drugs. They are to an increasing degree accepted as a valuable building block to evaluate e.g. small-molecule formulation conditions. In contrast, modeling of highly complex (bio)-molecules (e.g. monoclonal antibodies) remains a challenging task and thermodynamic modeling is only rarely applied for e.g. protein formulations in the biopharmaceutical industry. Within this work, we developed a thermodynamic modeling approach to access protein-protein and proteinexcipient interactions (via second osmotic virial coefficients B-22 and cross viral coefficients B-23) for immunoglobulin G (IgG) and bovine serum albumin (BSA) in the presence of different excipients (NaCl, sucrose, L-histidine, L-arginine) at defined buffer conditions using the ePC-SAFT equation-of-state. The pure component parameters of IgG were determined based on the amino acid sequence and further fitted to experimentally determined static light scattering signals of IgG at buffer conditions. This approach allows to predict protein-protein and protein-excipient interactions of BSA and IgG in the presence of different excipient types and thus give access to protein phase behavior in these complex solutions. Applying this approach further allows to gain a mechanistic understanding on the complex interactions in solution that govern the phase behavior, and thus can aid an optimized formulation development. (C) 2019 Elsevier B.V. All rights reserved.