An Empirical Quantitative Model Describing Simultaneously Temperature and Concentration Effects on Protein Solution Viscosity.

ABSTRACT

The viscosity of high-concentration protein solutions can lead to a range of challenges in drug product manufacturing and administration. Accurately modeling the viscosity of biologics solutions in response to changes in the formulation and surrounding environment is of significant interest and remains a challenge. Here, we show a practical method of modeling the viscosity of a therapeutic solution in response to changes in temperature and protein concentration. Our viscosity model consists of a Ross-Minton model of concentration dependence and a modified Arrhenius temperature dependence. We measured the viscosity as a function of concentration and temperature of 4 therapeutic antibodies in a range of potential clinical formulations. With these data, our model shows surprising generality, proving effective with different types of antibodies, formulations, and a range of more than 2 orders of magnitude in viscosity. Our approach is built on existing theory but provides a practical approach to modeling the viscosity of formulated drug product over the range of process-relevant concentrations and temperatures to better mitigate challenges in the drug manufacturing process.