Viscosity Reduction and Stability Enhancement of Monoclonal Antibody Formulations Using Derivatives of Amino Acids

Abstract

Monoclonal antibodies are complex molecules that often require high concentration formulations to meet clinical requirement and bulk drug substance storage. Stability is a common concern in both high and low concentration formulations, however, high concentration formulations are further complicated by an increase in viscosity, leading to manufacturing and administration challenges. To manage stability and viscosity, drug developers typically use salt, amino acids, sugars, polyols, and surfactant. It is possible that excipients control some of the product quality attributes (CQAs), at the cost of several others. In this paper, we have evaluated several amino acid derivatives and identified bis acetyl lysine and propionyl serine to be efficient and superior to commonly used parenteral excipients for minimizing antibody solution viscosity, as well as mitigating physical and chemical degradation by controlling protein-protein interactions and deamidation.

Keywords: Deamidation; Formulation; High concentration; Monoclonal antibody; Protein-protein interactions; Stability; Viscosity.