Accelerated method for designing flow-through chromatography of proteins

Abstract

Continuous manufacturing including process integration is considered to improve the process economy of protein drug production. An operation method known as flow-through chromatography (FTC) is expected to be an efficient method for separating a target protein as a pseudo continuous method. In FTC, a target protein is eluted from the chromatography column without adsorption whereas contaminants are strongly bound. In this paper, we developed a simple and fast method for determining the sample feed volume for FTC processes by ion-exchange chromatography. The method uses the distribution coefficient as a function of mobile phase salt concentration, which can be determined by linear gradient elution experiments. The proposed method was verified by a model separation system (removal of dimer from BSA monomer by anion exchange chromatography).