A method for designing flow-through chromatography processes

Bio-Process Engineering Laboratory, Graduate School of Medicine, Yamaguchi University Biomedical Engineering Center (YUBEC), Yamaguchi University, Tokiwadai, Ube, 755-8611, Japan

Corresponding author: shuichi@yamaguchi-u.ac.jp

Abstract

Continuous manufacturing is expected to increase the productivity of the production of biologics such as protein drugs. However, it is not easy to build the continuous process especially for downstream processing as many unit operations (chromatography and membrane filtration) are involved. An operation method known as flow-through chromatography (FTC) is considered to be an efficient method for separating two components as the flow is continuous. In FTC, a target protein is eluted from the chromatography column without adsorption whereas contaminants are strongly bound. Since at least two different modes of chromatography are needed in order to remove contaminants, two FTC columns have to be connected in order to build the continuous process. This is not an easy task since the mobile phase properties (pH, salt, buffer ions) are different for the two columns. In this paper, we developed a method for designing FTC processes based on the mechanistic models that we have developed for linear gradient elution (LGE) of proteins. The distribution coefficient K as a function of salt concentration, I determined from LGE data were used for the simulation. It was found that the process is quite sensitive to a small change in I. This indicates that FTC processes are carefully monitored and controlled for the stable operation.