Optimized Purity And Recovery Of A Monoclonal Antibody Using Mixed-Mode Chromatography Media

Introduction

Monoclonal antibodies (mAbs) remain a predominant class of therapeutic protein products on the market because of their wide range of applications in disease treatment and diagnosis. Over the years, upstream technology advancements have helped improve the titer of target antibodies, from merely 1 g/L two decades ago to 10–13 g/L in fed-batch processes and up to 25 g/L in perfusion cultures today (Gronemeyer et al. 2014). However, these advancements have often adversely affected impurity composition and concentration upon harvest. This has had a significant impact on downstream processing. Elevated levels of antibody aggregates are often associated with the overproduction of mAbs due to the mispairing of disulfide bonds and the unfolding or denaturation of drug molecules at cell growth temperatures (25°C or above) (Rathore et al. 2013).