Modeling Preparative Cation Exchange Chromatography of Monoclonal Antibodies

Recent advances in computational power, scientific understanding, and analytical capabilities are enabling more mechanistic modeling in biotechnology. This chapter describes the development and application of a mechanistic model for industrially relevant monoclonal antibody–cation exchange (CEX) chromatography processes. Typical monoclonal antibody purification processes utilize a protein-A chromatography capture step followed by two polishing chromatography steps. CEX chromatography is being used extensively in monoclonal antibody purification as one of the polishing steps and has been shown to be effective at removing high molecular weight species and providing some removal of host cell proteins (HCPs) and DNAs. The CEX chromatography process is operated in bind and elute mode with the following process steps: equilibrate column with solution at low salt concentration, load column to a target product concentration, wash with equilibration solution, and elute product with a linearly increasing salt gradient. Truly leveraging a mechanistic modeling approach requires changing the way process development is performed.