Modeling multicomponent adsorption of monoclonal antibody charge variants in cation exchange columns

Transport models are developed for the adsorption of monoclonal antibody charge variants in cation exchange columns for two different matrices: UNOsphere S, which has a macroporous architecture, and Capto S, which contains charged dextran polymers grafted to an agarose matrix. The UNOsphere S protein adsorption kinetics is described by a macropore diffusion model with effective pore diffusivity De = 8.3 × 10−8 cm2/s, which successfully predicts resolution of charge variants by frontal analysis at residence times, L/u, between 0.9 and 5.4 min. The Capto S adsorption kinetics is very fast for individual charge variants and for coadsorption of their mixtures, but is dramatically slower for sequential adsorption, when a more strongly bound variant displaces a more weakly bound one. A Maxwell‐Stefan model assuming single‐file diffusion predicts, in agreement with experiments, poor resolution of charge variants by frontal analysis even at long residence times as a result of highly hindered counterdiffusion.