title: Model simulation and experimental verification of a cation-exchange IgG capture step in batch and continuous chromatography.
abstract: The cation-exchange capture step of a monoclonal antibody (mAb) purification process using single column batch and multicolumn continuous chromatography (MCSGP) was modeled with a lumped kinetic model. Model parameters were experimentally determined under analytical and preparative conditions: porosities, retention factors and mass transfer parameters of purified mAb were obtained through a systematic procedure based on retention time measurements. The saturation capacity was determined through peak fitting assuming a Langmuir-type adsorption isotherm. The model was validated using linear batch gradient elutions. In addition, the model was used to simulate the start-up, cyclic steady state and shut down behavior of the continuous capture process (MCSGP) and to predict performance parameters. The obtained results were validated by comparison with suitable experiments using an industrial cell culture supernatant. Although the model was not capable of delivering quantitative information of the product purity, it proved high accuracy in the prediction of product concentrations and yield with an error of less than 6%, making it a very useful tool in process development.
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Müller-Späth
authors.forename: G
authors.initials: G
authors.lastname: Ströhlein
authors.forename: L
authors.initials: L
authors.lastname: Aumann
authors.forename: H
authors.initials: H
authors.lastname: Kornmann
authors.forename: P
authors.initials: P
authors.lastname: Valax
authors.forename: L
authors.initials: L
authors.lastname: Delegrange
authors.forename: E
authors.initials: E
authors.lastname: Charbaut
authors.forename: G
authors.initials: G
authors.lastname: Baer
authors.forename: A
authors.initials: A
authors.lastname: Lamproye
authors.forename: M
authors.initials: M
authors.lastname: Jöhnck
authors.forename: M
authors.initials: M
authors.lastname: Schulte
authors.forename: M
authors.initials: M
authors.lastname: Morbidelli
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D002411:Cation Exchange Resins / Q000737:chemistry*; D002852:Chromatography, Ion Exchange / Q000295:instrumentation / Q000379:methods*; D007074:Immunoglobulin G / Q000737:chemistry / Q000302:isolation & purification*; D008956:Models, Chemical
chemical_list: D000911:Antibodies, Monoclonal; D002411:Cation Exchange Resins; D007074:Immunoglobulin G