Enablers for QbD implementation: Mechanistic modeling for ion-exchange membrane chromatography

Monoclonal antibody (mAb) based therapeutic products presently dominate the pipelines of most biopharmaceutical companies. Due to the large manufacturing requirements for these products, higher productivity is desirable and membrane chromatography has emerged a possible solution. In this study, a mechanistic model has been proposed for membrane chromatography for predicting product breakthrough at different mAb concentrations. First, Linear, Freundlich, Langmuir, and Temkin isotherms have been evaluated for their suitability with respect to modeling of adsorption of a monoclonal antibody therapeutic on an ion- exchange membrane adsorber. Next, pseudo-first-order, pseudo-second-order, modified Langmuir and steric mass action (SMA) adsorption kinetic models have been evaluated and compared. The results indicate that a combination of Langmuir isotherm and modified Langmuir or the pseudo-first order kinetic model provides the best prediction of mAb adsorption on ion-exchange membrane adsorbers. The final model could be successfully used to understand the adsorption kinetics between complex protein and ligand within the membrane device. The proposed approach would be of significant value to the biotech industry in ensuring the better development of future membrane adsorber devices with optimal sizing. (C) 2015 Elsevier B.V. All rights reserved.