Use of the steric mass action model in ion-exchange chromatographic process development

Despite the preponderance of models in the literature, chromatographic proc ess development in industrial protein purification has traditionally been b ased on heuristic knowledge and expertise. In this work, we explore the fea sibility of using a mathematical model to guide process development and opt imization. The development of an anion-exchange step to separate an antibod y from its dimer is used as a paradigm to test this approach to process dev elopment. In the approach involving models, we show that the work required may be reduced to the task of determining conditions for adequate selectivi ty. Once these conditions are obtained, the steric mass action formalism is used to predict the preparative experimental results. Our results indicate that this model is able to accurately predict experimental results under h igh loadings with minimal parameter estimation. Finally, we identify ways i n which such models can be used to increase productivity and process robust ness. (C) 1999 Elsevier Science BN. All rights reserved.