Chromatography has long been, and remains, the workhorse of downstream processing in the production of biopharmaceuticals. As bioprocessing has matured, there has been a growing trend toward seeking a detailed fundamental understanding of the relevant unit operations, which for some operations include the use of mechanistic modeling in a way similar to its use in the conventional chemical process industries. Mechanistic models of chromatography have been developed for almost a century, but although the essential features are generally understood, the specialization of such models to biopharmaceutical processing includes several areas that require further elucidation. This review outlines the overall approaches used in such modeling and emphasizes current needs, specifically in the context of typical uses of such models; these include selection and improvement of isotherm models and methods to estimate isotherm and transport parameters independently. Further insights are likely to be aided by molecular-level modeling, as well as by the copious amounts of empirical data available for existing processes.
Keywords: affinity chromatography; chromatography column simulation; general rate model; monoclonal antibodies; protein ion-exchange chromatography.