Chemical Engineering Thermodynamics and Protein Adsorption Chromatography

Abstract

The process of chromatographic separation and purification of recombinant products is of singular importance to the biopharmaceutical industries because it is the only separation process that can deliver high-purity products. A prerequisite for the application of process simulation in the development of chromatographic separations is the quality of the thermodynamic models of adsorption equilibria. The first part of the paper outlines the general thermodynamic principles of protein adsorption equilibria using well-established thermodynamic concepts, theories, and models. In the second part of the paper we present four examples. The first example shows how oligomer formation will modify a chromatographic run. In the second example we explore the separation potential of oligomer formation in the design of a chromatographic purification step. The third example demonstrates how synergies in the thermodynamic model development can be obtained by combining disparate experiments, here, chromatographic experiments with solubility data. In the last example we analyze the general features of the interplay between salt and cosolvent in hydrophobic interaction chromatography and reversed phase chromatography using a model developed by Kirkwood.