Application of mechanistic modelling in membrane and fiber chromatography for purification of biotherapeutics - A review

Mechanistic modelling is a simulation tool which has been effectively applied in downstream bioprocessing to model resin chromatography. Membrane and fiber chromatography are newer approaches that offer higher rates of mass transfer and consequently higher flow rates and reduced processing times. This review describes the key considerations in the development of mechanistic models for these unit operations. Mass transfer is less complex than in resin columns, but internal housing volumes can make modelling difficult, particularly for laboratory-scale devices. Flow paths are often non-linear and the dead volume is often a larger fraction of the overall volume, which may require more complex hydrodynamic models to capture residence time distributions accurately. In this respect, the combination of computational fluid dynamics with appropriate protein binding models is emerging as an ideal approach.