Biopharmaceutical Separations by Ultrafiltration

Department of Chemical Engineering, McMaster University, Hamilton, Ontario L8S 4L7, Canada 

Advanced Membrane Technology and Applications. Edited by Norman N. Li, Anthony G. Fane, W. S. Winston Ho, and T. Matsuura Copyright 2008 John Wiley Sons, Inc. 

This chapter will focus on the application of ultrafiltration in biopharmaceutical manufacturing. 

Ultrafiltration is a pressure-driven, permeability-based membrane separation technique, mainly used for processing macromolecules such as proteins, nucleic acids, and polysaccharides. Ultrafiltration membranes have pore size in the 1- to 100-nm range. The main separation mechanism is size-based sieving, but other factors such as electrostatic solute-membrane and solute-solute interactions can significantly affect separation (Saksena and Zydney, 1994 van Eijndhoven et al., 1995 van Reis et al., 1997 Nystrom et al., 1998 Ghosh and Cui, 1998). Hence, the still widely held view of ultrafiltration as a purely size exclusion process is incorrect. In order to use ultrafiltration as an efficient bioseparation technique, all factors influencing solute transmission through the membrane 

There are two main issues in an ultrafiltration process productivity and selectivity. Productivity is quantified in terms of the permeate flux, this being defined as the permeation rate per unit membrane surface area. Factors that affect permeate flux are solute type, solute concentration, membrane type, solution pH, solution ionic strength, apphed pressure (also called the transmembrane pressure), and the hydrodynamic conditions on the feed side. The volumetric permeate flux, which is the volume of permeate collected per unit time per unit membrane area is given by the following generalized equation, based on a resistance model  

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