Single-use, single-pass tangential flow filtration using low-cost hollow fiber modules

Increasing pressures on biomanufacturing costs have led to renewed interest in the development of single-use technologies that can be readily adapted to continuous processing. The objective of this study was to use commercially available hollow fiber membranes, originally designed for high-flux hemodialysis, for single pass tangential flow filtration with high conversions. Experiments were performed with solutions of Immunoglobulin G (IgG) using polysulfone hollow fiber membrane cartridges with a surface area of 1.9 m(2). The hollow fiber modules were able to provide more than 10-fold concentration of IgG in a single-pass with exit concentrations greater than 200 g/L. Stable operation was achieved during a continuous run for over a 120-h period with feed side pressure drops less than 1 kPa and transmembrane pressure drops less than 60 kPa. A single dialyzer was able to process 1.4 kg of IgG per day with a total cost of less than $0.004 per g of IgG. Flux-pressure profiles were in good qualitative agreement with a simple model accounting for concentration polarization effects and the variation of flux and pressure with axial position in the module. These results clearly demonstrate the potential of using these low-cost single-use hollow fiber modules for single-pass tangential flow filtration in continuous biomanufacturing.