(612d) Effect of Membrane Module Geometry on the Critical Flux for IgG Precipitates

Recent increases in monoclonal antibody titer from Chinese Hamster Ovary cell culture has led to renewed interest in precipitation for the initial capture / purification of these high-value proteins. In addition, it is possible to implement precipitation (in a tubular flow reactor) with tangential flow filtration to develop a fully continuous low-cost capture step that could be directly integrated into a continuous biomanufacturing process. The membrane units used for dewatering and washing the precipitated protein must be able to operate for extended times without fouling. In this work, we examined the effect of the membrane module geometry on the critical flux and fouling mechanisms using human serum Immunoglobulin G (IgG) as a model protein. IgG was precipitated by addition of 10 mM zinc chloride and 7 wt % polyethylene glycol in a tubular precipitation reactor. The critical flux was then evaluated using flux stepping experiments with both flat sheet membranes in open channel cassettes and hollow fiber membrane modules with different inner diameter. The hollow fiber modules had relatively low critical flux due to clogging of the fibers at the module inlet, with this behavior confirmed using both SEM imaging and hydraulic permeability data for the fouled modules. In contrast, the open channel cassettes showed much less fouling, with no evidence of channel clogging. Instead, the fouling occurred on the membrane surface leading to a reduction in the hydraulic permeability. The open channel cassettes could be operated continuously for at least 24 hours by using a filtrate flux that was about 20% below the experimentally determined critical flux, without any evidence of significant fouling. These results provide important insights into the origin of the fouling behavior during tangential flow filtration of precipitated proteins and the appropriate design of membrane processes for continuous capture of monoclonal antibody products.