Impact of hollow fiber length and inner diameter on critical flux and conversion during single-pass tangential flow filtration of precipitated IgG

Precipitation-based alternatives to Protein A chromatography have gained attention due to the increase in cell culture titers of monoclonal antibody (mAb) products. Single-pass tangential flow filtration (SPTFF) can be used to dewater and purify the precipitated mAb, but it can be challenging to achieve the high single-pass conversion needed for a cost-effective process. This work examines the effects of hollow fiber length and inner diameter (ID) on the critical flux and conversion during SPTFF of precipitated immunoglobulin G (IgG) as a model protein. The critical flux was evaluated using the flux-stepping method for hollow fibers with 0.5- and 1.0-mm ID and lengths of 20, 41.5, and 65 cm. The maximum conversion in the 0.5 mm ID fibers was greatest for the 41.5 cm length, with the conversion decreasing sharply for the 65 cm fiber due to clogging at the fiber inlet. This clogging could be largely eliminated by using 1.0 mm ID fibers, with conversions as high as 90 % achieved with the longest fibers. These findings highlight the significance of proper module design to achieve effective processing of precipitated proteins.