(235h) Advective Flow Membrane Chromatography: Utilization of Flow-through Mode for Scalable, Single-Use Downstream mAb Processing

Membrane chromatography can be an effective downstream tool, overcoming many of the traditional problems associated with packed bed chromatography such as high pressure drops, low flow rates, dependence on intra-particle diffusion, and potential complications due to radial/axial dispersion limitations and other transport phenomenon. However, many membrane devices are limited by both dynamic binding capacity and resolution, thus limiting their effectiveness beyond pilot scales. This presentation demonstrates how these limitations are effectively overcome through the utilization of a train consisting of the Natrix HD-Q (quaternary amine) followed by the HD-Sb (sulfonic acid/t-butyl) single-use, advective flow membrane devices operated entirely in a flow through mode for mAb downstream polishing.

These devices allow effective removal of impurities such as host cell protein, DNA, and HMW species at high capacities (5 kg/L) while maintaining rapid flow rates (10 MV/min). Furthermore, both devices were optimized to run at the same pH and conductivity, eliminating the need for inter-step eluate adjustments. Together, the high capacities and flow rates, along with single-use functionality and the development of adjustment-free downstream processing, make these membranes a good option for large scale flexible and disposable downstream processing.