(55c) A Membrane Chromatography Platform for the Purification of Biologics.

Downstream processes play a critical role in the production of biologics. There is a need for novel equipment and process alternatives that increase productivity, reduce buffer and energy use, and reduce process mass intensity. The focus for most of these efforts is on single-use devices that are scalable and flexible, so they can accommodate an extremely diverse portfolio of products. Our group has developed a new class of nonwoven membranes for flowthrough removal of impurities and bind-and-elute product capture chromatography. These membrnes are endowed with large pores that reduce the pressure drop at high flow rates, enabling short residence times and are able to adsorb large biologics including oligonucleotides, viral vectors and exosomes. Grafted hydrogel layers on the fiber surface increase the binding capacity at short residence times for small biologics such as proteins, significantly increasing productivity. This presentation will focus on results obtained using poly(butylene) terephthalate (PBT) nonwoven fabrics grafted with glycidyl methacrylate (GMA) layers functionalized with strong and weak ion exchange ligands, and salt tolerant multimode ligands. Case studies of the purification of mAbs and AAV2 with real process streams will be presented, indicating that this type of chromatography membranes may be used instead of resin column chromatography and affinity ligands, reducing costs, increasing process flexibility and productivity.