(36a) New Modalities for Single-Pass Concentration and Purification of Biomolecules

Tangential Flow Filtration (“TFF”) has been the technology of choice for the concentration of biomolecules, for removing low molecular weight contaminants and buffer exchange since its invention in the 1970s.  While TFF is a very effective process for concentration and buffer exchange, it suffers from two inherent and undesirable characteristics:

1.    It requires a large recirculation of the retentate stream, which in turn requires large pumps and pipes, all of which generates large hold-up volumes and system complexity due to the all of the equipment required to deal with such a large recirculating stream (; a specialized tank; heat exchanger; valves; sensors; etc.).

2.   The process, as practiced in the bioprocessing industry, is inherently a batch process, exposing sensitive biomolecules to residence times of many hours.

 This paper will present the recently developed Single-pass TFF (“SP-TFF”) technology, commercialized by Pall Corporation in 2010 under the Cadence™ trade name.  In contrast to conventional TFF, SP-TFF eliminates the recirculation loop making it a continuous process with significant simplification of the processing system and reducing the residence time of the biomolecule from hours to 1 minute.  The continuous nature of SP-TFF has already found multiple applications in bioprocessing, particularly for the final concentration of mAbs and for inline volume reduction. New developments to improve the implementation of SP-TFF will also be presented. Finally, new concepts under development for concentration and purification of biomolecules will be presented.