(374b) Pilot-Scale Design of Downstream Processing for Viral Therapeutics Using Aqueous Two-Phase Systems

There is an increasing demand for new viral-based vaccines and therapies to treat and prevent infectious diseases. Due to the increasing need and limited yields with current downstream unit operations for viral therapeutic production, alternative and high throughput technology developments are necessary. Also, the focus on cost reduction while increasing throughput is driving the desire for continuous processing in end-to-end manufacturing. However, the complexity, fragility, and lack of complete characterization of virus surfaces are hindering the development of platform processes for downstream operations. To address the yield and throughput challenges, we have explored a non-conventional method, aqueous two-phase system (ATPS), to improve current unit operations. ATPS is formed by mixing two partially miscible solutions that provide inexpensive, mild, and environmentally-friendly advantages over conventional methods. In our previous work with a polyethylene glycol (PEG) and citrate system, we have determined the key influential driving forces necessary for optimization to achieve near-complete separation of viruses and contaminants within a compact experimental space. A better understanding of the partition mechanism has made this method viable which was a key factor in restraining industrial implementation of ATPS. In this study, we will address the engineering design considerations (e.g. mixing rates, settling rates, settler sizing) of ATPS to operate at a large scale and in continuous mode. This work will supplement the drive to use ATPS as a continuous unit operation at industrial scale to enhance the throughput of viral therapeutic products at reduced production costs.