Polyethylene glycol precipitation: fundamentals and recent advances.

Abstract

Downstream processing continues to face significant bottlenecks due to current purification technologies and improvements in upstream. Chromatography systems have been the primary method for purification due to their high yields and purities. However, the use of high-titer-producing strains has highlighted limitations in chromatographic steps, including mass transfer limitations, low capacity, and scalability issues. These challenges, combined with the growing interest in fully continuous manufacturing processes, have led to a widespread interest in alternative to affinity chromatography systems. Polyethylene glycol precipitation has been demonstrated to be a powerful, flexible, easily scalable, and titer-independent methodology for purifying therapeutic proteins such as monoclonal antibodies, achieving yields and purities comparable to chromatography systems. Furthermore, it also holds great potential for simplifying the current purification processes of new modalities and overcome current bottlenecks in downstream processing. Herein, we discuss the latest advances in polyethylene glycol precipitation as a purification technology and explore its future research directions and potential applications.