Chapter 7 - Recent advances in ultrafiltration and virus filtration for production of antibodies and related biotherapeutics

Abstract

Virus filtration and ultrafiltration are critical technologies that play unique roles in all antibody purification processes. The need to remove both retroviral as well as potential adventitious contaminants is a regulatory requirement. Virus filtration is one of the key unit operations used to assure the viral safety of biopharmaceutical processes, via a robust size-exclusion mechanism. Tangential-flow ultrafiltration and diafiltration is employed at the end of the downstream purification process just prior to bulk drug substance formulation. It provides an effective and efficient means to concentrate the protein to the final-fill target and exchange it into the formulation buffer appropriate for patient dosing. Recent industry trends such as high concentration formulations, intensified unit operations, connected and continuous processing, and implementation of single-use technology are changing the process conditions under which these filters need to operate successfully and increasing the performance expectations. In response, filter suppliers have developed products that are better suited to these new process demands, and both suppliers and end-users are redeveloping and reoptimizing how virus filtration and ultrafiltration are implemented into manufacturing processes. In addition, the evolving Regulatory landscape for addressing the industry trends, particularly with respect to virus filtration, has resulted in innovations in validation strategies.