Building A Fully Single-Use Process: High Productivity Protein A Membrane Devices That Complement Disposable Upstream Technology

By Shunsuke Shiina, Ph.D., Chase Snyder, Neha Saxena, Ph.D., and Rodrigo Gonzalez, Ph.D, AGC Biologics

Utilizing single-use technologies enhances the downstream processing of antibody-based therapeutics by streamlining labor-intensive cleaning procedures, decreasing product changeover times in multi-product facilities, reducing the risks of cross-contamination, and minimizing bioburden.

The objective of this study was to showcase the capability of an intensified, fully single-use downstream process for a fed-batch cell culture harvest producing a representative monoclonal antibody at an industrial scale. A primary focus was to demonstrate the integrated performance of parallel manifolded Gore 1 Liter Devices, resulting in a total bed volume of 2 liters. Specifically, the aim was to culture approximately 500 L of antibody harvest and effectively purify this harvest, thereby exhibiting the feasibility of a full 2000 L batch. A successful demonstration of the capture step involves matching or exceeding critical quality attributes (CQAs) established from a Protein A resin column control that purified the same cell culture harvest.

CQAs established with the existing resin purification method were met, and scaling up from lab-scale devices was demonstrated. The study results were integrated with previously published data to show the potential for high-productivity affinity capture sufficient to handle up to 10 g/L titers at the 2000 L scale.