De-Bottlenecking The UF | DF Steps — Enhancing Recovery And Efficiency In Continuous Downstream Processing

By P. Joshi, M. Barros, S. Tindal, M. Leuthold

The concepts of intensified and continuous bioprocessing are central to current discussions in biomanufacturing, offering the potential for more efficient and cost-effective production across upstream and downstream processes. Continuous tangential flow filtration (TFF) and diafiltration are critical technologies for downstream processing. This study introduces an innovative flat sheet membrane device designed for TFF diafiltration. The device facilitates buffer exchange in feed streams in a single pass, which helps minimize shear stress on the product. Contaminants, such as salts, media components, or molecules smaller than the ultrafiltration membrane cut-off, are continuously removed while using a buffer volume comparable to that of traditional recirculating diafiltration processes. The flat sheet membrane device is similar to conventional TFF cassettes, making it easy to scale and operate. Further, it only requires one additional buffer inlet, enabling continuous diafiltration without added complexity. In this work, ultrafiltration (UF) and diafiltration (DF) data are presented utilizing a model protein and real antibodies, processed with an automated lab-scale system for reproducible results. Explore findings to learn how this new approach can support continuous biomanufacturing processes.