A general workflow for tangential flow filtration perfusion scale‐up

Tangential flow filtration (TFF) perfusion using hollow-fiber modules offers substantial advantages over other mammalian cell retention technologies. Recently, increased awareness of Starling flow has helped to enhance filtration performance to similar, or even higher levels compared to alternative technologies. Despite these improvements, scaling TFF perfusion remains challenging and often requires time-consuming trial-and-error efforts. This manuscript presents a systematic, data-driven four-step workflow for designing and scaling TFF perfusion systems, integrating hydraulic considerations, bubble removal studies, and pump characterizations. While filter selection in TFF perfusion often receives significant attention, the design of the cell retention loop is commonly overlooked. However, this element plays a crucial role in system performance and can cause suboptimal pump operation, residence time issues, and bubble accumulation. The developed data-driven workflow facilitates the optimization of designs for generic TFF perfusion systems utilizing hollow-fiber modules, effectively bridging the gap between small-scale and manufacturing-scale implementations.

Keywords

Subject (DDC)

660 - Technische Chemie

Project

Event

Exhibition start date

Exhibition end date

Conference start date

Conference end date

Date of the last check

ISBN

ISSN

0006-3592
1097-0290

Language

English

Created during FHNW affiliation

Yes

Strategic action fields FHNW

Publication status

Published

Review

peer-reviewed

Open access category

Hybrid

License

Citation

Romann, P., Lee, K., Natarajan, V., Ley, D., Nilsson, C. N., García-Münzer, D., Schieman, D., Hajighasemi, M., Zaytsev, A., Friedman, J., Chappuis, L., Habicher, T., Jaques, C., Cohen, A., Gagnon, M., Chan, E., Karst, D. J., Giller, P., Sibilia, A., et al. (2026). A general workflow for tangential flow filtration perfusion scale‐up. Biotechnology and Bioengineering. https://doi.org/10.1002/bit.70335

Full item page