A General Workflow for Tangential Flow Filtration Perfusion Scale-Up

Area of Science:

• Biotechnology
• Chemical Engineering
• Bioprocess Engineering

Background:

• Tangential flow filtration (TFF) perfusion with hollow-fiber modules is a key mammalian cell retention technology.
• Starling flow has improved TFF performance, but scaling remains difficult and iterative.
• Current TFF perfusion design often neglects the critical cell retention loop.

Purpose of the Study:

• To present a systematic, data-driven workflow for designing and scaling TFF perfusion systems.
• To integrate hydraulic, bubble removal, and pump characterization into the TFF design process.
• To optimize the cell retention loop design for improved TFF perfusion performance.

Main Methods:

• Developed a four-step data-driven workflow for TFF perfusion system design and scale-up.
• Integrated hydraulic considerations, bubble removal studies, and pump characterizations.
• Focused on optimizing the cell retention loop, often overlooked in TFF design.

Main Results:

• The workflow facilitates systematic design and scale-up of TFF perfusion systems.
• Optimized cell retention loop design addresses suboptimal pump operation and bubble accumulation.
• Successfully bridges the gap between small-scale and manufacturing-scale TFF perfusion.

Conclusions:

• A data-driven workflow enables efficient design and scale-up of TFF perfusion systems.
• Optimizing the cell retention loop is crucial for robust TFF perfusion performance.
• This systematic approach reduces trial-and-error in scaling TFF perfusion processes.