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Optimized process operations reduce product retention and column clogging in ATF-based perfusion cell cultures
Yuning Su1, Zhaohui Wei1, Yana Miao1
1Process Development, WuXi Biologics, 108 Meiliang Road, Wuxi, 214092, China.
Applied Microbiology and Biotechnology
|November 23, 2021
Summary
Product retention in hollow-fiber systems can be reduced by matching hollow fiber pore size to culture particle size. Optimizing flow rates and material choice also minimizes product loss and clogging in perfusion cell cultures.
Area of Science:
- Biotechnology
- Bioprocessing
- Cell Culture Technology
Background:
- Product retention in hollow-fiber membranes is a significant challenge in continuous cell culture systems.
- This phenomenon impacts the efficiency and yield of therapeutic antibody and recombinant protein production.
- Understanding the factors influencing product retention is crucial for process optimization.
Purpose of the Study:
- To investigate the impact of four key process parameters on product retention in hollow-fiber systems.
- To determine the relationship between hollow-fiber pore size and cell culture particle size distribution.
- To identify strategies for reducing product retention and preventing hollow-fiber clogging.
Main Methods:
- Utilized Chinese hamster ovary cells in an alternating tangential flow (ATF) system.
- Evaluated hollow fibers made of polysulfone and polyethersulfone with varying pore sizes (0.2 μm and 0.65 μm).
- Assessed the effects of harvest flow rate, ATF exchange rate, hollow fiber material, and pore size on product retention.
Main Results:
- Hollow fiber material significantly affected product retention, with polysulfone showing higher rates than polyethersulfone.
- Increased harvest flow rate and ATF exchange rate led to higher product retention.
- Hollow fibers with larger pore sizes (0.65 μm) showed increased retention, but this was dependent on the cell culture broth's particle size distribution.
- A correlation was found between hollow fiber pore size, culture particle size, and product retention, suggesting a need for matching.
Conclusions:
- The material of the ATF column and its pore size are critical factors influencing product retention.
- Optimizing harvest flow rate and ATF exchange rate can modulate product retention.
- Matching the hollow fiber pore size to the cell culture particle size distribution is essential for minimizing product retention and ATF column clogging in perfusion cultures.
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