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Modulation of transmembrane pressure in manufacturing scale tangential flow filtration N‐1 perfusion seed culture
Author(s) -
Karst Daniel J.,
Ramer Kevin,
Hughes Erik H.,
Jiang Canping,
Jacobs Pieter J.,
Mitchelson Fernie G.
Publication year - 2020
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.3040
Subject(s) - volumetric flow rate , filtration (mathematics) , bioreactor , concentration polarization , permeation , membrane , materials science , perfusion , biomanufacturing , fouling , chemistry , chromatography , biomedical engineering , analytical chemistry (journal) , mechanics , biology , microbiology and biotechnology , mathematics , biochemistry , medicine , statistics , physics , organic chemistry , cardiology
Mammalian cells were grown to high density in a 3,000 L culture using perfusion with hollow fibers operated in a tangential flow filtration mode. The high‐density culture was used to inoculate the production stage of a biomanufacturing process. At constant permeate flux operation, increased transmembrane pressures (TMPs) were observed on the final day of the manufacturing batches. Small scale studies suggested that the filters were not irreversibly fouled, but rather exposed to membrane concentration polarization that could be relieved by tangential sweeping of the hollow fibers. Studies were undertaken to analyze parameters that influence the hydrodynamic profile within hollow fibers; including filter area, cell density, recirculation flow rate, and permeate flow rate. Results indicated that permeate flow rate had the greatest influence on modulating TMP. Further evaluation showed a significant decrease in TMP when permeate flow was reduced, and this occurred without any negative effect on cell growth or viability. Hence, a 30% reduction of permeate flow rate was implemented at manufacturing scale. A stable operation was achieved as TMP was successfully reduced by 75% while preserving all critical factors for performance in the perfusion bioreactor.