Continuous cell flocculation for recombinant antibody harvesting

Journal of Chemical Technology and Biotechnology
Daniel BurgstallerPeter Satzer

Abstract

Integrated continuous production technology is of great interest in biopharmaceutical industry. Efficient, flexible and cost effective methods for continuous cell removal have to be developed, before a fully continuous and integrated product train can be realized. The paper describes the development and testing of such an integrated continuous and disposable set-up for cell separation by flocculation combined with depth filtration. Screening of multiple flocculation agents, depth filters, and conditions demonstrated that the best performance was obtained with 0.0375% polydiallyldimethylammonium chloride (pDADMAC; a polycationic flocculation agent) in combination with Clarisolve® depth filters. Using this set-up, a 4-fold decrease of filtration area was achieved relative to standard filtration without flocculation, with yields of ≥97% and DNA depletion of up to 99%. Continuous operation was accomplished using a simple tubular reactor design with parallelization of the filtration. The reactor length was selected to allow a 13.2-min residence time, which was sufficient to complete flocculation in batch experiments. Continuous flocculation performance was monitored on-line using focused beam reflectance measurement. Filter switch c...Continue Reading

References

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Citations

Aug 7, 2018·Biotechnology and Bioengineering·Balaji SomasundaramLinda H L Lua
Apr 18, 2020·Biotechnology Journal·Jure SencarAlois Jungbauer
Jul 11, 2020·Engineering in Life Sciences·Gregory DutraPeter Satzer
Dec 12, 2019·Frontiers in Bioengineering and Biotechnology·Julian KoppChristoph Herwig
Dec 1, 2021·Critical Reviews in Biotechnology·Michael A MacDonaldTrent Munro

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Methods Mentioned

BETA
Protein A chromatography
size exclusion chromatography

Software Mentioned

Clarisolve
pDADMAC
[UNK]
Clarisolve®
iC FBRM

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