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Integration of Cell Culture with Continuous, On‐Line Sterile Downstream Processing
Author(s) -
GRANDICS P.,
SZATHMARY S.,
SZATHMARY Z.,
O'NEILL T.
Publication year - 1991
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1991.tb18595.x
Subject(s) - bioreactor , cell culture , downstream processing , continuous production , process (computing) , protein subunit , product (mathematics) , chemistry , microbiology and biotechnology , chromatography , process engineering , biochemistry , biology , computer science , engineering , chemical engineering , genetics , geometry , mathematics , organic chemistry , gene , operating system
The development of an integrated system for the continuous, automated production of pure cell culture derived proteins is discussed. The system comprises a cell culture subunit for the continuous culture of mammalian cells and a purification subunit linked on-line to the cell culture subunit. The cells are compartmentalized and continuously perfused with culture medium. The cell culture medium leaving the bioreactor is perfused through a sterile immunoaffinity column that instantaneously removes the product from the culture fluid. This results in improved product quality because the product is quickly removed from the cell culture, thus minimizing contact with degradative enzymes. The culture medium, stripped from the secreted product, is recirculated into the bioreactor. The system allows simple, automated, and economical production of purified proteins with higher quality than that possible with current production methods. The integration also allows on-line, real-time process monitoring, thus simplifying process development and allowing more consistent production of biologics.