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Fluctuations in dissolved oxygen concentration during a CHO cell culture process affects monoclonal antibody productivity and the sulfhydryl‐drug conjugation process
Author(s) -
Hippach Michael B.,
Schwartz Ian,
Pei Jian,
Huynh Jimmy,
Kawai Yasuaki,
Zhu Marie M.
Publication year - 2018
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.2697
Subject(s) - setpoint , productivity , chemistry , monoclonal antibody , titer , oxygen , aeration , biophysics , chromatography , biochemistry , antibody , biology , computer science , organic chemistry , immunology , artificial intelligence , economics , macroeconomics
During a CHO cell culture production process, important parameters are generally well controlled by a feedback mechanism (PID loop) in order to ensure consistency in both productivity and product quality. These parameters typically include pH, dissolved oxygen (DO), and temperature. While most of these parameters are very well controlled within their specific deadband, stable DO control can be challenging. Oscillations in DO concentration are not uncommon and these fluctuations can be exacerbated with an efficient mass transfer aeration strategy. In this study, where an IgG 2 producing cell line was used, we observed increased lactate accumulation accompanied by decreased titer production in lots with fluctuations in DO concentration (DO F ) when compared with lots with stable DO control (DO S ). We demonstrate that DO F had a greater impact on performance with respect to titer production and lactate accumulation than DO setpoint. Furthermore, we report that estimated specific oxygen uptake rates (qOURs) were lower in DO F lots when compared with DO S lots. We also report that purified mAb sourced from DO F lots yielded lower drug‐to‐antibody ratio (DAR) after the sulfhydryl‐targeted maleimide conjugation process when equivalent reducing agent was used. All mAb lots were within the analytical specifications for release, though a slight increase in measureable trisulfides were observed in DO F mAb lots. DO control aimed to minimize fluctuations around DO setpoint was essential for us to produce consistent DAR without adjusting the conjugation process. © 2018 American Institute of Chemical Engineers Biotechnol. Prog ., 34:1427–1437, 2018