Continuous optical in-line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality

Weinheim : Wiley-VCH 2021

Great efforts are directed towards improving productivity, consistency and quality of biopharmaceutical processes and products. One particular area is the development of new sensors for continuous monitoring of critical bioprocess parameters by using online or in-line monitoring systems. Recently, we developed a glucose biosensor applicable in single-use, in-line and long-term glucose monitoring in mammalian cell bioreactors. Now, we integrated this sensor in an automated glucose monitoring and feeding system capable of maintaining stable glucose levels, even at very low concentrations. We compared this fed-batch feedback system at both low (< 1 mM) and high (40 mM) glucose levels with traditional batch culture methods, focusing on glycosylation and glycation of the recombinant protein darbepoetin alfa (DPO) produced by a CHO cell line. We evaluated cell growth, metabolite and product concentration under different glucose feeding strategies and show that continuous feeding, even at low glucose levels, has no harmful effects on DPO quantity and quality. We conclude that our system is capable of tight glucose level control throughout extended bioprocesses and has the potential to improve performance where constant maintenance of glucose levels is critical. © 2021 The Authors. Biotechnology Journal published by Wiley-VCH GmbH

bioprocess monitoring; biosensors; cell culture; CHO cells; recombinant proteins; Batch cell culture; Cell proliferation; Feeding; Glucose sensors; Glycosylation; Mammals; Metabolites; Online systems; Quality control; Recombinant proteins; Constant maintenance; Continuous feeding; Continuous monitoring; Glucose level controls; Improve performance; In-line monitoring; Low concentrations; Product concentration; Monitoring; recombinant erythropoietin; glucose; animal cell; bacterium culture; bioprocess; blood glucose monitoring; cell growth; CHO cell line; controlled study; feedback system; female; glucose intake; glycation; glycemic control; low temperature; nonhuman; optical sensor; product quality; protein glycosylation; sialylation; animal; batch cell culture; bioreactor; Cricetulus; glucose blood level; hamster; Animals; Batch Cell Culture Techniques; Bioreactors; Blood Glucose; Blood Glucose Self-Monitoring; CHO Cells; Cricetinae; Darbepoetin alfa; Article; Text

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DELUH oai:www.repo.uni-hannover.de:123456789/12492
Lederle, M.; Tric, M.; Roth, T.; Schütte, L.; Rattenholl, A. et al.: Continuous optical in-line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality. In: Biotechnology Journal 16 (2021), Nr. 8, 2100088. DOI: https://doi.org/10.1002/biot.202100088
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