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A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells
AuthorZalai, Dénes ; Hevér, Helga ; Lovász, Krisztina ; Molnár, Dóra ; Wechselberger, Patrick ; Hofer, Alexandra ; Párta, László ; Putics, Ákos ; Herwig, Christoph In der Gemeinsamen Normdatei der DNB nachschlagen
Published in
Applied Microbiology and Biotechnology, Berlin; Heidelberg, 2016, Vol. 100, Issue 16, page 7011-7024
PublishedBerlin; Heidelberg : Springer, 2016
Published version
The final publication is available at Springer via https://doi.org/10.1007/s00253-016-7380-4.
Document typeJournal Article
Keywords (EN)Cell culture / CHO / Product quality attributes / Monoclonal antibody / Control of specific productivity / Glycosylation
URNurn:nbn:at:at-ubtuw:3-1559 Persistent Identifier (URN)
 The work is publicly available
A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells [1.89 mb]Supplementary Material [0.59 mb]
Abstract (English)

The integration of physiological knowledge into process control strategies is a cornerstone for the improvement of biopharmaceutical cell culture technologies. The present contribution investigates the applicability of specific productivity as a physiological control parameter in a cell culture process producing a monoclonal antibody (mAb) in CHO cells. In order to characterize cell physiology, the on-line oxygen uptake rate (OUR) was monitored and the time-resolved specific productivity was calculated as physiological parameters. This characterization enabled to identify the tight link between the deprivation of tyrosine and the decrease in cell respiration and in specific productivity. Subsequently, this link was used to control specific productivity by applying different feeding profiles. The maintenance of specific productivity at various levels enabled to identify a correlation between the rate of product formation and the relative abundance of high-mannose glycoforms. An increase in high mannose content was assumed to be the result of high specific productivity. Furthermore, the high mannose content as a function of cultivation pH and specific productivity was investigated in a design of experiment approach. This study demonstrated how physiological parameters could be used to understand interactions between process parameters, physiological parameters, and product quality attributes.

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