BioChem - DOS

A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells

Applied microbiology and biotechnology

Zalai, Dé nes; Hevé r, Helga; Lová sz, Krisztina; Molná r, Dó ra; Wechselberger, Patrick; Hofer, Alexandra; Pá rta, Lá szló Putics, Á kos; Herwig, Christoph

<P>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.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00253-016-7380-4) contains supplementary material, which is available to authorized users.</P>

2016

Springer Berlin Heidelberg

cc-by

0175-7598

1432-0614

100

16

pp.7011-7024

10.1007/s00253-016-7380-4

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART76204019

https://link.springer.com/content/pdf/10.1007%2Fs00253-016-7380-4.pdf

Cell culture; CHO; Product quality attributes; Monoclonal antibody; Control of specific productivity; Glycosylation