Abstract:
:Detailed knowledge of mammalian cell culture proliferation kinetics is important to determine fed-batch strategies for industrial bioreactor operations. In particular, predicting the end of exponential proliferation in batch culture is a critical process parameter during culture scale-up. Using automated flow cytometry we show that an increase in the non-viable sub-population in CHO cell culture can predict the onset of stationary phase by approximately 40 h. This enables a completely automated culture scale-up process as well as a reliable and reproducible control of fed-batch additions during culture expansion. It is shown that the automated scale-up results in a significantly higher total cell count in the reactor than manual scale up initiated in stationary growth phase. During individual, subsequent culture expansions, a significant variation in the proliferation rate was observed despite control of bulk culture parameters. Thus, automated flow cytometry is critical to uncovering useful process parameters that enable new control strategies. Such improved process supervision derived from knowledge-based data analysis is central to the FDA's Process Analytical Technology (PAT) initiative and is expected to result in better and higher quality products.
journal_name
J Biotechnoljournal_title
Journal of biotechnologyauthors
Sitton G,Srienc Fdoi
10.1016/j.jbiotec.2008.03.019subject
Has Abstractpub_date
2008-06-01 00:00:00pages
174-80issue
2eissn
0168-1656issn
1873-4863pii
S0168-1656(08)00110-7journal_volume
135pub_type
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