Mining manufacturing data for discovery of high productivity process characteristics

Charaniya, Salim; Lê, Hương Giang; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei Shou

doi:10.1016/j.jbiotec.2010.04.005

Cited by 74 publications

(57 citation statements)

References 23 publications

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“…The results here show that copper sulfate supplementation could reduce the sensitivity of cell metabolism to glucose level and improve process robustness. The performance difference between CFB-1 and CFB-2 is similar to what was observed in other fed-batch cultures, where divergence in lactate metabolism caused a significant difference in bioreactor titer [45].…”

Section: Optimized Concentrated Fed-batch Process (Cfb-2)supporting

confidence: 82%

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Hoshan

Chen

2016

Bioprocess Biosyst Eng

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In this study, we discussed the development and optimization of an intensified CHO culture process, highlighting medium and control strategies to improve lactate metabolism. A few strategies, including supplementing glucose with other sugars (fructose, maltose, and galactose), controlling glucose level at <0.2 mM, and supplementing medium with copper sulfate, were found to be effective in reducing lactate accumulation. Among them, copper sulfate supplementation was found to be critical for process optimization when glucose was in excess. When copper sulfate was supplemented in the new process, two-fold increase in cell density (66.5 ± 8.4 × 10(6) cells/mL) and titer (11.9 ± 0.6 g/L) was achieved. Productivity and product quality attributes differences between batch, fed-batch, and concentrated fed-batch cultures were discussed. The importance of process and cell metabolism understanding when adapting the existing process to a new operational mode was demonstrated in the study.

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Section: Optimized Concentrated Fed-batch Process (Cfb-2)supporting

confidence: 82%

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Hoshan

Chen

2016

Bioprocess Biosyst Eng

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“…However, this sometimes is a challenge in large-scale bioreactors since facility shutdown is often required for such activities. Minimum to no base addition is often viewed as an indicator for a good process, while a process that requires large amount of base addition could be problematic since base addition is typically related to high pCO 2 and/or high lactate accumulations (Charaniya et al, 2010;Nienow, 2006).…”

Section: Introductionmentioning

confidence: 99%

High-density mammalian cell cultures in stirred-tank bioreactor without external pH control

Chen

2016

Journal of Biotechnology

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“…The technique is not only of interest for the manufacturing step in industrial plants but also for the last two or three cultures performed during the cell expansion in the inoculum 'train' (Charaniya et al 2010). Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In order to guarantee consistent product formation on a high quality level, a highly precise production process must be constructed, which forms the product with a high batch-to-batch reproducibility. This is a key requirement in FDA's/EMA's PAT (FDA 2004) initiative, as currently the reproducibility obtained in production processes for recombinant proteins from animal cell cultures is not convincing (e.g., Charaniya et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

et al. 2010

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In order to guarantee the quality of recombinant therapeutic proteins produced in mammalian cell systems, the straightforward approach in industry is to run the processes as reproducible as possible. It is first shown that considerable distortions in the currently operated processes appear when the initial cell density deviates from its nominal value. Small deviations in the initial cell mass may lead to severe deviations from the desired biomass trajectory. Next, it is shown how to design a fed-batch production process in such a way that it is robust with respect to variations in the viable cell density. A simple open loop strategy is proposed for that purpose. Here we show for the first time at animal cell cultures (CHO cells) that by means of an appropriate glutamine feed rate profile F(t), which keeps the specific growth rate of the cells on a predefined value below its maximal value while maintaining the viabilities on a high level, the diverging viable cell count profiles change over into a robust converging set of profiles. The CHO cells used to validate the procedure could be focused to any specific growth rates below l max .

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Mining manufacturing data for discovery of high productivity process characteristics

Cited by 74 publications

References 23 publications

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

High-density mammalian cell cultures in stirred-tank bioreactor without external pH control

Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

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