Development of a scale-up strategy for Chinese hamster ovary cell culture processes using the kL a ratio as a direct indicator of gas stripping conditions.,Biotechnology Progress

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Development of a scale-up strategy for Chinese hamster ovary cell culture processes using the kL a ratio as a direct indicator of gas stripping conditions.
Biotechnology Progress ( IF 2.9 ) Pub Date : 2020-04-16 , DOI: 10.1002/btpr.3000
Tomohiro Doi ₁ , Hideyuki Kajihara ₁ , Yasuo Chuman ₁ , Shinobu Kuwae _{1,

2} , Takashi Kaminagayoshi ₁ , Takeshi Omasa _{3,

4}

Affiliation

Herein, we described a scale‐up strategy focused on the dissolved carbon dioxide concentration (dCO₂) during fed‐batch cultivation of Chinese hamster ovary cells. A fed‐batch culture process for a 2000‐L scale stainless steel (SS) bioreactor was scaled‐up from similarly shaped 200‐L scale bioreactors based on power input per unit volume (P/V). However, during the 2000‐L fed‐batch culture, the dCO₂ was higher compared with the 200‐L scale bioreactor. Therefore, we developed an alternative approach by evaluating the k_La values of O₂ (k_La[O₂]) and CO₂ [k_La(CO₂)] in the SS bioreactors as a scale‐up factor for dCO₂ reduction. The k_La ratios [k_La(CO₂)/k_La(O₂)] were different between the 200‐L and 2000‐L bioreactors under the same P/V condition. When the agitation conditions were changed, the k_La ratio of the 2000‐L scale bioreactor became similar and the P/V value become smaller compared with those of the 200‐L SS bioreactor. The dCO₂ trends in fed‐batch cultures performed in 2000‐L scale bioreactors under the modified agitation conditions were similar to the control. This k_La ratio method was used for process development in single‐use bioreactors (SUBs) with shapes different from those of the SS bioreactor. The k_La ratios for the SUBs were evaluated and conditions that provided k_La ratios similar to the 200‐L scale SS bioreactors were determined. The cell culture performance and product quality at the end of the cultivation process were comparable for all tested SUBs. Therefore, we concluded that the k_La ratio is a powerful scale‐up factor useful to control dCO₂ during fed‐batch cultures.

更新日期：2020-04-16

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