Large-scale mammalian cell culture

Hu, Wei Shou; Auniņš, John G.

doi:10.1016/s0958-1669(97)80093-6

Cited by 115 publications

(79 citation statements)

References 49 publications

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“…On the other hand, dissolved oxygen concentration the use of aeration rate with 0.05 vvm in STR showed significant differences comparing to the other operation systems (p<0.05). Studies on animal cell damage due to mechanical agitation and sparging aeration have shown that mechanical damage of freely suspended animal cells is related, in many cases, with gas bubbles, especially the bursting bubbles at the air-medium interface [2,[24][25][26]. The maximum cell concentration decreased concurrently with increasing aeration rate ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Animal tissue and/or cell culture has important implications in biotechnology in the production of vaccines, pharmaceuticals and antibodies (used for diagnosis and treatment) [1][2][3]. Moreover the culture of some animal cells can produce a correctly processed protein that can be secreted into the culture medium, which greatly facilitates the purification process [4].…”

Section: Introductionmentioning

confidence: 99%

“…Highly valuable and small demanded products can be produced in small scales however; some "bulk" products for immunization and treatment may possibly require large-scale bioreactors for their costefficient manufacturing [2,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Cultivation and comparison of BHK-21 anchorage semi-dependent cell line in different production systems

Ayyildiz-Tamis¹,

Nalbantsoy²,

Elibol³

et al. 2012

Turk J Bioch

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Aim: The investigation of the different culture systems in order to get high yield of baby hamster kidney (BHK) cell line. Materials and Methods: Different cultivation systems, vibrofermentor and 5-L stirred tank bioreactors, have been used for the production of BHK cell line. The production systems were evaluated with respect to pH, temperature, viable cell number, aeration rate and stirring speed. Results: BHK cells were successfully cultivated in vibrofermentor and stirred tank bioreactor (STR) systems. In addition, higher cell concentration was obtained with low aeration rate (0.005 vvm) comparing to those of 0.02 and 0.05 vvm. The cultivation in STR can be operated with low aeration rate due to decrease the expenditure and improve the cell productivity. Conclusion: In order to improve the cell yield of the anchorage semi-dependent cell line in pilot scale, it should be preferred that the cells are firstly adapted to suspension culture by vibrational stirring and then be cultivated in stirred tank bioreactor which is operated at low aeration rate. These results showed consistency with the previous studies. Key Words: BHK-21, stirred tank bioreactor, vibrofermentor Conflict of Interest: Authors have no conflict of interests. ÖZETAmaç: Bebek hamster böbrek (BHK) hücre hattında, hücre veriminin arttırılması ve pilot ölçekte elde edilmesi için üretim sistemlerinin incelenmesi. Gereç ve Yöntem: Bu çalışmada, BHK hücre hattının üretimi vibrofermentör ve 5 L karıştırmalı tank biyoreaktör kültür sistemleri kullanılarak gerçekleştirildi. Üretim sistemlerinin, pH, sıcaklık, canlı hücre derişimi, havalandırma ve karıştırma hızı gibi parametreleri değerlendirildi. Bulgular: BHK hücrelerinin, hem vibrofermentörde hem de karıştırmalı tank biyoreaktörde başarılı bir şekilde üretilebildiği görüldü. Ayrıca, 0.02 ve 0.05 vvm havalandırma hızlarında elde edilenlere göre düşük havalandırma hızında (0.005 vvm) daha yüksek hücre konsantrasyonlarına ulaşıldı. Düşük havalandırma hızlarında çalışan karıştırmalı tank biyoreaktörün hem maliyet hem de hücre verimliliği açısından daha uygun olduğu belirlendi. Sonuçlar: Yarı-yüzey bağımlı BHK hücrelerinin pilot ölçekli üretiminde yüksek verim elde edebilmek için, öncelikle vibrasyon türü karıştırma ile hücrelerin süspansiyon kültüre adaptasyonu ve ardından düşük havalandırma hızlarında çalıştırılan karıştırmalı tank biyoreaktörlerin kullanılması tercih edilebilir. Elde edilen bu sonuçlar daha önceki çalışmalar ile paralellik göstermektedir. Anahtar Kelimeler: BHK-21, karıştırmalı tank biyoreaktör, vibrofermentör. Çıkar Çatışması: Yazarların çıkar çatışması bulunmamaktadır.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cultivation and comparison of BHK-21 anchorage semi-dependent cell line in different production systems

Ayyildiz-Tamis¹,

Nalbantsoy²,

Elibol³

et al. 2012

Turk J Bioch

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“…6,7 Three plates were located in the Autocell 200 Ò at these positions: slot 9/level 1 (S9L1), slot 5/level 11 (S5L11), and slot 1/level 21 (S1L21). One reference plate was cultured in a non-robotized water-jacketed C0 2 incubator (IGO150; Jouan SA).…”

Section: Assaysmentioning

confidence: 99%

Evaluation of an Automated Cell Culture Incubator: The Autocell 200

Triaud¹,

Darmon

Cariou³

et al. 2003

JALA: Journal of the Association for Laboratory Automation

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We evaluated the benefits of automation on the technical performance of a new automated cell culture incubator, the Autocell 200®, developed by Jouan SA. In addition, we assessed the potential interference of the embedded mechanical parts on cell culture growth. We measured a throughput of 150 plates loaded per hour, and 120 plates unloaded per hour, which is compatible with an external robotic handler. The mean time of robotic gate opening was 7 s. The gate pathway minimized climate disturbances inside the incubator. For CO2, we used a delay between opening events of 1 min. Biological assay results did not demonstrate a significant difference between the automated incubator and a traditional manual incubator, but we concluded that automation using the Autocell 200® could provide meaningful benefits for cell culture.

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“…Today, fed-batch and perfusion cultures are the two dominant modes of industrial operation for the mammalian cell culture processes that require large amount of proteins (Hu and Aunins 1997). Whatever the production technology of choice is, development efforts are continuously invested in order to obtain production processes that warrant: high volumetric productivity, batch-to-batch consistency, homogenous product quality at low costs.…”

Section: Introductionmentioning

confidence: 99%

Optimization of the medium perfusion rate in a packed-bed bioreactor charged with CHO cells

2004

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In the present study, the optimal medium perfusion rate to be used for the continuous culture of a recombinant CHO cell line in a packed-bed bioreactor made of Fibra-Cel Ò disk carriers was determined. A first-generation process had originally been designed with a high perfusion rate, in order to rapidly produce material for pre-clinical and early clinical trials. It was originally operated with a perfusion of 2.6 vvd during production phase in order to supply the high cell density ($2.5 · 10 7 cell ml À1 of packed-bed) with sufficient fresh medium. In order to improve the economics of this process, a reduction of the medium perfusion rate by À25% and À50% was investigated at small-scale. The best option was then implemented at pilot scale in order to further produce material for clinical trials with an improved second-generation process. With a À25% reduction of the perfusion rate, the volumetric productivity was maintained compared to the first-generation process, but a À30% loss of productivity was obtained when the medium perfusion rate was further reduced to À50% of its original level. The protein quality under reduced perfusion rate conditions was analyzed for purity, N-glycan sialylation level, abundance of dimers or aggregates, and showed that the quality of the final drug substance was comparable to that obtained in reference conditions. Finally, a reduction of À25% medium perfusion was implemented at pilot scale in the second-generation process, which enabled to maintain the same productivity and the same quality of the molecule, while reducing costs of media, material and manpower of the production process. For industrial applications, it is recommended to test whether and how far the perfusion rate can be decreased during the production phase -provided that the product is not sensitive to residence time -with the benefits of reduced cost of goods and to simplify manufacturing operations.

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Large-scale mammalian cell culture

Cited by 115 publications

References 49 publications

Cultivation and comparison of BHK-21 anchorage semi-dependent cell line in different production systems

Cultivation and comparison of BHK-21 anchorage semi-dependent cell line in different production systems

Evaluation of an Automated Cell Culture Incubator: The Autocell 200

Optimization of the medium perfusion rate in a packed-bed bioreactor charged with CHO cells

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