Process Development for the Large Scale Production of Clinical Grade Human Monoclonal Antibody Using a Cytopilot Fluidized Bed Reactor

Klima, Gert; Kreismayr, G.; Müller, Dethardt; Schmatz, C.; Wiederkum, Susanne; Steinfellner, W.; Assadian, A.; Lhota, Gabriele; Blüml, G.; Doblhoff-Dier, O.; Katinger, Hermann

doi:10.1007/978-94-011-5404-8_71

Cited by 7 publications

(5 citation statements)

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“…In addition it should be mentioned here that the conditions of the fluidized bed culture were not optimized, whereas those of the CellCube were, indicating that cell growth and production rates can be much improved after some optimization studies. This, as well as the fact that the fluidized bed reactor was already scaled up to 120 L [92], indicates the great potential of this culture system for the large-scale production of retroviral vectors.…”

Section: Comparison Of Different Reactor Systems For the Production Omentioning

confidence: 92%

“…Further advantages are: good mass transfer and mixing characteristics, homogeneous cultivation system, very good potential for volumetric scale-up, sampling of the reactor content possible, no bed clogging by cell growth or gas bubble entrapment. Fluidized bed reactor systems have been evaluated for the production of monoclonal antibodies [93,[96][97][98], recombinant proteins [90,92,94,[98][99][100], and retroviral vectors [101,123].…”

Section: Fluidized Bed Reactormentioning

confidence: 99%

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State-of-the-art of the production of retroviral vectors

Merten

2004

J. Gene Med.

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Retroviral vectors are still the vectors that are used in the majority of gene therapy trials for treatment of acquired or inherited diseases. In this review, the present state-of-the-art of the production of retroviral vectors and the most important parameters, such as the choice of the producer cell line, stability issues, medium additives, serum, type of bioreactor, that influence production issues is presented and discussed in light of an optimal vector production. The available literature data clearly indicate that, on one hand, the choice of the producer cell line is of utmost importance for obtaining a high level producer cell line, and that, on the other hand, the optimization of the medium, e.g. the replacement of glucose by fructose, has a potential for improving vector production rates and titers. Finally, the use of high-density perfusion culture systems for adherent as well as for suspension cells presents the best choice for a production system, because high cell densities imply high reactor specific production rates, which must be associated with a rapid harvest of the produced vector, thus avoiding vector inactivation due to an extended residence time. The overall optimization of the cultivation and production parameters will have a significant impact on the use of retroviral vectors for gene therapy purposes.

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Section: Comparison Of Different Reactor Systems For the Production Omentioning

confidence: 92%

Section: Fluidized Bed Reactormentioning

confidence: 99%

State-of-the-art of the production of retroviral vectors

Merten

2004

J. Gene Med.

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“…Process development is concerned with establishing the optimal protocols and equipment that will provide good process economy and efficiency. Establishing the more critical parameters at the beginning of the process facilitates developing large-scale procedures (278,279…”

Section: Documentationmentioning

confidence: 99%

Cell growth on electrospun nanofiber mats from polyacrylonitrile (PAN) blends

Wehlage¹,

Blattner²,

Mamun³

et al. 2020

AIMS Bioengineering

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“…These include nutrient concentration, accumulation of by-products (Borys et al, 1994;Yang and Butler, 2000), pH (Borys et al, 1993(Borys et al, , 1994, and dissolved oxygen (Jan et al, 1997). Although several reports have shown the suitability of the Cytopilot¯uidized-bed bioreactor culture system for growing a variety of cell lines (Goldman et al, 1998;Klima et al, 1997;Kong et al, 1999;Muller et al, 1997;Reiter et al, 1991;Unerluggauer et al, 1992;Valle et al, 1998), few have studied cell metabolism and the quality of the resulting cell product. Several culture parameters could aect the metabolism of the cultured cells and hence the glycosylation of the secreted product.…”

Section: Introductionmentioning

confidence: 97%

Erythropoietin production from CHO cells grown by continuous culture in a fluidized‐bed bioreactor

Wang

Yang

Huzel

et al. 2001

Biotech & Bioengineering

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A Chinese hamster ovary (CHO) cell line that expresses human erythropoietin (huEPO) was in a 2-L Cytopilot fluidized-bed bioreactor with 400 mL macroporous Cytoline-1 microcarriers and a variable perfusion rate of serum-free and protein-free medium for 48 days. The cell density increased to a maximum of 23 x 10(6) cells/mL, beads on day 27. The EPO concentration increased to 600 U/mL during the early part of the culture period (on day 24) and increased further to 980 U/mL following the addition of a higher concentration of glucose and the addition of sodium butyrate. The EPO concentration was significantly higher (at least 2x than that in a controlled stirred-tank bioreactor, in a spinner flask, or in a stationary T-flask culture. The EPO accumulated to a total production of 28,000 kUnits over the whole culture period. The molecular characteristics of EPO with respect to size and pattern of glycosylation did not change with scale up. The pattern of utilization and production of 18 amino acids was similar in the Cytopilot culture to that in a stationary batch culture in a T-flask. The concentration of ammonia was maintained at a low level (< 2 mM) over the entire culture period. The specific rate of consumption of glucose, as well as the specific rates of production of lactate and ammonia, were constant throughout the culture period indicating a consistent metabolic behavior of the cells in the bioreactor. These results indicate the potential of the Cytopilot bioreactor culture system for the continuous production of a recombinant protein over several weeks.

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Process Development for the Large Scale Production of Clinical Grade Human Monoclonal Antibody Using a Cytopilot Fluidized Bed Reactor

Cited by 7 publications

References 0 publications

State-of-the-art of the production of retroviral vectors

State-of-the-art of the production of retroviral vectors

Cell growth on electrospun nanofiber mats from polyacrylonitrile (PAN) blends

Erythropoietin production from CHO cells grown by continuous culture in a fluidized‐bed bioreactor

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