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Open Access Research

Comparisons of optically monitored small-scale stirred tank vessels to optically controlled disposable bag bioreactors

Michael A Hanson123, Kurt A Brorson2, Antonio R Moreira1 and Govind Rao1*

Author Affiliations

1 Center for Advanced Sensor Technology, Chemical and Biochemical Engineering Department, University of Maryland Baltimore County, Baltimore, MD, 21250, USA

2 Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20903, USA

3 Wyeth Pharmaceuticals, Manufacturing Science and Technology, 401 N. Middletown Rd., Pearl River, NY 10965, USA

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Microbial Cell Factories 2009, 8:44  doi:10.1186/1475-2859-8-44

Published: 5 August 2009

Abstract

Background

Upstream bioprocesses are extremely complex since living organisms are used to generate active pharmaceutical ingredients (APIs). Cells in culture behave uniquely in response to their environment, thus culture conditions must be precisely defined and controlled in order for productivity and product quality to be reproducible. Thus, development culturing platforms are needed where many experiments can be carried out at once and pertinent scale-up information can be obtained.

Results

Here we have tested a High Throughput Bioreactor (HTBR) as a scale-down model for a lab-scale wave-type bioreactor (CultiBag). Mass transfer was characterized in both systems and scaling based on volumetric oxygen mass transfer coefficient (kLa) was sufficient to give similar DO trends. HTBR and CultiBag cell growth and mAb production were highly comparable in the first experiment where DO and pH were allowed to vary freely. In the second experiment, growth and mAb production rates were lower in the HTBR as compared to the CultiBag, where pH was controlled. The differences in magnitude were not considered significant for biological systems.

Conclusion

Similar oxygen delivery rates were achieved in both systems, leading to comparable culture performance (growth and mAb production) across scales and mode of mixing. HTBR model was most fitting when neither system was pH-controlled, providing an information-rich alternative to typically non-monitored mL-scale platforms.