A protocol to transfer a fed-batch platform process into semi-perfusion mode: The benefit of automated small-scale bioreactors compared to shake flasks as scale-down model.
Biotechnol Prog
; 35(2): e2757, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30479066
ABSTRACT
Continuous processes such as perfusion processes can offer advantages compared to fed-batch or batch processes in bio-processing improved product quality (e.g. for labile products), increased product yield, and cost savings. In this work, a semi-perfusion process was established in shake flasks and transferred to an automated small-scale bioreactor by daily media exchange via centrifugation based on an existing fed-batch process platform. At first the development of a suitable medium and feed composition, the glucose concentration required by the cells and the cell-specific perfusion rate were investigated in shake flasks as the conventional scale-down system. This lead to an optimized process with a threefold higher titer of 10 g/L monoclonal antibody compared to the standard fed-batch. To proof the suitability and benefit as a small-scale model, the established semi-perfusion process was transferred to an automated small-scale bioreactor with improved pH and dissolved oxygen control. The average specific productivity improved from 24.16 pg/(c*d) in the fed-batch process and 36.04 pg/c*d in the semi-perfusion shake flask to 38.88 pg/(c*d) in the semi-perfusion process performed in the controlled small-scale bioreactor, thus illustrating the benefits resulting from the applied semi-perfusion approach, especially in combination with controlled DO and pH settings. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35 e2757, 2019.
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Base de dados:
MEDLINE
Assunto principal:
Perfusão
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Automação
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Reatores Biológicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article