2022
DOI: 10.1002/elsc.202100161
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Scaling‐down biopharmaceutical production processes via a single multi‐compartment bioreactor (SMCB)

Abstract: Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale-down reactors. However, commonly applied multicompartment approaches comprising multiple reactors impose a bia… Show more

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Cited by 16 publications
(16 citation statements)
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References 29 publications
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“…In the SMCB, a compartment disc was installed inside the bioreactor below the second sampling port and above the second DO spot. The installation height of the disc was similar to the configuration in our previous characterization study (Gaugler et al, 2023) and created two similar‐sized compartments at the final working volume of 3.25 L. In the attempt to further approach the large‐scale environment in the SMCB, baffles were added to the reactor and optical sensor spots (PreSens) were used to monitor DO and pH. This way, nonscalable flow characteristics introduced by long probes were avoided and multiple measurement points for DO and pH could be realized.…”
Section: Methodssupporting
confidence: 73%
See 1 more Smart Citation
“…In the SMCB, a compartment disc was installed inside the bioreactor below the second sampling port and above the second DO spot. The installation height of the disc was similar to the configuration in our previous characterization study (Gaugler et al, 2023) and created two similar‐sized compartments at the final working volume of 3.25 L. In the attempt to further approach the large‐scale environment in the SMCB, baffles were added to the reactor and optical sensor spots (PreSens) were used to monitor DO and pH. This way, nonscalable flow characteristics introduced by long probes were avoided and multiple measurement points for DO and pH could be realized.…”
Section: Methodssupporting
confidence: 73%
“…Based on previous mixing time and power input determinations in the SMCB (Gaugler et al, 2023), fed‐batch cultivations were performed at three power inputs, simulating changing mixing times, and mass transfer across three hypothetical scales (Table 1). The mixing times represent macro mixing times and were evaluated via an optical pH‐dependent method at an acid‐to‐base ratio of 1:5 (Fitschen et al, 2021; Godleski & Smith, 1962).…”
Section: Methodsmentioning
confidence: 99%
“…In a well-mixed stirred-tank, there are little spatial variations in dissolved gas concentration (unlike plug-flow systems) so that the dissolved gas concentrations can be better controlled. Another potential scale-down system would be a two-stage STR, with a perforated plate separating two well-mixed zones [52]. In this way, the dynamic interchange between two concentrations could be reproduced, although the step transitions might be unrealistic for the observed large-scale behavior.…”
Section: Development Of Scale-down Simulatormentioning
confidence: 99%
“…biotechnological fermentation processes, with a radial impeller located near the gas inlet, for bubble dispersion, and an axial impeller for gas distribution across the volume 2–8;…”
Section: Introductionmentioning
confidence: 99%
“…Comprehensive investigations of these systems and their specific flow fields as well as design and construction recommendations are therefore still lacking. Potential applications of these combinations of different impeller types may include: -suspension processes, with an axial impeller near the reactor bottom, responsible for lifting up particles, and a radial impeller as the upper stage, for large-scale particle distribution [1]; -biotechnological fermentation processes, with a radial impeller located near the gas inlet, for bubble dispersion, and an axial impeller for gas distribution across the volume [2][3][4][5][6][7][8]; -processes involving internal heat exchangers; as shown by Ja ¨hrling and Schultz, single-stage impellers are rarely sufficient to ensure the required flow velocity and turbulence for adequate heat transport for multiple industrially used heat exchanger internal geometries [9]. Due to the mentioned lack of knowledge and design recommendations, assumptions how different impeller types can be combined reasonably have to be made.…”
Section: Introductionmentioning
confidence: 99%