Cell Growth During Production Phase
Figure 2. Integral of viable cells (IVC) in production phase at maximum working volume for disposable bioreactors, a 1,250
L MSB production bioreactor, and a 3.6 L process development bioreactor. Data are the means from two bioreactors, with errors
bars representing minimum and maximum levels.
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The production process includes a temperature switch to compare cell growth between bioreactors; therefore, an integral of
viable cells (IVC) was plotted instead of cell density (Figure 2).
Cell growth in disposable bioreactors using a paddle and stirred mixing system was similar to cell growth in traditional bioreactors;
however, cell growth in the orbital shaking bioreactor was lower.
The variability between runs was quite low, even when runs were carried out with different cell bank vials and cell amplifications.
Nevertheless, it is not relevant to conclude on robustness of disposable bioreactors as only two runs were performed.
Viability Profile During Production Phase
Figure 3. Viability in production phase at the maximum working volume for disposable bioreactors, a 1,250 MSB production
bioreactor, and a 3.6 L process development bioreactor. Data are the means from two bioreactors, with errors bars representing
minimum and maximum levels.
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Cell viability profile (Figure 3) could be linked to shear stress inside the bioreactor. This parameter could reflect the
impact of the mixing type.
Viability drop started at production day 6 for all bioreactors except the orbital shaking bioreactor. This particular bioreactor
has a completely different mixing profile compared with the others because nothing except the bag comes into contact with
cells. The agitation is external, while in other bioreactors mixing is generated by an internal element inside the bag. The
higher viability observed in orbital shaking could also be linked to the lower IVC presented in Figure 2.
In a same way as IVC, viability profiles with paddle and stirred mixing bioreactors were similar to traditional bioreactors.
Disposable bioreactors with internal agitation seemed to reproduce cell growth and viability profiles better than traditional
bioreactors.
Glucose Metabolism During Production Phase
Figure 4. Glucose concentration in production phase at the maximum working volume for disposable bioreactors, a 1,250 L MSB
production bioreactor, and a 3.6 L process development bioreactor. Data are the means from two bioreactors, with errors bars
representing minimum and maximum levels.
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Glucose is a key nutrient of cell metabolism and was followed (Figure 4) with a semi-automatic biochemistry analyzer.
Despite different cell densities especially in the orbital shaking bioreactor, glucose concentrations were similar between
all bioreactors throughout runs.
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