Comparing Fed-Batch Cell Culture Performances of Stainless Steel and Disposable Bioreactors - A case study to compare the performances of several types of mixing in disposable bags with stainless

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Comparing Fed-Batch Cell Culture Performances of Stainless Steel and Disposable Bioreactors
A case study to compare the performances of several types of mixing in disposable bags with stainless steel bioreactors.


BioPharm International


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.
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.
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.
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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