Target Protein Production
Figure 5. Molecule titer 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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Concentration of the protein was measured by semi-automatic equipment with 10% of accuracy. Figure 5 shows protein concentration
(molecule titer), and Figure 6 shows protein concentration measured during runs but taking into account the accuracy of the
method.
Figure 6. Recombinant protein titer 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 with 10% accuracy of the quality control method.
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Despite different mixing technologies, lower IVC, and higher viability in orbital shaking bioreactor, all disposable bioreactors
demonstrated consistent protein concentration.
Their production performances seemed to be closer to process development bioreactors than production bioreactors.
When the accuracy of the quality control (QC) method was taken into account, protein concentration differences between bioreactors
were less obvious.
Process variability taking into account QC accuracy seemed to be higher in disposable bioreactors than traditional bioreactors.
This statement is not surprising as this process was better handled in traditional bioreactors than in new equipment.
Target Protein Quality Attributes
A recombinant protein was chosen for this project because its glycosylation pattern depended on cell culture conditions.
Figure 7. Recombinant protein quality for disposable bioreactors and 1250L MSB production bioreactor. HMW is for high molecular
weight molecule (aggregates). High molecular weight molecules could not be compared to 1250L production bioreactors due to
differences in sample treatment. Data are means from 2 bioreactors with errors bars representing minimum and maximum levels.
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Quality attributes (Figure 7) are critical for protein function, pharmacokinetics variables such as half-life and bioavailability,
immune response. They also may depend on the upstream part of the production process.
Figure 8. The pH measured after injecting sodium hydroxide in disposable bioreactors
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To generate a high quality molecule, a minimum specification for glycosylation was fixed (red line in Figure 7). All bioreactors
performed beyond this specification: disposable bioreactors, whatever mixing type, did not have a critical impact on this
quality attribute.
This observation also is valid for the aggregates; no major differences were observed between disposable bioreactors.
For that process, cell growth and viability profiles of disposable bioreactors were close to traditional bioreactors. The
productivity of disposable bioreactors was similar to MSB bioreactors. No impact of the mixing type was observed on molecule
quality attributes. The equipment can be used either as a seeding bioreactor or as a production bioreactor.
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