Disposable Systems as a Platform Technology for R&D and Clinical Supply - How a Big Pharma company tackled the move to disposable bioreactors. - BioPharm International

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Disposable Systems as a Platform Technology for R&D and Clinical Supply
How a Big Pharma company tackled the move to disposable bioreactors.


BioPharm International
Volume 23, Issue 8

SINGLE-USE BIOREACTOR EVALUATION AND COMPARATIVE RESULTS

Q: Is the engineering characterization to compare technical performance of SUBs with stainless steel bioreactors (SSBs) based on standard specifications for bioreactors?

The engineering characterization is based on performance specification for SSBs. All engineering numbers are available and these were the minimum numbers we wanted to achieve with disposable bioreactors.


Figure 1. Engineering characterization results of a comparison of stainless steel and single-use bioreactors (SUBs). Green shading indicates acceptable results. Yellow indicates acceptable with workaround/additional measures. Red indicates unacceptable.
Q: If we look at the engineering characterization results (Figure 1), it is clear that the performance of the SUBs in terms of power input is poor compared to SSBs, the best being 10% of the SSB. This results in poorer mixing times and mass transfer coefficients. Yet you have ranked the mixing times as acceptable. Why?

Although none of the bioreactors achieved an equivalent mixing time as the same size SSB, we used our knowledge of mixing times seen in the large-scale SSBs to define what was acceptable at this scale.

Q: The kLa also has a rating of acceptable with workaround/additional measures. Is this subsequently improved by sparging with O 2 ?

To achieve an acceptable O2 transfer rate, we have had to sparge the SUBs with O2. So we have had to install an O2 gas system for the SUBs.

PROCESS PERFORMANCE: PILOT-SCALE BIOREACTORS

Q: In your assessment, you found that rockers are suitable for the seed train. Is this because their performance is comparable to SSB and demands on the seed train are not significant?


Figure 2. Parallel fermentations in single-use bioreactor (SUB) rockers for seed production showed identical results for growth, productivity, cell size, distribution, apoptosis, and formation of byproducts. SSBs: stainless steel bioreactors
Rocker systems typically have a lower kLa which limits oxygen transfer and cell densities required, but for the seed train, the required cell density is much lower and achievable in a rocker system. We carried out 17 parallel fermentations in SUB rockers for seed production. These showed identical results for growth and productivity, cell size and distribution, apoptosis, and formation of byproducts (Figure 2). These SUB rocker systems with plug-and-play functionality now replace all our stainless steel seed bioreactors.

Q: What other factors are important for using rockers for the seed train?

Rockers are very beneficial for changeover. We run many more campaigns in rocker systems compared to a SSB. They are more flexible. You can change the inoculation date and then react very fast. We had rockers in place before the project started.


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