Scalability of the Mobius CellReady Single-use Bioreactor Systems - The author defines the process-design space and demonstrates scalability of a single-use, stirred-tank bioreactor. - BioPharm

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Scalability of the Mobius CellReady Single-use Bioreactor Systems
The author defines the process-design space and demonstrates scalability of a single-use, stirred-tank bioreactor.


BioPharm International Supplements
Volume 26, Issue 4, pp. s11-s17

CELL CULTURE


Figure 4A: Viable cell density and viability vs. culture time for a batch culture process at the 2-L, 50-L, and 200-L working volumes. Data were obtained daily from the Vi-Cell XR (Beckman Coulter).
Maintaining a homogenous environment within the bioreactor is the most crucial criterion for a successful cell culture process. While different agitation strategies may be used to scale up a biomanufacturing process, power-per-unit volume is the most often used scaling parameter (3, 4). The second most important criterion for a successful cell culture run is efficient delivery of oxygen to maintain cell growth and productivity. Using these two criteria, a CHO cell culture batch process was performed in the 3-L, 50-L, and 200-L bioreactor systems using power per unit volume as the primary scaling parameter to demonstrate cell-culture scalability across the Mobius family of bioreactor systems. Further, gas flow rates were chosen to achieve similar kLa values for each vessel. The process parameters for each scale are outlined in Table V.


Figure 4B: Glucose and lactate Concentrations vs. culture time for a batch culture process at the 2-L, 50-L, and 200-L working volumes. Data were obtained daily from the BIOPROFILE FLEX system (NOVA Biomedical).
To demonstrate scalable cell culture performance, parameters including cell growth, viability and metabolism were compared For this study, samples were analyzed daily on a Vi-Cell XR (Beckman Coulter), a BIOPROFILE FLEX system (NOVA Biomedical) and a Blood Gas Analyzer (Siemens Rapidlab 248). As shown in Figure 4A, the viable cell densities and viabilities were comparable between all three scales. As shown in Figure 4B and 4C, the nutrient profiles and metabolic rates between all three scales were also comparable. The comparable cell growth, viabilities and metabolic profiles demonstrate that the cell culture performance in all three Mobius CellReady bioreactor systems is scalable.

CONCLUSIONS


Figure 4C: Metabolic rates for culture days 1–5 for a batch culture process at the 2-L, 50-L, and 200-L working volumes. Data were obtained daily from the BIOPROFILE FLEX system (NOVA Biomedical).
Successful scale-up of a biomanufacturing process is dependent on several factors including gas mass transfer, mixing efficiency and shear effects. An in-depth understanding of the process design space of the three Mobius CellReady bioreactor systems has beed developed through a series of experiments aimed at characterizing several key engineering parameters of the bioreactors. The three bioreactor systems, despite design and volume differences, are capable of achieving equivalent kLa values by adjusting the air flow rates at equivalent power-per-unit volume set points. In addition, similar system average mixing times can be achieved for the 50-L and 200-L systems within their power per unit volume operating range.

Based on an understanding of the design space of each of the bioreactor systems, process set points were chosen for CHO cell cultivation in each of these. Maintaining equivalent power per unit volume was chosen as the primary scaling parameter and gas flow rates were chosen based on achieving similar kLa values at each scale. During a 10-day batch culture, comparable cell growth, viability, and nutrient metabolism were achieved in each bioreactor system.

The comparable cell culture performance results with all three bioreactor systems demonstrate the scalability of the family of Mobius CellReady bioreactor systems. The comprehensive characterization of several key engineering parameters resulted in a detailed understanding of the design space of each bioreactor. This understanding allows users to choose process set points that enable successful scale-up of biomanufacturing process across the Mobius CellReady family from the 3-L to 200-L scale.

JENNIFER DEKARSKI is global product manager for single-use bioreactors at EMD Millipore, Bedford, MA.

REFERENCES

1. M. Shuler and F. Kargi, F. Bioprocess Engineering Basic Concepts, 2nd ed., (Prentice Hall, 2002).

2. D. M. Marks, Cytotechnology 42, 21-33 (2003).

3. Z. Xing. et al., Biotechnol. and Bioeng. 103, 733-746 (2009).

4. S.D. Kaiser et al., CFD for Characterizing Standard and Single-use Stirred Cell Culture Bioreactors. In Computational Fluid Dynamics Technologies and Applications (InTech, 2011).

5. Dalian University of Technology. Mixing, Chapter 6. http://ceb.dlut.edu.cn/uploads/soft/110415/7-110415154330.pdf.

6. A. W. Nienow, Cytotechnology 50, 9-33 (2006).


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