Scale-up analysis for a CHO cell culture process in large-scale bioreactors

Biotechnology and Bioengineering

Volumn 103, Issue 4, 2009, Pages 733-746

  Xing, Zizhuo ^a   Kenty, Brian M ^a   Li, Zheng Jian ^a   Lee, Steven S ^a,b  

^a BRISTOL MYERS SQUIBB COMPANY   (United States)

^b Singapore Science Park II   (Singapore)

Author keywords

Dissolved carbon dioxide removal rate; Mathematical model; Mixing time; Oxygen transfer coefficient; Process scale up

Indexed keywords

AIR SPARGING RATES; BIOPROCESS; BIOTECHNOLOGY INDUSTRY; BULK MIXING; CARBON DIOXIDE REMOVAL; CELL-FREE; CHO CELL; CURRENT CONFIGURATION; DISSOLVED CARBON DIOXIDE REMOVAL RATE; EMPIRICAL EQUATIONS; ENGINEERING PARAMETERS; FED BATCHES; FUNDAMENTAL COMPONENT; LIQUID VOLUME; MAMMALIAN CELL CULTURE; MIXING TIME; OXYGEN TRANSFER; OXYGEN TRANSFER COEFFICIENT; POWER INPUT; PROBE TECHNIQUE; PROCESS DEVELOPMENT; PROCESS SCALE-UP; PRODUCTION SCALE; SCALE-5; SCALE-UP; SCALING-UP; THRESHOLD ANALYSIS; VIABLE CELLS;

ANIMAL CELL CULTURE; BIOCONVERSION; BIOREACTORS; CARBON DIOXIDE; CARBON DIOXIDE PROCESS; CELL CULTURE; CELL MEMBRANES; COMPUTER SIMULATION; DISSOLUTION; INDUSTRIAL CHEMICALS; MAMMALS; MATHEMATICAL MODELS; MIXING;

DISSOLVED OXYGEN;

CARBON DIOXIDE; OXYGEN;

ANIMAL CELL; ARTICLE; BIOREACTOR; CELL CULTURE; CELL DENSITY; CHEMICAL ENGINEERING; CHO CELL; CONTROLLED STUDY; CULTURE TECHNIQUE; NONHUMAN; PH MEASUREMENT; SCALE UP;

ANIMALS; BIOREACTORS; BIOTECHNOLOGY; CELL CULTURE TECHNIQUES; CHO CELLS; CRICETINAE; CRICETULUS; CULTURE MEDIA; HYDROGEN-ION CONCENTRATION; OXYGEN;

MAMMALIA;

EID: 67650188204     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.22287     Document Type: Article

References (55)

1. Atikinson A, Mavituna F. 1983. Biochemical Engineering and Biotechnology Handbook. New York: Nature Press, 1119 p.
2. Bonarius HPJ, de Gooijer CD, Tramper J, Schmid G. 1995. Determination of the respiration quotient in mammalian cell culture in bicarbonate buffered media. Biotechnol Bioeng 45:524-535.
3. Bylund F, Collet E, Enfors SO, Larsson G. 1998. Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases byproduct formation. Bioprocess Eng 18:171-180. (Pubitemid 28143904)
4. Chalmers JL. 1994. Cells and bubbles in sparged bioreactors. Cytotechnology 15:311-320.
5. Chisti Y. 1993. Animal cell culture in stirred bioreactors: Observations on scale-up. Process Biochem 28:511-517.
6. Cooke M, Middleton JC, Bush JR. 1988. Mixing and mass transfer in filamentous fermentations. In: Proceedings of the 2nd International Conference on Bioreactor Fluid Dynamics. Cranfield, UK: BHR Group, p. 37-64.
7. Croughan MS, Hamel J, Wang DIC. 1987. Hydrodynamic effects on animal cells grown in microcarrier cultures. Biotechnol Bioeng 29:130-141. (Pubitemid 17531771)
8. 2 and osmolality on hybridoma cells: Growth, metabolism and monoclonal antibody production. Cytotechnology 28:213-227.
9. deZengotita VM, Schmelzer AE, Miller WM. 2002. Characterization of hybridoma cell responses to elevated pCO2 and osmolality: Intracellular pH, cell size, apoptosis, and metabolism. Biotechnol Bioeng 77:369-380.
10. Ducommun P, Ruffieux P-A, Furter M-P, Marison I, von Stockar U. 2000. A new method for on-line measurement of the volumetric oxygen uptake rate in membrane aerated animal cell cultures. J Biotechnol 78:139-147. (Pubitemid 30139556)
11. Farid SS. 2007. Process economics of industrial monoclonal antibody manufacture. J Chromatogr B 848:8-18. (Pubitemid 46367764)
12. 2 production rate of mammalian cell suspension culture based on off-gas measurement. J Biotechnol 99:133-148.
13. 2 in largescale and high-density CHO cell perfusion culture. Cytotechnology 22:65-78.
14. Heath C, Kiss R. 2007. Cell culture process development: Advance in process engineering. Biotechnol Prog 23:46-51. (Pubitemid 46293485)
15. Heidemann R, Lutkemeyer D, Buntemeyer H, Lehmann J. 1998. Effects of dissolved oxygen levels and the role of extra- and intracellular amino acid concentrations upon the metabolism of mammalian cell lines during batch and continuous cultures. Cytotechnology 26:185-197. (Pubitemid 28222624)
16. Humphrey A. 1999. Shake flask to fermentor: What have we learned? Biotechnol Prog 14:3-7.
17. Jan DCH, Petch DA, Huzel N, Butler M. 1997. The effect of dissolved oxygen on the metabolic profile of a murine hybridoma grown in serum-free medium in continuous culture. Biotechnol Bioeng 54:153-164. (Pubitemid 27163486)
18. Jayapal KP, Wlaschin KF, Hu WS, Yap MGS. 2007. Recombinant protein therapeutics from CHO cells-20 years and counting. Chem Eng Prog 103:40-47.
19. Ju L-K, Chase GG. 1992. Improved scale-up strategies of bioreactors. Bioprocess Eng 8:49-53.
20. Junker BH. 2004. Scale-up methodologies for Escherichia coli and yeast fermentation processes. J Biosci Bioeng 97:347-364. (Pubitemid 38980915)
21. 2 and/or osmolality on the growth and recombinant tPA production of CHO cells. Biotechnol Bioeng 52:152-160.
22. Kirdar AO, Conner JS, Baclaski J, Rathore AS. 2007. Application of multi-variate analysis toward biotech processes: Case study of a cell-culture unit operation. Biotechnol Prog 23:61-67. (Pubitemid 46293488)
23. Langheinrich C, Nienow AW. 1999. Control of pH in large-scale, fed suspension animal cell bioreactors: Alkali addition and pH excursions. Biotechnol Bioeng 66:171-179. (Pubitemid 30010341)
24. Larsson G, Tornkvist M, Wernersson ES, Tragardh C, Noorman H, Enfors SO. 1996. Substrate gradients in bioreactors: Origin and consequences. Bioprocess Eng 14:281-289. (Pubitemid 26170344)
25. Lavery M, Nienow AW. 1987. Oxygen transfer in animal cell culture medium. Biotechnol Bioeng 30:368-373. (Pubitemid 17638764)
26. Lilly MD. 1983. Problems in process scale-up. In: Nisbet LJ, Winstanley DJ, editors. Bioactive microbial products. New York: Academic Press, p. 79-89.
27. Marks DM. 2003. Equipment design considerations for larger scale cell culture. Cytotechnology 42:21-33. (Pubitemid 37372943)
28. Marten MR. 1997. Rheology, mixing time, and regime analysis for a production-scale Aspergillus oryzae fermentation. In: 4th International Conference on Bioreactor & Bioprocess Fluid Dynamics. Bury St. Edmonds, UK: Mechanical Engineering Publication.
29. Marten MR, Wenger KS, Khan SA. 1997. Rheology, mixing time, and regime analysis for a production-scale Aspergillus oryzae fermentation. In: Nienow AW, editor. Bioreactor and bioprocess fluid dynamics. Cranfield, UK: BHR Group, p. 295-313.
30. Meier SJ, Hatton TA, Wang DIC. 1999. Cell death from bursting bubbles: Role of cell attachment to rising bubbles in sparged reactors. Biotechnol Bioeng 62:468-478. (Pubitemid 29052882)
31. Menisher T, Metghalchi M, Gutoff EB. 2000. Mixing studies in bioreactors. Bioprocess Eng 22:115-120.
32. Mitchell-Logean C, Murhammer DW. 1997. Bioreactor headspace purging reduces dissolved carbon dioxide accumulation in insect cell culture and enhances cell growth. Biotechnol Prog 13:875-877. (Pubitemid 28022040)
33. Mooyman JG. 1987. Sacling oxygen mass transfer in agitated fermentors. Biotechnol Bioeng 29:180-186. (Pubitemid 17059308)
34. Mostafa SS, Gu X. 2003. Strategies for improved dCO2 removal in largescale fed-batch cultures. Biotechnol Prog 19:45-51. (Pubitemid 36219302)
35. Nienow AW. 1997. On impeller circulation and mixing effectiveness in the turbulent flow regime. Chem Eng Sci 52:2557-2565. (Pubitemid 27347415)
36. Nienow AW. 1998. Hydrodynamics of stirred bioreactors. Appl Mech Rev 51:3-32.
37. Nienow AW. 2006. Reactor engineering in large scale animal cell culture. Cytotechnology 50:9-33. (Pubitemid 44243930)
38. Nienow AW, Langheinrich C, Stevenson NC, Emery AN, Clayton TM, Slater NKH. 1996. Homogenization and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production. Cytotechnology 22:87-94. (Pubitemid 27133776)
39. Osman JJ, Birch J, Varley J. 2001. The response of GS-NS0 myeloma cells to pH shift and pH perturbations. Biotechnol Bioeng 75: 63-73. (Pubitemid 32916700)
40. Osman JJ, Birch J, Varley J. 2002. The response of GS-NS0 myeloma cells to single and multiple pH perturbations. Biotechnol Bioeng 79:398-407. (Pubitemid 34847317)
41. Otomo N. 1996. A study of mixing with dual radial and dual axial flow impellers: Blending and power characteristics. UK: The University of Birmingham.
42. Pollard DJ, Kirschner TF, Hunt GR, Tong I-T, Stieber R, Salmon PM. 2007. Scale up of a viscous fungal fermentation: Application of scale-up criteria with regime analysis and operating boundary conditions. Biotechnol Bioeng 96:307-317. (Pubitemid 46232265)
43. Royce PNC, Thornhill NF. 1991. Estimation of dissolved carbon dioxide concentrations in aerobic fermentations. AIChE J 37:1680-1686.
44. Schmelzer AE, Miller WM. 2002. Hyperosmotic stress and elevated pCO2 alter monoclonal antibody charge distribution and monosaccharide content. Biotechnol Prog 18:346-353. (Pubitemid 34294247)
45. Schmidt FR. 2005. Optimization and scale up of industrial fermentation processes. Appl Microbiol Biotechnol 68:425-435. (Pubitemid 41549986)
46. Serrato JA, Palomares LA, Meneses-Acosta A, Ramirez OT. 2004. Heterogeneous conditions in dissolved oxygen affect N-glycosylation but not productivity of a monoclonal antibody in hybridoma cultures. Biotechnol Bioeng 88:176-188. (Pubitemid 39422989)
47. Spérandio M, Paul E. 1997. Determination of carbon dioxide evolution rate using on-line gas analysis during dynamic biodegradation experiments. Biotechnol Bioeng 53:243-252. (Pubitemid 27076417)
48. van't Riet K. 1979. Review of measuring methods and results in non-viscous gas-liquid mass transfer in stirred vessels. Ind Eng Chem Process Des Dev 18:357-364.
49. Varley J, Birch J. 1999. Reactor design for large scale suspension animal cell culture. Cytotechnology 29:177-205. (Pubitemid 29207781)
50. Vasconcelos JMT, Orvalho SCP, Rodrigues AMAF, Alves SS. 2000. Effect of blade shape on the performance of six-bladed disk turbine impellers. Ind Eng Chem Res 39:203-213. (Pubitemid 30048756)
51. Wayte J, Boraston R, Bland H, Varley J, Brown M. 1997. pH: Effects on growth and productivity of cell lines producing monoclonal antibodies: Control in large-scale fermenters. Genet Eng Biotechnol 17:125-132. (Pubitemid 27519162)
52. Xing Z, Li Z, Chow V, Lee SS. 2008. Identifying inhibitory threshold values of repressing metabolites in CHO cell culture using multivariate analysis methods. Biotechnol Prog 24:675-683. (Pubitemid 351832724)
53. Yang J-D, Lu C, Stasny B, Henley J, Guinto W, Gonzalez C, Gleason J, Fung M, Collopy B, Benjamino M, Gangi J, Hanson M, Ille E. 2007. Fed-batch bioreactor process scale-up from 3-L to 2,500-L scale for monoclonal antibody production from cell culture. Biotechnol Bioeng 98:141-154. (Pubitemid 47325831)
54. Yépez Silva-Santisteban BO, Maugeri Filho F. 2005. Agitation, aeration and shear stress as key factors in inulinase production by Kluyveromyces marxianus. Enz Microb Technol 36:717-724. (Pubitemid 40298892)
55. 2 and osmolality on growth of CHO cells and production of antibody-fusion protein B1: A case study. Biotechnol Prog 21:70-77.