Large-Scale Production of Monoclonal Antibodies

  • Cristina Glad
  • Inge Nilsson


The increased application of monoclonal antibodies in diagnostics and therapy has resulted in a demand for large quantities, grams to kilograms, to be produced. Traditionally, smaller quantities have been produced from hybridomas grown as ascites tumors in mice. However, this method is difficult to scale up and is not applicable to human hybridomas. The obvious alternative is in vitro cultures, which can be scaled up and made highly reproducible. Most culture systems have been originally designed for growth of microorganisms and do not always meet the specific demands of animal cells. Because these cells lack cell walls, they are very fragile and more sensitive to shearing forces than microorganisms. The airlift reactor is one example considered to have appropriate characteristics for shear-sensitive cells (Katinger, Scheirer, and Kromer, 1979) and has consequently been used for the production of monoclonal antibodies. Several developments have also been made to reduce the shearing forces in stirred-tank reactors while maintaining adequate oxygenation and mixing of the culture (Fazekas de St. Groth, 1983; Feder and Tolbert, 1983; Reuveny, Zheng, and Eppstein, 1986a).


Production Phase Oxygen Consumption Rate Good Manufacture Practice Animal Cell Culture Airlift Reactor 
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  1. Berg, G. J. (1985) Dev. Biol. Stand. 60, 297–303.PubMedGoogle Scholar
  2. Borrebaeck, C. A. K., and Ohlin, M. (personal communication).Google Scholar
  3. Carlsson, J., Nilsson, I. and Glad, C. (unpublished results).Google Scholar
  4. EC (1988) Guidelines on the Production and Quality Control of Monoclonal Antibodies of Murine Origin Intended for Use in Man Trends in Biotechnology, Vol. 6, G5–G8.Google Scholar
  5. Fazekas de St. Groth, S. (1983) J. Immunol. Methods 57, 121–136.CrossRefGoogle Scholar
  6. FDA (1987) Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use. Office of Biologics Research and Review, Center for Drugs and Biologics, FDA.Google Scholar
  7. Feder, J., and Tolbert, W. R. (1983) Sci. Am. 248, 24–31.CrossRefGoogle Scholar
  8. Griffiths, J. B. (1988) in Animal Cell Biotechnology, Vol. 3, (Spier, R. E. and Griffiths, J. B., eds.) pp. 179–220, Academic Press, London.Google Scholar
  9. Handa, A., Emery, A. N., and Spier, R. E. (1978) Dev. Biol. Stand. 66, 241–253.Google Scholar
  10. Himmelfarb, P., Thayer, P. S. and Martin, H. E. (1969) Science 164, 555–557.PubMedCrossRefGoogle Scholar
  11. Katinger, H. W. D., Scheirer, W., and Kromer, E. (1979) Ger. Chem. Eng., 31–38.Google Scholar
  12. Knazek, R. A., Gullino, P. M., Kohler, P. O., and Dedrick, R. L. (1972) Science 178, 65–66.PubMedCrossRefGoogle Scholar
  13. Lambert, K. J., Boraston, R., Thomson, P. W., and Birch, J. R. (1987) in Developments in Industrial Microbiology, Vol. 27, (Pierce, G., ed.) J. of Industrial Microbiology Suppl. No. 1; 1987, Society for Industrial Microbiology pp. 101–106.Google Scholar
  14. Lehman, J., Piehl, G. W., and Schulz, R. (1987) Dev. Biol. Stand. 66, 227–240.Google Scholar
  15. Lehman, J. (1988) Engineering Foundation Conference on Cell Culture Engineering, Abstracts, Palm Coast, FL.Google Scholar
  16. Reuveny, S., Zheng, Z.-B., and Eppstein, L. (1986a) Am. Biotechnol. Lab. Feb., 28–36.Google Scholar
  17. Reuveny, S., Velex, D., Miller, L., and MacMillan, J. D. (1986b) J. Immunol. Methods 86, 61–69.CrossRefGoogle Scholar
  18. Runstadler, P. W., Jr., and Cernek, S. R. (1988) in Animal Cell Biotechnology, Vol. 3, (Spier, R. E., and Griffiths, J. B., eds.) pp. 305–320, Academic Press, London.Google Scholar
  19. Scheirer, W. (1988) in Animal Cell Biotechnology, Vol. 3, (Spier, R. E. and Griffiths, J. B., eds.) pp. 236–281, Academic Press, London.Google Scholar
  20. Schonherr O. T., van Gelder, P. T. J. A. and van Hees, P. J., von Os, A. M. J. M., and Roelofs, H. W. M. (1987) Dev. Biol. Stand. 66, 211–220.PubMedGoogle Scholar
  21. Tharakan, J. P., Chau, P. C. (1986a) Biotechnol. Bioeng. 28, 1064–1071.PubMedCrossRefGoogle Scholar
  22. Tharakan, J. P., Chau, P. C. (1986b) Biotechnol. Bioeng. 28, 329–342.PubMedCrossRefGoogle Scholar
  23. Thayer, P. S. (1973) in Tissue Culture Methods and Applications (Kruse, P. K., and Patterson, M. K., eds.) pp 345–351, Academic Press, London.Google Scholar
  24. Tolbert, W. R., Srigley, W. R., and Prior, C. P. (1988) in Animal Cell Biotechnology, Vol. 3, (Spier, R. E., and Griffiths, J. B., eds.) pp. 373–393, Academic Press, London.Google Scholar
  25. Tyo, M. A., Bulbulian, B. J., Menken, B. Z., and Murphy, T. J. (1988) in Animal Cell Biotechnology, Vol. 3, (Spier, R. E., and Griffiths, J. B., eds.) pp. 357–371, Academic Press, London.Google Scholar
  26. Varecka, R., and Scheirer, W. (1987) Dev. Biol. Stand. 66, 267–272.Google Scholar

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© Stockton Press 1990

Authors and Affiliations

  • Cristina Glad
  • Inge Nilsson

There are no affiliations available

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