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Industrial scale production of Β-interferon

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Bioprocesses Including Animal Cell Culture

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 37))

Abstract

The first part of the survey is dedicated to the current status of the large scale production of Β-IFN, intended for extensive and significant clinical trials. In particular, the methods employed for the growth of human foreskin fibroblasts and the induction and purification of the active molecule are reviewed.

The second part is dedicated to the detailed description of the only plant operating in Italy, producing clinical grade IFN. Special emphasis is given to the control methodologies adopted for the registration of the product.

Finally, some consideration is given to the present state of the art and the future trends in the field of Β-IFN production.

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Abbreviations

Con-A:

concanavaiin-A

CPG:

controlled pore glass

DMEM:

Dulbecco's modified Earle medium

EG:

ethylen glycol

FBS:

fetal calf serum

HEPA:

high efficiency particulate air

IFN:

interferon

IU:

international unit

pCO2 :

dissolved carbon hydroxide pressure

pO2 :

dissolved oxigen pressure

PDL:

population doubling level

RB:

roller bottle

SF:

spinner flask

T:

temperature

References

  1. Youngner, J. S., Stinebring, W. R., Taube, S. E.: Virology 27, 541 (1965)

    Article  PubMed  Google Scholar 

  2. Vilcek, J., Rossman, T. G., Varacalli, F.: Nature 222, 682 (1969)

    PubMed  Google Scholar 

  3. Vilcek, J.: Ann. N.Y. Acad. Sci. 173, 390 (1970)

    Google Scholar 

  4. Tan, Y. H., Armstrong, J. A., Ke, J. H., Ho, M.: Proc. Natl. Acad. Sci. U.S.A. 67, 464 (1970)

    PubMed  Google Scholar 

  5. Havell, E. R., Vilcek, J.: Antimicro. Ag. Chemother. 2, 476 (1972)

    Google Scholar 

  6. Billiau, A., Joniau, M., De Somer, P.: J. Gen. Virol. 19, 1 (1973)

    PubMed  Google Scholar 

  7. Committee on Interferon Nomenclature Nature, 286, 110 (1980)

    Google Scholar 

  8. Jacobs, J. P.: Serially-propagated human diploid cell: a synopsis of the present position concerning their use for producing viral vaccines and interferon, in: Develop. Biol. Standard. 42, (ed. Inter. Assoc. Biol. Standard.) p. 13, Basel, S. Karger 1978

    Google Scholar 

  9. Derynck, R., Content, J., De Clercq, E., Volckaert, G., Tavernier, J., Devos, R., Fiers, W.: Nature, 285, 542 (1980)

    Google Scholar 

  10. Taniguchi, T., Ohno, S., Takaoka, C.: Expression of the cloned genes for human interferon Β 1 in E. coli and cultural mouse cells, in: Interferons, UCLA Symposia on molecular and cellular biology, 25 (eds. Merigan, T. and Friedman, R.) p. 15, New York, Academic Press 1982

    Google Scholar 

  11. Goeddel, D. V., Shepard, H. M., Yelverton, E., Leung, D., Crea, R.: Nucleic Acids Res. 8, 4057 (1980)

    PubMed  Google Scholar 

  12. Ohno, S., Taniguchi, T.: Nucleic Acid Res. 10, 967 (1982)

    PubMed  Google Scholar 

  13. Utsumi, J., Itzuka, M., Kobayashi, S.: J. of Interf. Research 4, 9 (1984)

    Google Scholar 

  14. Jankowsky, W. J., Davey, M. W., O'Malley, J. A., Sulkowsky, E., Carter, A.: J. Virol. 16, 1124 (1975)

    PubMed  Google Scholar 

  15. Gheysen, D., Fiers, W.: J. Mol. Appl. Genet. 1, 385 (1982)

    PubMed  Google Scholar 

  16. Cannaani, D., Berg, P.: Proc. Natl. Acad. Sci. U.S.A. 79, 5166 (1982)

    PubMed  Google Scholar 

  17. McCormik, F., Trahey, M., Innis, M., Dieckmann, B., Ringold, G.: Mol. and Cell Biol. Jan., 166 (1984)

    Google Scholar 

  18. Pitha, P. M., Reyes, G. R., Raj, N. B. K., Hayward, G. S.: Expression of human Β-interferon gene in heterologous cells, in: Interferons, UCLA Symposia on Molecular and Cellular Biology, 25 (eds. Merigan, T. and Friedman, R.) p. 41, New York, Academy Press 1982

    Google Scholar 

  19. Van Brunt, J.: Biotechnology 4, 835 (1986)

    Article  Google Scholar 

  20. Billiau, A., De Somer, P.: Clinical use of interferons in viral infections, in: Interferon and interferon inducers: Clinical application (ed. Stringfellow, D. A.) p. 114, 1980

    Google Scholar 

  21. Obert, H. J.: Clinical Trials conducted with beta-interferon. The biology of the Interferon in Germany, in: The Biology of the Interferon System (eds. De Maeyer, E., and Schellekens, H.) p. 469, Amsterdam, New York, Oxford, Elsevier Science Publishers 1983

    Google Scholar 

  22. Suzuki, H.: Effect of human fibroblast interferon (Hu IFN Β) on Hbc antigen-positive chronic active hepatitis, in: Proceedings of the International Symposium on Interferons (ed. Kiishida, T.) p. 259, Japan Convention Services Inc., Osaka Branch 1983

    Google Scholar 

  23. Van Damme, J., Billiau, A.: Large scale production of Human Fibroblast Interferon, in: Methods in Enzymology 78 (ed. Pestka, S.) p. 101, New York, London 1981

    Google Scholar 

  24. Spier, R. E.: Adv. Biochem. Eng. 14, 119 (1980)

    Google Scholar 

  25. Leong, S. S., Horoszewicz, J. S.: Production and preparation of human fibroblast interferon or clinical trials, in: Methods in Enzymology 78 (ed. Pestka, S.) p. 87, New York, London 1981

    Google Scholar 

  26. Skoda, R., Pakos, V., Hörmann, A., SpÄth, O., Johansson, A.: Communicating Vessel Systems for Mass Cell Culture of Anchorage Dependent Cells, in: Develop. Biol. Standard. 42 (ed. Inter. Assoc. Biol. Standard) p. 121, Basel, S. Karger 1978

    Google Scholar 

  27. Obert, H. J., Joester, K. E.: Sources of Interferon for Clinical use: Β-Interferon from Fibroblasts, in: Interferon 4 (eds. Finter, N. B., Oldham, R. K.) p. 89, Amsterdam-New York-Oxford, Elsevier 1985

    Google Scholar 

  28. Kruse, P. F., Mediema, E.: J. Cell. Biol. 27, 273 (1965)

    Article  PubMed  Google Scholar 

  29. Mann, G. F.: PAHO Bulletin VI 33, (1972)

    Google Scholar 

  30. Van Wezel, A.: Nature 216, 64 (1967)

    PubMed  Google Scholar 

  31. Katinger, D., Scheirer, W.: Mass cultivation of mammalian cells in an airlift fermentor, in: Develop. Biol. Standard. 42 (ed. Intern. Ass. Biol. Standard.) p. 111, Basel, S. Karger 1979

    Google Scholar 

  32. Berg, G. J.: An integrated system for large-scale cell culture, in: Develop. Biol. Standard. 60 (ed. Intern. Ass. Biol. Standard.) Basel, S. Karger 1984

    Google Scholar 

  33. Knazek, R. A.: Science 178, 65 (1972)

    Google Scholar 

  34. Knight, E.: Proc. Natl. Acad. Sci. U.S.A. 73, 520 (1967)

    Google Scholar 

  35. Berthold, W., Tan, C., Tan, Y. H.: J. Biol. Chem. 253, 5206 (1978)

    PubMed  Google Scholar 

  36. Heine, J. W., De Ley, M., Van Damme, J., Billiau, A., De Somer, P.: Ann. N.Y. Acad. Sci. 350, 364 (1980)

    Google Scholar 

  37. Friesen, N. J., Stein, S., Evinger, M., Familletti, P. C., Moschera, J., Meienhofer, J., Shively, J., Pestka, S.: Arch. Biochem. Biophys. 206, 432 (1981)

    Article  PubMed  Google Scholar 

  38. Knight, E., Fahey, O.: J. Biol. Chem. 256, 3609 (1981)

    PubMed  Google Scholar 

  39. Novick, D., Eshhar, Z., Gigi, O., Marks, Z., Revel, M., Rubinstein, M.: J. Gen. Virol. 64, 905 (1983)

    PubMed  Google Scholar 

  40. Berg, K., Ogburn, C. A., Paucker, K., Mogensen, K. E., Cantell, K.: J. Immunol. 114, 640 (1975)

    PubMed  Google Scholar 

  41. Hochkeppel, H. K., Menge, V., Collins, J.: Nature 291, 500 (1981)

    Article  PubMed  Google Scholar 

  42. Zoon, K.: Interferon Test Procedure: Points to consider in the production and testing of interferon intended for investigational use in humans, Office of Biologies National Center for Drugs and Biologies, July 28, 1983

    Google Scholar 

  43. Mun, H. NG., Vilcek, J.: Adv. Prot. Chem. 26, 173 (1972)

    Google Scholar 

  44. Edy, V. G., Braude, I. A., De Clercq, E., Billiau, A., De Somer, A.: J. Gen. Virol. 33, 517 (1976)

    PubMed  Google Scholar 

  45. Heine, K. J. W., Billiau, A.: Purification of human fibroblast interferon by adsorption to controlled-pore glass and zinc-chelate chromatography, in: Methods in Enzymology, 78 (ed. Pestka, S.) p. 448, New York, London, 1981

    Google Scholar 

  46. Heine, J. W., Van Damme, J., De Ley, M., Billiau, A., De Somer, P.: J. Gen. Virol. 54, 47 (1981)

    PubMed  Google Scholar 

  47. Edy, V. G., Billiau, A., De Somer, P.: J. Biol. Chem. 252, 5939 (1977)

    PubMed  Google Scholar 

  48. Havell, E. A., Vilcek, J.: Antimicrob. Agents Chemothe. 2, 476 (1972)

    Google Scholar 

  49. Allison, L. M. C., Mann, G. F., Perkins, F. T., Zuckerman, A. J.: J. Biol. Standard. 9, 185 (1981)

    Google Scholar 

  50. Code of Federal Regulations 21: Parts 600–789 Paragraph 630. 13 (C.2). Revised April 1, 1983

    Google Scholar 

  51. WHO Tech. Rep. Ser. 610, 54 (1977)

    Google Scholar 

  52. WHO Tech. Rep. Ser. 658, 313 (1981)

    Google Scholar 

  53. Morandi, M., Stangheilini, L., Valeri, A.: Problems involved in the large-scale production of biological products, such as Β-interferon, using diploid fibroblast cells as substrate, in: Develop. Biol. Standard. 60 (ed. Intern. Ass. Biol. Standard.) p. 405, Basel, S. Karger, 1984

    Google Scholar 

  54. Rubinstein, S., Familletti, P. C., Pestka, S.: J. Virol. 37, 755 (1981)

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Biological Research and Development Sclavo S.p.A., Via Fiorentina 1, 53100, Siena, Italy

    M. Morandi & A. Valeri

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  1. M. Morandi
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  2. A. Valeri
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© 1988 Springer-Verlag

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Morandi, M., Valeri, A. (1988). Industrial scale production of Β-interferon. In: Bioprocesses Including Animal Cell Culture. Advances in Biochemical Engineering/Biotechnology, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0009177

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  • DOI: https://doi.org/10.1007/BFb0009177

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-19004-2

  • Online ISBN: 978-3-540-38899-9

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