Advertisement

Removal and inactivation of human immunodeficiency virus (HIV-1) by cold ethanol fractionation and pasteurization during the manufacturing of albumin and immunoglobulins from human plasma

  • In Seop Kim
  • Ho Gueon Eo
  • Chan Woo Park
  • Chong E. Chang
  • Soungmin Lee
Article

Abstract

Viral safety is a prerequisite for manufacturing clinical albumin and immunoglobulins from human plasma pools. This study was designed to evaluate the efficacy of cold ethanol fractionation and pasteurization (60°C heat treatment for 10 h) for the removal inactivation of human immunodeficiency virus type 1 (HIV-1) during the manufacturing of albumin and immunoglobulins. Samples from the relevant stages of the production process were spiked with HIV-1, and the amount of virus in each fraction was quantified by the 50% tissue culture infectious dose (TCID50). Both fraction IV fractionation and pasteurization steps during albumin processing were robust and effective in inactivating HIV-1, titers of which were reduced from an initial 8.5 log10 TCID50 to undetectable levels. The log reduction factors achieved were ≥4.5 and ≥6.5, respectively. In addition, fraction III fractionation and pasteurization during immunoglobulins processing were robust and effective in eliminating HIV-1. HIV-1 titers were reduced from an initial 7.3 log10 TCID50 to undetectable levels. The log reduction factors achieved in this case were ≥4.9 and ≥5.3, respectively. These results indicate that the process investigated for the production of albumin and immunoglobulins have sufficient HIV-1 reducing capacity to achieve a high margin of safety.

Keywords

albumin immunoglobulins cold ethanol fractionation pasteurization human immunodeficiency virus log reduction value 

References

  1. [1]
    Cohn, E. J., L. E. Strong, W. L. Hughes Jr, D. J. Mulford, J. N. Ashworth, M. Melin, and H. L. Taylor (1946) Preparation and properties of serum and plasma proteins. IV. A system for the separation into fractions of the proteins and lipoprotein components of biological tissues and fluids.J. Am. Chem. Soc. 68: 459–475.CrossRefGoogle Scholar
  2. [2]
    Horowitz, B. (1990) Blood protein derivative viral safety: observations and analysis.Yale J. Med. 63: 361–369.Google Scholar
  3. [3]
    Mosley, J. W. and J. Rakela (1999) Foundling viruses and transfusion medicine.Transfusion 39: 1041–1044.CrossRefGoogle Scholar
  4. [4]
    Berkman S. A. (1988) Infectious complications of blood transfusion.Blood Rev. 2: 206–210.CrossRefGoogle Scholar
  5. [5]
    Schilt, U. (1989) Overview of viruses relevant to blood transfusion.Curr. Stud. Hematol. Blood Transfus. 56: 1–8.Google Scholar
  6. [6]
    Cuthbertson, B., K. G. Reid, and P. R. Foster (1991) Viral contamination of human plasma and procedures for preventing virus transmission by plasma products. pp. 385–435. In: J. R. Harris (eds.).Blood separation and plasma fractionation. Wiley-Liss., NY, USA.Google Scholar
  7. [7]
    Will, R. G., J. W. Ironside, M. Zeidler, S. N. Cousens, K. Estibeiro, A. Alperovitch, S. Poster, M. Pocchiari, A. Hofman, and P. G. Smith (1996) A new varient of Creutzfeldt-Jakob-Disease in the UK.Lancet 347: 921–925.CrossRefGoogle Scholar
  8. [8]
    Erstad, B. L. (1996) Viral infectivity of albumin and plasma protein fraction.Pharmacotherapy 16: 996–1001.Google Scholar
  9. [9]
    Roberts, P. (1996) Virus safety of plasma products.Rev. Med. Virol. 6: 25–38.CrossRefGoogle Scholar
  10. [10]
    Federal Health Office and Paul Ehrlich Institute Federal Office for Sera and Vaccines (1994) Notice on the registration of drugs: requirements for validation studies to demonstrate the virus safety of drugs derived from human blood or plasma.Bundesanzeiger 84: 4742–4744.Google Scholar
  11. [11]
    The European Agency for the Evaluation of Medicinal Products: Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses (CPMP/BWP/268/95).Google Scholar
  12. [12]
    The European Agency for the Evaluation of Medicinal Products: Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on plasma derived medicinal products (CPMP/BWP/269/95 rev 2).Google Scholar
  13. [13]
    The European Agency for the Evaluation of Medicinal Products: Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on quality of biotechnology products: viral safety evaluation of biotechnology products derived from cell Lines of human or animal origin (CPMP/ICH/295/95).Google Scholar
  14. [14]
    International Conference on Harmonisation (1998) Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin; Availability.Federal Resister 63(185): 51074–51084.Google Scholar
  15. [15]
    Oncley, J. L., M. Melin, D. A. Richert, J. W. Cameron, and P. M. Jr. Gross (1949) The separation of the antibodies, isoaggulitinins, prothrombin, plasminogen and β1-lipoprotein into subfractions of human plasma.J. Am. Chem. Soc. 71: 541–550.CrossRefGoogle Scholar
  16. [16]
    Kärber, J. (1931) Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche.Arch. Exp. Path. Pharmak. 162: 480–483.CrossRefGoogle Scholar
  17. [17]
    Morgenthaler, J. J. (1989) Inactivation of viruses and safety of stable plasma products.Beitr. Infusionsther. 24: 33–39.Google Scholar
  18. [18]
    Menache, D. and D. L. Aronson (1985) Measures to inactivate viral contaminants of pooled plasma products.Prog. Clin. Biol. Res. 182: 407–423.Google Scholar
  19. [19]
    Heimburger, N. and H. E. Karges (1989) Strategics to produce virus-safe blood derivatives.Curr. Stud. Hentatol. Blood Transfus. 56: 23–33.Google Scholar
  20. [20]
    Heldebrant, C. M., E. D. Gomperts, C. K. Kasper, J. S. McDougal, A. E. Friedman, D. S. Hwang, E. Muchmore, S. Jordan, R. Miller, E. Sergis-Da-Venport, and W. Lam (1985) Evaluation of two viral inactivation methods for the preparation of safer factor VIII and factor IX concentrates.Transfusion 25: 510–515.CrossRefGoogle Scholar
  21. [21]
    Nowak, T., J.-P. Gregersen, U. Klockmann, L. B. Cummins, and J. Hilfenhaus (1992) Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure.J. Med. Virol. 36: 209–216.CrossRefGoogle Scholar
  22. [22]
    Uemura, Y., Y. H. J. Yang, C. M. Heldebrant, K. Takechi, and K. Yokoyama (1994) Inactivation and elemination of viruses during preparation of human intravenous immunoglobulin.Vox Sang. 67: 246–254.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering 2001

Authors and Affiliations

  • In Seop Kim
    • 1
  • Ho Gueon Eo
    • 1
  • Chan Woo Park
    • 2
  • Chong E. Chang
    • 1
  • Soungmin Lee
    • 1
  1. 1.Technical Operations ServiceGreencross Plasma Derivatives Corp.Yongin City, Kyunggi-DoKorea
  2. 2.GreenCross Vaccine Corp.Yongin City, Kyunggi-DoKorea

Personalised recommendations