Partitioning and Inactivation of Viruses by Cold Ethanol Fractionation and Pasteurization during Manufacture of Albumin from Human Plasma

  • Kim, In-Seop (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Eo, Ho-Gueon (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Chang, Chon-Geun (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Lee, Soung-Min (Technical Operations Service, Greencross Plasma Derivatives Corp.)
  • 발행 : 2000.12.01

초록

The purpose of the present study was to examine the efficacy and mechanism of the fraction IV cold ethanol fractionation and pasteurization ($60^{\circ}C$ heat treatment for 10h) steps, involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of blood-born viruses. A variety of experimental model viruses for human pathogenic viruses, including the Bovine viral diarrhoea virus (BVDV), Bovine herpes virus (BHV), Murine encephalomyocarditis virus (EMCV), and Porcine parvovirus (PPV), were selected for this study. Samples from the relevant stages of the production process were spiked with the viruses, and the amount of virus in each fraction was then quantified using a 50% tissue culture infectious dose ($TCID_{50}$). The mechanism of reduction for the enveloped viruses (BHV and BVDV) during fraction IV fractionation was inactivation rather than partitioning, however, it was partitioning in the case of the non-enveloped viruses (EMCV and PPV). The log reduction factors achieved during fraction IV fractionation were ${\geq}6.9$ BHV, $\geq5.2$ for BBDV, 4.9 for EMC, and 4.0 for PPV. Pasteurization was found to be a robust and effective step in inactivating the enveloped viruses as well as EMCV. The log reduction factors achieved during pasteurization were $\geq7.0$ for BHV, $\geq6.1$ for BVDV, $\geq6.3$ for EMCV, and 1.7 for PPV. These results indicate that the production process for albumin has sufficient virus-reducing capacity to achieve a high margin for virus safety.

키워드

참고문헌

  1. Blood Rev. v.2 Infectious complications of blood transfusion Berkman, S. A.
  2. Biologicals v.26 Inactivation kinetics of model and relevant bloodborne viruses by treatment with sodium hydroxide and heat Borovec, S.;C. Broumis;W. Adcock;R. Fang;E. Uren
  3. Prep. Biochem. Biotechnol. v.30 Human intravenous immunoglobulin preparation and virus inactivation by pasteurization and solvent detergent treatment Chang, C. H.;H. G. Eo;Y. S. Lee;S. K. Chung;J. S. Shin;Y. K. Lah;C. W. Park;J. T. Jung;J. W. Huh;S. M. Lee
  4. J. Am. Chem. Soc. v.68 Prepatation 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 Cohn, E. J.;L. E. Strong;W. L. Hughes, Jr;D. J. Mulford;J. N. Ashworth;M. Melin;H. L. Taylor
  5. Blood separation and plasma fractionation Viral contamination of human plasma and procedures for preventing virus transmission by plasma products Cuthbertson, B.;K. G. Reid;P. R. Foster;J. R. Harris(ed.)
  6. Biologicals v.24 Improvement of virus safety of a S/D-treated factor VIII concentrate by additional dry heat treatment at 100°C Dichtelmuller, H.;D. Rudnock;B. Breuer;R. Kotitschke;M. Kloft;A. Darling;E. Watson;B. Flehmig;S. Lawson;G. Frosner
  7. Pharmacotherapy v.16 Viral infectivity of albumin and plasma protein fraction Erekad, B. L.
  8. J. Microbiol. Biotechnol. v.8 Expression and characterization of recombinant E2 protein of hepatitis C virus by insect cell/baculovirus expression system Han, B. W.;B. Lee;M. K. Min;K. H. Jung
  9. Curr. Stud. Hematol. Blood Transfus v.56 Strategies to produce virus-safe blood derivatives Heimburger, N.;H. E. Karges
  10. Transfusion v.25 Evaluation of two viral inactivation methods for the preparation of safer factor VIII and factor IX concentrates 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;W. Lam
  11. Yale J. Med v.63 Blood protein derivative viral safety: Observations ans analysis Horowitz, B.
  12. Federal Resister v.63 no.185 Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin: Availability International Conference on Harmonisation
  13. Arch. Exp. Path. Pharmak v.162 Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche Karber, J.
  14. J. Microbiol. Biotechnol. v.9 Large-scale culture of hepatitis A virus in human diploid MRC-5 cell and partial purification of the viral antigen for use as a vaccine Kim, H.-S.;Y.-J. Chung;Y.-J. Jeon;S.-H. Lee
  15. J. Microbiol. v.38 Solvent/detergent inactivation and chromatographic removal of human immunodeficiency virus during the manufacturing of a high purity antihemophilic factor YIII concentrate Kim, I. S.;Y. W. Choi;H. S. Woo;C. E. Chang;S. Lee
  16. Virology(3rd ed) Levy, J. A.;H. Fraenkel-Conrat;R. A. Owens
  17. Transfusion v.38 Safety of human albumin as a constituent of biologic therapeutic products McClelland, D. B. L.
  18. Prog. Clin. Biol. Res. v.182 Measures to inactivate viral contaminants of pooled plasma products Menache, D.;D. L. Aronson
  19. Beitr. Infusionsther v.24 Inactivation of viruses and safety of stable plasma products Morgenthaler, J. J.
  20. Transfusion v.39 Founding viruses and transfusion medicine Mosley, J. W.;J. Rakela
  21. J. Med. Virol. v.36 Virus safety of human immunoglobulins: Efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure Nowak, T.;J.-P. Gregersen;U. Klockmann;L. B. Cummins;J. Hilfenhaus
  22. Dev. Biol. Stand. v.81 Inactivation of HIV, HBV, HCV related viruses and other viruses in human plasma derivatives by pasteurization Nowak, T.;M. Niedrig;D. Bernhaedt;J. Hilfenhaus
  23. J. Am. Chem. Soc. v.71 The separation of the antibodies, isoaggulitinins, prothrombin, plasminogen and β₁-lipoprotein into subfractions of human plasma Oncley, J. L.;M. Melin;D. A. Richert;J. W. Cameron;P. M. Jr. Gross
  24. J. Microbiol. Biotechnol. v.9 Purification and characterization of recombinant hepatitis C virus replicase Park, C.;Y. Kee;J. Lee;J. Oh;J. Park;H. Myung
  25. Vox Sang v.72 Human parvovirus B19 and blood products Prowse, C.;C. A. Ludlam;P. L. Yap
  26. Rev. Med. Virol. v.6 Virus safety of plasma products Roberts, P.
  27. Transfusion v.37 Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100°C heat after lyophilization Santagostino, E.;P. M. Mannucci;A. Gringeri;A. Azzi;M. Morfini;R. Musso;R. Santoro;M. Schiavoni
  28. Curr. Stud. Hematol. Blood Transf. v.56 Overview of viruses relevant to blood transfusion Schilt, U.
  29. Intervirology v.23 Characteristics and taxonomy of Parvoviridae Siegl, G.;R. C. Bates;K. I. Berns;B. J. Carter;D. C. Kelly;E. Kurstak;P. Tattersall
  30. Vox Sang v.67 Inactivation and elemination of viruses during preparation of human intravenous immunoglobulin Uemura, Y.;Y. H. Yang;C. M. Heldebrant;K. Takechi;K. Yokoyama