Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Removal and Inactivation of Viruses during Manufacture of a High Purity Antihemophilic Factor VII Concentration from Human Plasma

  • Kim, In-Seop (Technical Operations Service, Green Cross Plasma Derivatives Co.) ;
  • Choi, Yong-Woon (Technical Operations Service, Green Cross Plasma Derivatives Co.) ;
  • Lee, Sung-Rae (Technical Operations Service, Green Cross Plasma Derivatives Co.) ;
  • Woo, Hang-Sang (Technical Operations Service, Green Cross Plasma Derivatives Co.) ;
  • Lee, Soung-Min (Technical Operations Service, Green Cross Plasma Derivatives Co.)
  • Published : 2001.06.01
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Abstract

The purpose of this study was to examine the efficacy and mechanism of the cryo-precipitation, solvent/detergent (S/D) treatment, monoclonal anti-FVIIIc antibody (mAb) column chromatography, Q-Sepharose column chromatography, and lyophilization involved in the manufacture of antithemophilic factor VII(GreenMono) from human plasma, in the removal and/or inactivation of blood-borne 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 all selected for this study. BHV and EMCV were effectively partitioned from a factor VII during the cryo-precipitation with a log reduction factor of 2.83 and 3.24, respectively. S/D treatment using the organic solvent, tri(n-butyl) phosphate (TNBP), and the detergent, Triton X-100, was a robust and effective step in inactivating enveloped viruses. The titers of BHV and BVDV were reduced from the initial titer of 8.85 and $7.89{log_10} {TCID_50}$, respectively, reaching undetectable levels within 1 min of the S/D treatment. The mAb chromatography was the most effective step for removing nonenveloped viruses, EMCV and PPV, with the log reduction factors of 4.86 and 3.72, respectively. Q-Sepharose chromatography showed a significant efficacy for partitioning BHV, BVDV, EMCV, and PPV with the log reduction the log reduction factors of 2.32, 2.49, 2.60, and 1.33 respectively. Lyophilization was an effective step in inactivating g nonenveloped viruses rather than enveloped viruses, where the log reduction factors of BHV, BVDV, DMCV, and PPV were 1.41, 1.79, 4.76, and 2.05, respectively. The cumulative log reduction factors of BHV, BVDV, EMCV, and PPV were ${\geqq}$11.12, ${\geqq}$7.88, 15.46, and 7.10, respectively. These results indicate that the production process for GreenMono has a sufficient virus-reducing capacity to achieve a high margin of the virus safety.

Keywords

References

  1. Thromb. Haemost. v.67 Treatment of hemophilia A with a highly purified factor Ⅷ concentrate prepared by Anti-FⅧc immunoaffinity chromatography Addiego, Jr. J. E.;E. Gomperts;S. Liu;P. Bailey;S. G. Courter;M. L. Lee;G. G. Neslund;H. S. Kingdon;M. J. Griffith
  2. Blood Rev. v.2 Infectious complications of blood transfusion Berkman, S. A.
  3. Dev. Biol. Stand. v.74 The effect of freeze-drying on the potency and stability of live varicella virus vaccine Bennett, P. S.;R. Z. Maigetter;M. G. Olson;P. J. Provost;E. M. Scattergood;T. L. Schfield
  4. 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.)
  5. Vox Sang. v.67 no.SUP.1 Removal and inactivation of hepatitis A virus (HAV) during processing of factor Ⅷ concentrates Hamman, J.;J. Zou;B. Horowitz
  6. 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
  7. Yale J. Med. v.63 Blood protein derivative viral safety: Observations and analysis Horowitz, B.
  8. Vox Sang. v.74 no.SUP.1 Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma Horowitz, B.;A. Lazo;H. Grossberg;G. Page;A. Lippin;G. Swan
  9. Lancet v.2 Virus safety of solvent/detergent treated antihaemophiliac factor concentrates Horowitz, M. S.;C. Rooks;B. Horowitz;M. W. Hilgartner
  10. J. Med. v.330 Hemophilia A. N. Engl. Hoyer, L. W.
  11. Federal Register v.63 Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin International Conference on Harmonisation
  12. Arch. Exp. Path. Pharmak. v.162 Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche Karber, J.
  13. J. Microbiol. Biotechnol. v.9 Large-scale culture of hepatitis A virus in human diploid MRC-5 cells and partial purification of the viral antigen for use as a vaccine Kim, H.-S.;Y.-J. Chung;Y.-J. Jeon;S.-H. Lee
  14. J. Microbiol. Biotechnol. v.10 Partitioning and inactivation of viruses by cold ethanol fractionation and pasteurization during manufacture of albumin from human plasma Kim, I. S.;H. G. Eo;C. E. Chang;S. 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 Ⅷ concentrate Kim, I. S.;Y. W. Choi;H. S. Woo;C. E. Chang;S. Lee
  16. J. Med. Virol. v.43 Removal/neutralization of hepatitis A virus during manufacture of high purity, solvent/detergent factor Ⅷ concentrate Lemon, S. M.;P. C. Murphy;A. Smith;J. Zou;J. Hammon;S. Robinson;B. Horowitz
  17. Virology(3rd ed.) Levy, J. A.;H. Fraenkel-Conrat;R. A. Owens
  18. Vox Sang. v.64 Clinical evaluation of viral safety of coagulation factor Ⅷ and Ⅸ concentrates Mannucci, P. M.
  19. Transfusion v.39 Foundling viruses and transfusion medicine Mosley, J. W.;J. Rakela
  20. 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. Bernhardt;J. Hilfenhause
  21. 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
  22. Lancet v.1 Sterilization of hepatitis and HTLV Ⅲ viruses by exposure to Tri-n-Butyl phosphate and sodium cholate Prince, A. M.;B. Horowitz;B. Brotman
  23. Vox Sang. v.72 Human parvovirus B19 and blood products Prowse, C.;C. A. Ludlam;P. L. Yap
  24. Rev. Med. Virol. v.6 Virus safety of plasma products Roberts, P.
  25. 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
  26. Curr. Stud. Hematol. Blood Transfus. v.56 Overview of viruses relevant to blood transfusion Schilt, U.
  27. 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