Abstract
With particular regards to the hepatitis A virus (HAV), a terminal dry-heat treatment (100°C for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate. The loss of factor IX activity during dry-heat treatment was of about 3%, as estimated by a clotting assay. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor IX compared with those of the factor IX before dry-heat treatment. The dry-heat-treated factor IX was stable for up to 24 months at 4°C. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV and murine encephalomyocarditis virus (EMCV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Porcine parvovirus (PPV) and bovine herpes virus (BHV) were potentially sensitive to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were ≥5.60 for HAV, ≥6.08 for EMCV, 2.64 for PPV, and 3.59 for BHV. These results indicate that dry-heat treatment improves the virus safety of factor IX concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of nonlipid enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.
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References
O'Connell, N. M. (2003) Factor XI deficieney-from molecular genetics to clinical management.Blood Coagul. Fibrinolysis 14 Suppl 1: S59-S64.
Berkman, S. A. (1988) Infectious complications of blood transfusion.Blood Rev. 2: 206–210.
Mosley, J. W. and J. Rakela (1999) Foundling viruses and transfusion medicine.Transfusion 39: 1041–1044.
Klein, H. G. (2005) Pathogen inactivation technology: cleansing the blood supply.J. Intern. Med. 257: 224–237.
Tabor, E. (1999) The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1.Transfusion 39: 1160–1168.
Robertson, B. H. and D. D. Erdman (2000) Nonenveloped viruses transmitted by blood and blood products.Dev. Biol. Standard. 102: 29–35.
Morgenthaler, J. J. (2000) New development in plasma fractionation and virus inactivation.Vox Sang. 78 Suppl 2: 217–221.
Laub, R. and P. Strengers (2002) Parvovirus and blood products.Pathol. Biol. (Paris) 50: 339–348.
Burnouf, T. and M. Radosevich (2000) Reducing the risk of infection from plasma products: specific preventative strategies.Blood Rev. 14: 94–110.
Robinson, S. M., H. Schwinn, and A. Smith (1992) Clotting factors and hepatitis A.Lancet 340: 1465.
Chudy, M., I. Budek, B. Keller-Stanislawski, K. A. McCaustland, S. Neidhold, B. H. Robertson, C. M. Nubling, R. Seitz, and J. Lower (1999) A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool.J. Med. Virol. 57: 91–99.
Lawlor, E., S. Graham, E. Davidson, P. L. Yap, C. Cunningham, H. Daly, and I. J. Temperley (1996) Hepatitis A transmission by factor IX concentrates.Vox Sang. 71: 126–128.
Andrewes, C. (1989)Andrewes' Viruses of Vertebrates. pp. 120–145. Balliere Tindal, London, UK.
Kim, I. S., Y. W. Choi, S. R. Lee, and H. M. Sung (2004) Cold ethanol fractionation and heat inactivation of hepatitis A virus during manufacture of albumin from human plasma.Biotechnol. Bioprocess Eng. 9: 57–60.
Roberts, P. L. and H. Hart (2000) Comparison of the inactivation of canine and bovine parvovirus by freezedrying and dry-heat treatment in two high purity factor VIII concentrates.Biologicals 28: 185–188.
Arrighi, S., R. Rossi, M. G. Borri, V. Lesnikov, M. Lesnikova, E. Franco, M. Divizia, M. E. de Santis, and E. Bucci (1995) “In vitro” and in animal model studies on a double virus-inactivation factor VIII concentrate.Thromb. Haemost. 74: 868–873.
Powell J. S., M. Bush, J. Harrison, C. Abildgaard, E. Vosburgh, A. R. Thompson, and D. Hurst (2000) Safety and efficacy of solvent/detergent-treated antihaemophilic factor with an added 80°C terminal dry heat treatment in patients with haemophilia A.Haemophilia 6: 140–149.
International Conference on Harmonisation (1998) Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin; availability.Fed. Regist. 63: 51074–51084.
Kim, I. S., Y. W. Choi, S. R. Lee, Y. Kang, K. M. Lee, D. H. Park, H. S. Woo, and S. Lee (2002) Removal and inactivation of hepatitis A virus during manufacture of urokinase from human urine.Biotechnol. Bioprocess Eng. 7: 340–346.
Kim, I. S., Y. W. Choi, and S. R. Lee (2004) Optimization and validation of a virus filtration process for efficient removal of viruses from urokinase solution prepared from human urine.J. Microbiol. Biotechnol. 14: 140–147.
Kärber, J. (1931) Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche.Arch. Exp. Pathol. Pharmakol. 162: 480–483.
Gummadi, S. N. (2003) What is the role of thermodynamics on protein stability?Biotechnol. Bioprocess Eng. 8: 9–18.
Kim, I. S., H. G. Eo, C. W. Park, C. E. Chang, and S. Lee (2001) Removal and inactivation of human immunodeficiency virus (HIV-1) by cold ethanol fractionation and pasteurization during the manufacture of albumin and immunoglobulins from human plasma.Biotechnol. Bioprocess Eng. 6: 25–30.
Carpenter, J. F., M. J. Pikal, B. S. Chang, and T. W. Randolph (1997) Rational design of stable lyophilized protein formulations: some practical advice.Pharm. Res. 14: 969–975.
Murgatroyd, K. (1997) The freeze drying process. pp. 1–58. In: P. Cameron (eds.):Good Pharmaceutical Freeze-Drying Practice. Interpharm Press, Buffalo Grove, IL, USA.
Dichtelmuller, H., D. Rudnick, B. Breuer, R. Kotitschke, M. Kloft, A. Darling, E. Watson, B. Flehmig, S. Lawson, and G. Frosner (1996) Improvement of virus safety of a S/D-treated factor VIII concentrate by additional dry heat treatment at 100°C.Biologicals 24: 125–130.
Kim, I. S., Y. W. Choi, S. R. Lee, H. S. Woo, and S. Lee (2001) Removal and inactivation of viruses during manufacture of a high purity antihemophilic factor VIII concentrate from human plasma.J. Microbiol. Biotechnol. 11: 497–503.
Kim, I. S. (2003) Comparative inactivation of Hepatitis A virus and Murine Encephalomyocarditis virus to various inactivation processes.Kor. J. Microbiol. 39: 242–247.
Kim, I. S., Y. W. Choi, S. R. Lee, M. S. Lee, K. H. Huh, and S. Lee (2001) Removal and inactivation of hepatitis A virus during manufacture of a high purity antihemophilic factor VIII concentrate from human plasma.J. Microbiol. 39: 67–73.
Boschetti, N., I. Niederhauser, C. Kempf, A. Stuhler, J. Lower, and J. Blumel (2004) Different susceptibility of B19 virus and mice minute virus to low pH treatment.Transfusion 44: 1079–1086.
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Shin, J.S., Choi, Y.W., Sung, H.M. et al. Enhanced virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate by dry-heat treatment. Biotechnol. Bioprocess Eng. 11, 19–25 (2006). https://doi.org/10.1007/BF02931863
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DOI: https://doi.org/10.1007/BF02931863