|
KMID : 0545120010110030497
|
|
Journal of Microbiology and Biotechnology
2001 Volume.11 No. 3 p.497 ~ p.503
|
|
|
Removal and Inactivation of Viruses during Manufacture of a High Purity Antihemophilic Factor VIII Concentrate from Human Plasma
|
|
KIM, IN SEOP
CHOI, YONG WOON/LEE, SUNG RAE/WOO, HANG SANG/LEE, SOUNGMIN
|
|
|
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 antihemophilic factor Ⅷ (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 Ⅷ 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 7.89log_10 TCIDS_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 factors of 2.32, 2.49, 2.60, and 1.33, respectively. Lyophilization was an effective step in inactivating nonenveloped viruses rather than enveloped viruses, where the log reduction factors of BHV, BVDV, EMCV, 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 ≥11.12, ≥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.
|
|
|
KEYWORD
|
|
|
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|