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- Solvent/Detergent Inactivation and Chromatographic Removal of Human Immunodeficiency Virus During the Manufacturing of a High Purity Antihemophilic Factor Ⅷ Concentrate
- In Seop Kim , Yong Woon Choi , Hang Sang Woo , Chong E. Chang , Soungmin Lee
- J. Microbiol. 2000;38(3):187-191.
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Abstract
- A validation study was conducted to determine the efficacy of solvent/detergent (S/D) inactivation and Q-Sepharose column chromatographic removal of the human immunodeficiency virus (HIV) during the manufacturing of a high purity antihemophilic factor VIII (GreenMono) from human plasma. S/D treatment using the organic solvent, tri (n-butyl) phosphate, and the detergent, Triton X-100, was a robust and effective step in eliminating HIV-1. The HIV-1 titer was reduced from an initial titer of 8.3 log 10 TCID 50 to undetectable levels within one minute of S/D treatment. HIV-1 was effectively partitioned from factor VIII during Q-Sepharose column chromatography with the log reduction factor of 4.1. These results strongly assure the safety of GreenMono from HIV.
- Removal and Inactivation of Hepatitis A Virus during Manufacture of a High Purity Antihemophilic Factor VIII Concentrate from Human Plasma
- In Seop Kim , Yong Woon Choi , Sung Rae Lee , Mahl Soon Lee , Ki Ho Huh , Soungmin Lee
- J. Microbiol. 2001;39(1):67-73.
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Abstract
- A validation study was conducted to evaluate the efficacy and mechanism of the cryo-precipitation, monoclonal anti-FVIIIc antibody (mAb) chromatography, Q-Sepharose chromatography, and lyophilization steps involved in the manufacture of high purity factor VIII (GreenMono) from human plasma, in the removal and/or inactivation of hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and subjected to scale-down processes mimicking the manufacture of the high purity factor VIII concentrate. Samples were collected at each step and immediately titrated using a 50% tissue culture infectious dose (TCID50) and then the virus reduction factors were evaluated. HAV was effectively partitioned from factor VIII during cryo-precipitation with the log reduction factor of 3.2. The mAb chromatography was the most effective step for removal of HAV with the log reduction factor of ³4.3. HAV infectivity was not detected in the fraction of factor VIII, while most of HAV infectivity was recovered in the fractions of flow through and wash during mAb chromatography. Q-Sepharose chromatography showed the lowest efficacy for partitioning HAV with the log reduction factor of 0.7. Lyophilization was an effective step in inactivating HAV with the log reduction factor of 2.3. The cumulative log reduction factor, ³10.5, achieved for the entire manufacturing process was several magnitudes greater than the potential HAV load of current plasma pools.
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