Journal of Microbiology

The Microbiological Society of Korea (한국미생물학회)
권호 표지

Removal and Inactivation of Hepatitis A Virus during Manufacture of a High Purity Antihemophilic Factor VIII Concentrate from Human Plasma

  • Kim, In-Seop (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Park, Yong-Woon (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Lee, Sung-Rae (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Lee, Mahl-Soon (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Huh, Ki-Ho (Technical Operations Service, Greencross Plasma Derivatives Corp.) ;
  • Lee, Soungmin (Technical Operations Service, Greencross Plasma Derivatives Corp.)
  • Published : 2001.03.01
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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 (TCID$\_$50/) 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 far removal of HAV with the log reduction factor of $\geq$4.3. 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 lag reduction factor, $\geq$10.5, achieved for tile entire manufacturing process was several magnitudes greater than the potential HAV load of current plasma pools.

Keywords

References

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