Removal/neutralization of hepatitis A virus during manufacture of high purity, solvent/detergent factor VIII concentrate.
Recent reports have suggested an increased risk of type A viral hepatitis in hemophilic patients treated with high purity factor VIII concentrates prepared using ion exchange chromatography coupled with solvent/detergent treatment for inactivation of viruses. To determine the capacity for removal or inactivation of hepatitis A virus during the factor VIII manufacturing process, human plasma and various factor VIII production intermediates were spiked with cell culture-propagated virus and subjected to scaled down conditions mimicking the manufacture of solvent/detergent factor VIII. The combination of antibody-mediated neutralization, cryoprecipitation, anion exchange chromatography, and lyophilization in the absence of sucrose resulted in a minimal reduction of 5.5 to 8.55 log10 in the infectivity of hepatitis A virus.
Lemon
S M
SM
Department of Medicine, University of North Carolina, Chapel Hill 27599-7030.
Murphy
P C
PC
Smith
A
A
Zou
J
J
Hammon
J
J
Robinson
S
S
Horowitz
B
B
D000818:Animals; D000937:Antigen-Antibody Reactions; D002460:Cell Line; D002522:Chlorocebus aethiops; D002848:Chromatography, DEAE-Cellulose / Q000379:methods; D003080:Cold Temperature; D003902:Detergents; D004340:Drug Contamination; D005169:Factor VIII / Q000096:biosynthesis / Q000302:isolation & purification* / Q000592:standards*; D005612:Freeze Drying; D006507:Hepatovirus / Q000302:isolation & purification*; D006801:Humans; D007668:Kidney; D009500:Neutralization Tests; D012997:Solvents; D014462:Ultrafiltration
D003902:Detergents; D012997:Solvents; D005169:Factor VIII