J. Hilfenhaus et al., INACTIVATION OF HEPATITIS-A VIRUS BY PASTEURIZATION AND ELIMINATION OF PICORNAVIRUSES DURING MANUFACTURE OF FACTOR-VIII CONCENTRATE, Vox sanguinis, 67, 1994, pp. 62-66
Hepatitis A virus (HAV) infections have been reported among hemophilia
cs who received factor VIII concentrates which had been purified by io
n-exchange chromatography and treated by the solvent detergent (SD) me
thod. Since the virus inactivation procedure of our manufacturing proc
ess is heat treatment of the stabilized, aqueous protein solution at 6
0 degrees C for 10 h (pasteurization), we investigated whether this me
thod inactivated picornaviruses such as HAV and poliovirus type I, whi
ch we routinely use as a test virus for non-enveloped viruses. HAV was
substantially inactivated by pasteurization but the stabilizers used
in the manufacturing process of the commercial products considerably d
elayed HAV inactivation. Residual infectious HAV was found even after
10 h heat treatment of the stabilized preparation. Thus HAV is more st
able in the presence of stabilizers than poliovirus type 1. Furthermor
e, we studied stage by stage the elimination of poliovirus type 1 by t
he manufacturing procedure of these pasteurized factor VIII concentrat
es. Three other stages of the manufacturing process apart from pasteur
ization eliminated poliovirus by approximately three orders of magnitu
de each. Taking into account this efficient elimination of the picorna
virus poliovirus and the substantial inactivation of HAV by pasteuriza
tion, we conclude that a high margin of safety exists for pasteurized
factor VIII concentrates regarding HAV. This conclusion is supported b
y the fact that no HAV infection has been reported in hemophilia patie
nts treated with pasteurized factor VIII concentrates. Furthermore, in
a retrospective study, none of 95 patients subjected to a long-term t
reatment with pasteurized factor VIII concentrates had developed anti-
HAV seroconversion as a result of this treatment.