EFFECT OF TERMINAL (DRY) HEAT-TREATMENT ON NONENVELOPED VIRUSES IN COAGULATION-FACTOR CONCENTRATES

Terminal dry heat treatment effectively inactivated hepatitis A virus (HAV) and canine parvovirus added to high-purity factor VIII. After 24 h at 80 degrees C, HAV infectivity was reduced by greater than or equ al to 4.3 log(10) TCID50, as measured in a newly developed infectivity assay. The same reduction in virus titer was achieved after 2 h and b efore 6 h at 90 degrees C. Inactivation of hepatitis A virus was also seen in the freeze-drying step prior to heat treatment with an approxi mately 2.0 log(10) reduction in titer. Similar results were obtained w ith a high-purity factor IX concentrate. Canine parvovirus was also in activated at both temperatures, with residual infectivity being undete cted after 48 h at 80 degrees C or 10 h at 90 degrees C. Canine parvov irus was not affected by lyophilisation. Canine parvovirus measurement s by PCR did not reflect the levels of infectivity measured by the tis sue-culture-based method. The addition of the terminal dry heat treatm ent to solvent/detergent could effectively eliminate the potential con tamination of solvent/detergent-treated coagulation factor concentrate s by non-lipid-enveloped viruses. However, careful evaluation for any increased induction of non-antigens for factor VIII, as a consequence of such treatment, is needed before use in patients can be recommended .