DETERMINATION OF ADEQUATE MOISTURE-CONTENT FOR EFFICIENT DRY-HEAT VIRAL INACTIVATION IN LYOPHILIZED FACTOR-VIII BY LOSS ON DRYING AND BY NEAR-INFRARED SPECTROSCOPY

A requirement for a minimal threshold level of moisture in order for e fficient virus inactivation to occur during dry heat treatment of free ze-dried coagulation factor concentrates is described. Techniques used to determine moisture content during heating were Loss on Drying and Karl Fischer. The Loss on Drying was suspected to have occasional erro rs as a result of sample preparation being influenced by interference from atmospheric moisture. Therefore, a non-invasive, non-destructive method for determination of residual moisture content using near infra red spectrometry(NIR) was developed for freeze-dried antihaemophilic f actor (AHF). Calibration equations were determined against Loss on Dry ing and Karl Fischer assay methods and these equations evaluated for t he predictive efficiency. Both Loss on Drying and NIR were used to eva luate the effect of moisture content on the efficiency of virus inacti vation by dry heat at 80 degrees C. A minimum level of moisture of gre ater than 0.7%, as determined by Loss on Drying, was necessary for a v irus reduction in the magnitude of 4 log(10) for hepatitis A virus, po rcine parvovirus and pseudorabies virus. (C) 1998 The International As sociation of Biological Standardization.