IN-VITRO AND IN ANIMAL-MODEL STUDIES ON A DOUBLE VIRUS-INACTIVATED FACTOR-VIII CONCENTRATE

To improve the safety of plasma derived factor VIII (FVIII) concentrat e, we introduced a final super heat treatment (100 degrees C for 30 mi n) as additional virus inactivation step applied to a lyophilized, hig hly purified FVIII concentrate (100 IU/mg of proteins) already virus i nactivated using the solvent/detergent (S/D) method during the manufac turing process. The efficiency of the super heat treatment was demonst rated in inactivating two non-lipid enveloped viruses (Hepatitis A vir us and Poliovirus 1). The loss of FVIII procoagulant activity during t he super heat treatment was of about 15%, estimated both by clotting a nd chromogenic assays. No substantial changes were observed in physica l, biochemical and immunological characteristics of the heat treated F VIII concentrate in comparison with those of the FVIII before hear tre atment.