A SOLVENT DETERGENT TREATED PASTEURIZED AND HIGHLY PURIFIED FACTOR-VIII CONCENTRATE/

In an assessment of the risks of virus transmission by clotting concen trates it is clear that the currently practised procedures for virus i nactivation are not equally effective against all types of viruses; ne ither a pasteurisation nor the solvent detergent (S/D) process alone a re adequate enough to inactivate viruses that are strongly resistant t o heat and organic solvents. In this context, human parvovirus B19 and hepatitis A virus (HAV) are of particular concern. In order to improv e this situation which still poses a risk to the haemophiliac patients , a more effective pasteurisation process has been developed that cou ld be easily applied to an already well established factor VIII (FVIII ) process in addition to the S/D-treatment. Experiments using temperat ures above 60 degrees C were performed prompted by two recent publicat ions, which demonstrate that HAV becomes instable at temperatures exce eding 62 degrees C. It is the purpose of this paper to present the fol lowing progress: -achievement of a pasteurisation procedure for FVIII at 63 degrees C for 10 h with no discernible change in the structure o f the factor VIII/von Willebrand factor (FVIII/VWF) complex owing to a newly developed composition of stabilizers; -application of this past eurisation procedure to a purified FVIII fraction that has already bee n submitted to a S/D-treatment: Doing so, two independent virus inacti vation steps are performed as previously recommended by the Internatio nal Association of Biological Standardization (IABS). -Introduction of a second purification step on an anion exchange resin, achieving an a dditional virus reduction over the presently manufactured FVIII prepar ation. Numerous animal studies proved the double virus-inactivated FVI II concentrate to be well-tolerated and without side-reactions. The ef fectivity of the 63 degrees C heating step against different types of non-enveloped and enveloped viruses is published elsewhere.