A collaborative study to establish the 6th International Standard for factor VIII concentrate

A study was carried out to replace the 5(th) WHO International Standard (IS ) for factor VIII concentrate. because of depletion of stocks. Two candidat e concentrates (X and Y) were assayed as potential replacements against the 5(th) IS for FVIII concentrate. in a collaborative study involving 33 labo ratories. Collaborators were asked to use the ISTH/SSC recommendations. inc luding pre-dilution of concentrates in FVIII deficient plasma in their assa ys. Several laboratories performed more than one assay method and altogethe r there were 21 sets of assays with the one-stage method, 6 with the two-st age method and 26 with the chromogenic method. There was good agreement bet ween laboratories using each method for the comparison of concentrates X an d Y against the 5(th) IS, but the overall potencies by one-stage and chromo genic methods each differed by approximately 5% from the overall mean. with the chromogenic potency approximately 10% higher than the one-stage. Inter -laboratory agreement was slightly better for concentrate Y than X, and sta bility studies indicated that Y was more stable than X. After considering a ll the information, together with comments from participants and from the F VIII/FIX Subcommittee of the ISTH/SSC, candidate Y (NIBSC code [97/616]), w as proposed and accepted in October, 1998, by the Expert Committee on Biolo gical Standardisation of the World Health Organisation to be the 6(th) Inte rnational Standard for Factor VIII Concentrate: with an assigned potency of 8.5 IU/ampoule.