A multicenter study on the potency estimation of ReFacto

Abstract number: P1613

Hubbard^* A., Sands^* D., Sandberg† E., Seitz‡ R., Barrowcliffe^* T. W.

†Danish Medicines Agency, Denmark; ^*NIBSC, UK; ‡Paul-Ehrlich-Institut, Germany

Six European control laboratories and one manufacturer participated in a study, under the auspices of the European Medicines Evaluation Agency, on the estimation of factor VIII coagulant activity (FVIII:C) in recombinant B-domain-deleted concentrate (ReFacto, Wyeth Inc) and plasma-derived FVIII concentrate (Octonativ-M, Biovitrum). Potencies were estimated using four chromogenic assay methods (Chromogenix Coatest – kit method and modified version, Chromogenix Coamatic kit, Immunochrom kit), relative to three standards WHO 6th International Standard FVIII Concentrate (WHO 6th IS), European Pharmacopoeia BRP#2 (EP#2) and the ReFacto Laboratory Standard (RLS). No significant differences were found between the mean potencies calculated relative to the WHO 6th IS and EP#2 for all products. However, significantly higher mean estimates were found for all products relative to the RLS together with lower interlaboratory variability for the ReFacto product. Mean estimates for the ReFacto product, relative to the WHO 6th IS and EP#2 standards, obtained using the Coamatic and Immunochrom kits were 15–41% lower than estimates with the Coatest kit whereas estimates relative to the RLS showed good agreement between kits. Mean estimates for the RLS relative to the WHO 6th IS (8.10 IU/vial) and the EP#2 (7.66 IU/vial) were lower than the assigned value of 9.4 IU/vial. The study has highlighted two problems associated with the assay of ReFacto (1) B-domain-deleted FVIII and full-length FVIII behave as ‘’unlike materials in the chromogenic assay method so giving rise to methods-based potency discrepancies when ReFacto is estimated relative to the WHO 6th IS and EP#2, and (2) the overall low mean potencies for ReFacto product when assayed relative to the WHO 6th IS and EP#2 indicated that the assigned value on the RLS may be too high.