Summary
Seven laboratories estimated factor VIII coagulant activity in recombinant B-domain-deleted
(ReFacto) and plasma-derived FVIII concentrates (Octonativ-M) using chromogenic methods
relative to the WHO 6th International Standard FVIII Concentrate (WHO 6th IS), European
Pharmacopoeia BRP#2 (EP#2) and the ReFacto Laboratory Standard (RLS). Significantly
higher estimates were obtained for all batches of product when calculated relative
to the RLS in comparison with estimates vs WHO 6th IS and EP#2. Mean estimates for
two batches of ReFacto product vs the RLS were within 10% of the labelled potency
whereas estimates vs WHO 6th IS and EP#2 ranged from 21 to 31% lower than the label.
Conversely, mean estimates for Octonativ-M relative to WHO 6th IS and EP#2 were within
10% of the label whereas the mean estimate vs RLS was 117% of label. Mean estimates
for the ReFacto product, vs the WHO 6th IS and EP#2, varied considerably between the
different chromogenic kits whereas estimates vs the RLS showed good agreement between
kits. Mean estimates for the RLS vs 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 results are consistent
with ReFacto and full-length FVIII responding differently to variations in assay methodology
and also indicate that the assigned value on the RLS may be too high. Since this study
the unitage on the RLS has been adjusted to effectively increase the amount of ReFacto
in the product by 20%.
Keywords
Factor VIII - Haemophilia A - chromogenic assays