Abstract
BACKGROUND: Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy. FVIII: C can be measured by one-stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability. AIMS: This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq(®) (human-cl rhFVIII, simoctocog alfa), a fourth-generation recombinant human FVIII produced in a human cell line. METHODS: FVIII-deficient plasma was spiked with Nuwiq(®) or Advate(®) at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter- and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed. RESULTS: Forty-nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq(®) :Advate(®) ) of 1.02-1.13. Mean recoveries ranged from 97% to 191% for Nuwiq(®) , and from 93% to 172% for Advate(®) , with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq(®) and from 1.01 to 1.17 for Advate(®) . CONCLUSIONS: Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq(®) in routine laboratory practice, without the need for a product-specific reference standard.