Estimation of Nuwiq® (simoctocog alfa) activity using one-stage and chromogenic assays-Results from an international comparative field study

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.

Keywords: Nuwiq®; chromogenic assay; coagulation factor VIII; field study; human-cl rhFVIII; one-stage assay.