A multi-centre collaborative study on the potency estimation of ReFacto

Area of Science:

• Biotechnology
• Clinical Chemistry
• Pharmacology

Background:

• Accurate quantification of factor VIII (FVIII) coagulant activity is crucial for effective hemophilia treatment.
• Chromogenic assays are widely used but can be influenced by the reference standard employed.
• Recombinant FVIII concentrates (ReFacto) and plasma-derived FVIII (Octonativ-M) may exhibit differential responses in assays.

Purpose of the Study:

• To compare the accuracy of factor VIII (FVIII) concentrate estimations using different reference standards.
• To evaluate the performance of the ReFacto Laboratory Standard (RLS) against international standards (WHO 6th IS, EP#2).
• To assess assay variability for recombinant and plasma-derived FVIII concentrates.

Main Methods:

• Seven laboratories performed chromogenic assays to estimate FVIII coagulant activity.
• Assays utilized recombinant (ReFacto) and plasma-derived (Octonativ-M) FVIII concentrates.
• Estimations were made relative to three reference standards: WHO 6th IS, EP#2, and RLS.

Main Results:

• Estimates for ReFacto were significantly higher when using the RLS compared to WHO 6th IS and EP#2.
• ReFacto estimates using RLS were within 10% of labeled potency, while estimates using WHO 6th IS/EP#2 were 21-31% lower.
• Octonativ-M estimates were within 10% of label using WHO 6th IS/EP#2, but 117% of label using RLS.

Conclusions:

• The ReFacto Laboratory Standard (RLS) offers more consistent estimates for recombinant FVIII concentrates.
• Recombinant and plasma-derived FVIII may respond differently to assay methodologies and reference standards.
• The initial assigned value of the RLS was likely too high, leading to adjusted unitage post-study.