Factor VIII Bypassing Activity (FEIBA) assays: standardization and development of the 1st NIBSC Working Standard for FEIBA - results from a collaborative study

Summary Factor‐Eight‐Inhibitor‐Bypassing‐Activity (FEIBA) is a bypassing‐agent used to control spontaneous bleeding or cover surgical interventions in Haemophiliacs who develop neutralizing antibodies against FVIII/FIX. The market lot‐release of FEIBA is dependent on specific clot‐based assays, carried out by both the manufacturer and regulatory authorities, relative to manufacturer's in‐house standards, which are produced on a small‐scale and are replaced frequently. We sought to standardize the FEIBA assay by developing a FEIBA primary standard which would be internationally available in sufficiently large quantities, with a predicted lifetime of many years. A collaborative study involving the manufacturer and three regulatory authorities, was carried out in which a candidate material, sample B (06/172), was calibrated by assays relative to the manufacturer's in‐house FEIBA standards (C and D). All laboratories used their routine validated methods (16 APTT‐assays, 8 ACTIN‐FS‐assays and 27 DAPTTIN‐assays). Intra‐laboratory geometric coefficients of variation (GCVs) for candidate B ranged from 3% to 29% (GCVs