For haemophilia centres, it will be increasingly important to identify the product used for treatment before selecting appropriate assay conditions which will make dialogue between treaters and laboratorians the key to safe and effective monitoring in postinfusion samples. Accurate potency labelling of clotting factor

concentrates is important for dosing of these therapeutics. In addition, potency and specific activity are critical attributes that define a find more particular product. Therefore, potency estimate discrepancies between assay methods have a negative impact on the consistency of production and the efficacy of these concentrates. There are a number of publications describing assay discrepancies for FVIII concentrates, some of which related to one-stage and two-stage clotting assays for intermediate purity and high-purity plasma-derived products [22, 23], whereas others reported clotting and chromogenic assay discrepancies for full-length

recombinant and B domain deleted FVIII [14, 24, 25]. These discrepancies have been ascribed to number of possibilities including the choice of reference standards, diluents used in the assays, source of phospholipids, the activation status of the products, and the presence RAD001 ic50 or absence of von Willebrand factor [26-30]. Studies showed that by assaying ‘like against like’, assay discrepancies could be reduced [16, 20, 14] and the World Health Organization (WHO) selects and establishes international standards (IS) that give the lowest inter-laboratory variability in potency estimates [30, 31]. However, with the variety of available products,

it is difficult to a have a single reference standard that allows for assaying ‘like against like’ for all products. There Thymidylate synthase are several new generation FVIII and FIX products in development, and a new recombinant FIX [32] product as well as a B-domain deleted FVIII were recently licensed [33]. Recently, there have been a number of preliminary publications describing assay discrepancies for these new generation products, with potency disagreement most prominent for the long-acting products. Assay discrepancies described were not restricted to the one-stage clotting and chromogenic assays, but also discrepancies between potencies obtained using different APTT reagents and different chromogenic kits [34-38]. In 2013, the Scientific and SSC of the ISTH published recommendations on potency labelling of factor VIII and factor IX concentrates [7]. These recommendations provide a pathway based on the validity of value assignment relative to the current WHO IS and take into account whether statistically valid bioassays can be obtained by different assay types.