Factor IX  As for FVIII, a FIX concentrate standard was the

first to be established by the WHO for therapeutic materials [12]. Subsequently, an international plasma standard for FIX, together with the other vitamin K-dependent factors II, VII and X, was established by the WHO in 1987 [13]. Most local and commercial learn more plasma standards are now calibrated in IU. Other coagulation factors and inhibitors  The establishment of IS for the other coagulation factors and for inhibitors has followed the same pattern as for FVIII and FIX, with separate standards for plasma and concentrates, where the latter exist. Plasma standards have been established for factors II, V, VII, X, XI and XIII, VWF, fibrinogen, antithrombin, protein C and protein S. Concentrate Standards have been established for factors II, VII, VIIa and X, VWF, thrombin, fibrinogen, antithrombin and protein C. Since the establishment of the first WHO IS for FVIII and FIX concentrates, selleck screening library all plasma-derived and recombinant therapeutic concentrates have been labelled in IU, where 1 IU was originally defined as the amount of analyte in 1ml of pooled, normal plasma. This approach simplifies calculations for replacement dosage and postinfusion recovery and has been remarkably successful

over the last four decades. Potency labelling for FVIII concentrates currently relies on two methods for the quantification of coagulant activity, namely, the one-stage clotting and chromogenic methods, which are preferred for product labelling in the USA and Europe respectively. The choice of FVIII potency method for labelling is irrelevant when both methods agree, but is crucial when there are significant discrepancies 上海皓元 and the products are marketed internationally.

In the past, the labelling of such products (e.g. method-M immuno-purified and the first generation B-domain-deleted products) was managed either by maintaining formulations within the acceptable potency limits for both assay methods, or by implementing the same method for potency labelling when the product was licensed in different countries [14]. However, when licensing authorities adopt different approaches to potency labelling, there is potential for discordance in the IU. For instance, albumin-free formulated B-domain-deleted recombinant FVIII is licensed in the USA as Xyntha (labelled by one-stage clotting assay) and in Europe as ReFacto AF (labelled by chromogenic assay), where 1 IU of the Xyntha product is equivalent to 1.38 IU of the ReFacto AF product. This example is a timely reminder of the problems we currently face with the new modified products. These products with novel properties, introduced through structural or chemical modifications (e.g.