This was undoubtedly true initially when many laboratories were using the test tube tilt method in the water bath to measure FVIII:C, but now with the advent of full automation selleck chemical the

same may not apply. Despite these labelling differences, initially this was not a problem because plasma-derived and the first-generation recombinant FVIII concentrates were full length molecules and gave equivalent results. The introduction of the B-domain-deleted product sold as ReFacto AF® in Europe and Xyntha® in the USA caused a problem for both manufacturers and clinical laboratories because the one-stage clotting assay gave results that were 20% lower than the chromogenic. Because of the regulatory preference in the USA the product is labelled with the one-stage clotting assay and in Europe with the chromogenic assay that resulted in the unusual current situation where 1 unit of Xyntha® is equal to 1.38 units of ReFacto AF, even though the two products are the same and come out of the same factory [8]. Measurement by clinical laboratories has continued

using the one-stage assay. Some European laboratories use a product-specific standard provided by the manufacturer that corrects the discrepancy making the one-stage results equivalent to the chromogenic assay. Product-specific standards are, however, not used in the USA possibly because the higher protein content of Xyntha does not result in clinical problems. Recently, a new recombinant Selleck ICG-001 BDD product, NovoEight® (turoctocog alfa) has been licensed click here in the USA and Europe by NovoNordisk. Despite the fact that this is also a BDD product, one chromogenic and a single APTT reagent one-stage clotting assay yielded equivalent results so a product-specific standard may not be required [9]. It is not clear why the two licensed BDD behave differently in the one-stage clotting assay but it is possible that it is due to the different degrees

of B-domain deletion of the two products with Xyntha/Refacto AF having 8 B-domain amino acids whereas NovoEight® has 22 B-domain aminoacids [10]. This is an important issue because most of the new recombinant FVIII concentrates are BDD products with different lengths of residual B-domain segments retained. A major change is about to take place in the field of haemophilia with the introduction of the long-acting concentrates. At least five different products are in development and all but one are BDD products. The concentrates from Bayer, Biogen Idec, CSL Behring and NovoNordisk are BDD while the Baxter product is full-length FVIII. Two important issues are how should these products be potency labelled and how should they be assayed by clinical laboratories. International guidelines on potency labelling of factor VIII and IX concentrates have been published [11]. To understand this issue better, in November 2013. the EMA organized a workshop between manufacturers, clinicians, patient groups and regulators. A full report will be published by the EMA in due course.