However, to maintain a harmonized therapeutic approach at the global level, it is crucial that licensing authorities and manufacturers agree on the route towards the potency labelling of individual products. Once the unitage for a product has been established, this could be transferred to the manufacturer’s product reference preparation, which would restore a

“like vs like” situation and resolve methods discrepancies as demonstrated previously [29,31]. Where it is not possible to obtain valid estimates in IU relative to the WHO IS, it may be Selleck Opaganib necessary to label in arbitrary “product-specific units”, based on in vitro biological activity relating to product references. This strategy was previously applied to plasma-derived porcine factor VIII, which was labelled in “porcine units” [32]. The assay of FVIII concentrates against plasma standards has been a long-standing problem because of wide variability among laboratories and assay methods. For this reason, two separate WHO standards for plasma and concentrates were developed. However, although such comparisons are avoided in routine assays, they are relevant to manufacturers of plasma-derived concentrates,

and especially to EPZ015666 concentration clinicians measuring in vivo recovery. In the latter situation, patients’ postinfusion samples, which essentially consist of concentrates ‘diluted’ in the patient’s haemophilic plasma, are assayed against a plasma standard. Carnitine palmitoyltransferase II In 1978 [9], it was found that when concentrates were assayed against plasma, the potencies were higher by the two-stage method than by one-stage assays – the average discrepancy from a number of collaborative studies at this time was 20%. Since then, the same trend has been found in almost every collaborative study, although the size of the discrepancy varies from study

to study, and possibly with different types of concentrates. In recent years, the chromogenic method has largely replaced the two-stage clotting method for assay of concentrates, and not surprisingly it also gives higher results than the one-stage method, being based on the same principles as the two-stage assay. A possible cause of this discrepancy may be the extensive processing applied to both plasma-derived and recombinant concentrates, which could lead to differences in their rates of activation and inactivation in the two method types from the FVIII in normal plasma; there is some evidence for this [33]. There is also evidence that the discrepancy is greater for recombinant concentrates than for plasma-derived products. In the collaborative study to calibrate the 5th IS FVIII concentrate, the ratio of chromogenic to one-stage potencies for a recombinant concentrate vs. the WHO plasma standard was 1.48, and in the sixth IS study [34] it was 1.26. These figures help to explain the large discrepancies between chromogenic and one-stage potencies found in patients’ samples after infusion of recombinant concentrates [31].