Biochemical Comparison of VWF/FVIII Concentrates - Are There Differences in Product Characteristics and Purity?.

Introduction: Product characteristics and purity are important in assessing the safety and efficacy of VWF/FVIII products. Purity has been defined as the specific activity of the active ingredients in relation to the total protein in the products. This is important because it indicates the content of co-purified plasma proteins in the product. An extensive biochemical comparison of several VWF/FVIII concentrates licensed for the treatment of Haemophilia A and/or von Willebrand disease (VWD), including the novel new generation VWF/FVIII concentrate (Wilate), was performed to compare their properties.

Methods: Different batches of a number of commercially available VWF and VWF/FVIII products were analysed using state-of-the-art VWF and FVIII assays including VWF multimer analysis with examination of the multimeric triplet structure. The total protein as well as any accompanying plasma proteins, which may co-harvested in the final concentrate, were also quantified.

Results: All concentrates generally contained the specified VWF and FVIII amounts and activities. The VWF and FVIII specific activities and overall purity was highest for Wilate®, while all other concentrates contained considerable amounts of albumin used as a stabilizer as well as other residual plasma proteins that where found in varied concentration specific for the concentrate. The VWF:RCo/FVIII:C ratios varied greatly. The new generation product (Wilate®) was the only product tested that has high purity and showed a physiological 1:1 ratio. As compared to some of the other products, Wilate’s, native multimeric triplet structure was preserved.

Conclusion: There was a great variation in properties and purity of the concentrates tested. The new generation VWF/FVIII concentrate (Wilate®), showed a high purity and physiological VWF/FVIII ratio that should reduce the load of non-essential proteins given to the patient during treatment. Even though there are some differences in the content of the highest VWF multimers in this concentrate, the role of this in the in vivo physiological process of clot formation has not been established. The altered triplet structure seen in some of the older generation products may be the result of proteolysis in the manufacturing process. The clinical consequence of this has also not been established. The physiologic ratio of VWF and FVIII as well as their optimal PK profile, may ease the difficulties of dosing and monitoring in these patients.