Analytical Characterization of Infusion Volume Reduced Humate-P®/Haemate® P.

Commercially available von Willebrand factor (VWF)/factor VIII concentrates are therapy of choice in severe von Willebrand disease (VWD), clinically characterized by serious bleedings, as well as in some cases of hemophilia A. Humate-P®/Haemate® P is one of the few products approved for therapy and prophylaxis in both indications, VWD and hemophilia A. As it was desirable to further improve the convenience of application for the patients by reducing the application volume, an infusion volume reduced (i.v.r.) Humate-P®/Haemate® P was developed increasing the product concentration while keeping the well-known positive product characteristics. Eight i.v.r. Humate-P®/Haemate® P batches were produced and vials of each batch were reconstituted using the reduced volume of water for injection, i.e. 5 mL (250 IU F VIII), 10 mL (500 IU F VIII), for 15 mL (1.000 IU F VIII). These lots were compared analytically with 18 lots of current Humate-P®/Haemate® P. The analytical comparison demonstrated that the i.v.r. product contains twofold increased concentrations of the active ingredients VWF and F VIII (see table). As the purification and virus inactivation processes have not been changed, the quality of the active ingredients is maintained. This e.g. could be shown by a high VWF:RCo/F VIII:C ratio of about 2.4 for the volume reduced as well as the current product. Additionally, the VWF:RCo/VWF:Ag ratio and the high molecular weight (HMW) multimer structure of i.v.r. Humate-P®/Haemate® P are equivalent to current Humate-P®/Haemate® P (see table) and close to that of NHP indicating a comparably good efficacy of i.v.r. and current products. Based on the analytical investigations described here, it can be concluded that the development of i.v.r. Humate-P®/Haemate® P resulted in a product of unchanged quality of the active ingredients but very high VWF concentration. This allows the application of VWF in small volumes and, consequently, will furthermore improve the convenience of VWD and hemophilia A treatment.