Description:
<jats:title>Abstract</jats:title>
<jats:p>Purpose: This study summarizes the characteristics and virus safety profile of Wilate®, a new human plasma-derived, high purity, double virus inactivated VWF/FVIII concentrate. The manufacturing process comprises two chromatographic steps, ensuring high purity and preserving the integrity and functionality of the VWF/FVIII complex. The optimised solvent/detergent treatment (S/D) and terminal dry-heat treatment (PermaHeat) of the lyophilised product provide two effective and robust virus inactivation steps for enveloped (EV) and one step for non-enveloped viruses (NEV).</jats:p>
<jats:p>Methods: Functional and structural properties of the VWF/FVIII concentrate were studied utilising state-of-the-art assays. The reduction factors for a panel of model viruses were determined in down-scale experiments valid for the respective manufacturing steps.</jats:p>
<jats:p>Summary of results: The integrity of the VWF/FVIII concentrate was confirmed by all tests. The ratio between VWF:RCo and FVIII:C was close to that in plasma of blood donors. The VWF multimeric profile demonstrated >10 bands in all batches and the triplet structure was very well preserved. A high specific activity, on average 122 IU FVIII:C/mg total protein, was measured in 15 batches recently produced. SE–HPLC revealed a one-peak-product, representing the VWF/FVIII-complex. All viruses tested were rapidly inactivated by at least 4 log10. The PermaHeat treatment of the lyophilised product at +100°C for 2 hours, at a specified residual moisture of 0.7–1.6%, was efficient for the inactivation of both EV and NEV.</jats:p>
<jats:p>Conclusion: Wilate® is a high purity, double virus inactivated concentrate containing functional VWF and FVIII in a ratio close to plasma of healthy subjects. The product has an excellent viral safety profile. The safe and effective treatment of patients with von Willebrand disease and haemophilia A was demonstrated in multiple clinical trials.</jats:p>