BACKGROUND AND OBJECTIVES: Patients suffering from von Willebrand disease who are not responsive to desmopressin require substitutive treatment. This study was part of the development of a second-generation plasma-derived von Willebrand factor (VWF) concentrate, the manufacturing process of which includes two complementary viral-inactivation/elimination steps that are effective against non-enveloped viruses. MATERIALS AND METHODS: VWF was purified from solvent/detergent-treated cryoprecipitate through a combination of anion-exchange and affinity chromatography. The VWF preparation was diluted and filtered through filters with pore size of 35 nm. After concentration and formulation, the product was freeze-dried and further heated at 80 degrees C for 72 h. Tests were performed to evaluate the effects of nanofiltration and dry heating on VWF multimeric structure and function. RESULTS: Nanofiltration and dry heating of the formulated product increased viral safety but did not modify VWF multimeric structure. Furthermore, these steps did not alter the ability of VWF to bind to platelet glycoprotein Ib, collagen and Factor VIII. CONCLUSIONS: We have perfected a large-scale manufacturing process to produce a human plasma-derived VWF concentrate that boasts high specific activity and is very safe for the treatment of patients with von Willebrand disease.
BACKGROUND AND OBJECTIVES:Patients suffering from von Willebrand disease who are not responsive to desmopressin require substitutive treatment. This study was part of the development of a second-generation plasma-derived von Willebrand factor (VWF) concentrate, the manufacturing process of which includes two complementary viral-inactivation/elimination steps that are effective against non-enveloped viruses. MATERIALS AND METHODS:VWF was purified from solvent/detergent-treated cryoprecipitate through a combination of anion-exchange and affinity chromatography. The VWF preparation was diluted and filtered through filters with pore size of 35 nm. After concentration and formulation, the product was freeze-dried and further heated at 80 degrees C for 72 h. Tests were performed to evaluate the effects of nanofiltration and dry heating on VWF multimeric structure and function. RESULTS: Nanofiltration and dry heating of the formulated product increased viral safety but did not modify VWF multimeric structure. Furthermore, these steps did not alter the ability of VWF to bind to platelet glycoprotein Ib, collagen and Factor VIII. CONCLUSIONS: We have perfected a large-scale manufacturing process to produce a human plasma-derived VWF concentrate that boasts high specific activity and is very safe for the treatment of patients with von Willebrand disease.
Authors: Nathan J Roth; Herbert O Dichtelmüller; Fabrizio Fabbrizzi; Eckhard Flechsig; Albrecht Gröner; Mary Gustafson; Juan I Jorquera; Thomas R Kreil; Dominika Misztela; Elisa Moretti; Mila Moscardini; Gerhard Poelsler; John More; Peter Roberts; Andreas Wieser; Rodrigo Gajardo Journal: Transfusion Date: 2020-08-19 Impact factor: 3.157