NEW METHOD FOR THE PURIFICATION OF FACTOR VIII VIII/FvW CONCENTRATE STUDY PUBLISHED ON
30/10/2008

The study Progress in large-scale purification of Factor VIII/von Willebrand factor concentrates using ion-exchange chromatographyhas been published on “Vox Sanguinis” (2008) 95, 298–307,

Entirely conducted by Kedrion’s researchers, the study presents the results of the development of a new purification method for a Factor VIII/von Willebrand Factor concentrate. A process scale-up is now being investigated for industrial feasibility.

The authors of the study are Filippo Mori, Ilaria Nardini, Paola Rossi, Claudio Farina (basic research manager) and Claudia Nardini (industrial research and development manager).

The trial described in the article helped develop a new purification process for Factor VIII/von Willebrand factor with a high yield and purity. Once the chromatographic parameters are optimised, the selected resin (Fractogel EMD TMAE) can process twice as much product as the ordinary production process, which will also save on processing time. The new purification process can be used to adjust the vWF content in the end product, so the result will be one or more very pure and stable drugs specifically designed to treat Haemophilia A or Von Willebrand disease



Progress in large-scale purification of Factor VIII/von Willebrand factor concentrates using ion-exchange chromatography

F. Mori, I. Nardini, P. Rossi, C. Nardini & C. Farina

ABSTRACT

We investigated and optimized the parameters of a chromatographic process suitable for industrial scale to obtain a highly purified factor VIII (FVIII)/von Willebrand factor (VWF) concentrate. Several chromatographic runs were performed on the same production intermediate using different anion-exchange supports. The best matrix was selected and the final product was characterized. Once the chromatographic medium was chosen, the other parameters were evaluated to obtain the highest purified product and to modulate the VWF content in the FVIII/VWF complex. Fractogel EMD TMAE was the best support among those tested. It was the only one maintaining good results either with standard or double loading and flow rate conditions with respect to a typical industrial process. The chromatographic recovery of FVIII co-purified with VWF was at least 86% with a specific activity not lower than 140 IU/mg. The FVIII/VWF complex obtained is highly pure and, with the exception of immunoglobulin M (IgM), all investigated contaminant proteins are under the detection limit. Different concentrates characterized by variable FVIII/VWF ratios were purified by varying the chromatographic conditions. Several highly purified products, suitable for haemophilia A and von Willebrand disease management, can be obtained, through the same chromatographic process, on an industrial scale.

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