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

Background and Objectives  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. Materials and Methods  Several chromatographic runs were performed on the same p...

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Bibliographic Details
Published in:Vox sanguinis 2008-11, Vol.95 (4), p.298-307
Main Authors: Mori, F., Nardini, I., Rossi, P., Nardini, C., Farina, C.
Format: Article
Language:English
Subjects:
Blood & organ donations
Blood Component Removal - methods
Blood transfusions
Chromatography, Ion Exchange - methods
Drug Industry - methods
Factor VIII - isolation & purification
FVIII/VWF complex
FVIII:C
Humans
Ion chromatography
purification of FVIII
von Willebrand Factor - isolation & purification
VWF:Ag
VWF:CBA
VWF:RCo
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Summary:Background and Objectives  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. Materials and Methods  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. Results  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. Conclusions  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.
ISSN:0042-9007
1423-0410
DOI:10.1111/j.1423-0410.2008.01096.x