Manufacturing process of anti-thrombin III concentrate: viral safety validation studies and effect of column re-use on viral clearance. |
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Authors: | Antonietta Morrica Claudia Nardini Anna Falbo Andrew C Bailey E Bucci |
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Institution: | Kedrion S.p.A. (formerly Farma Biagini S.p.A.), V. Provinciale 1, 55027, Gallicano (Lucca), Bolognana, Italy. |
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Abstract: | A manufacturing process for the production of Anti-thrombin IIII concentrate is described, which is based primarily on Heparin Sepharose affinity chromatography. The process includes two sequential viral inactivation/removal procedures, applied to the fraction eluted from the column, the first by heating in aqueous solution at 60 degrees C for 10 h and the second by nanofiltration. Using viral validation on a scaled-down process both treatments proved to be effective steps; able to inactivate or remove more than 4 logs of virus, and their combined effect (>8 logs) assured the safety of the final product. Viral validation studies of the Heparin Sepharose chromatographic step demonstrated a consistency of the affinity of the resin for viruses over repeated use (16 runs), thus providing evidence of absence of cross-contamination from one batch to the next. It was concluded that the process of ATIII manufacturing provides a high level of confidence that the product will not transmit viruses. |
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