title: Manufacturing process of anti-thrombin III concentrate: viral safety validation studies and effect of column re-use on viral clearance.
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.
authors.affiliation: Kedrion S.p.A. (formerly Farma Biagini S.p.A.), V. Provinciale 1, 55027, Gallicano (Lucca), Bolognana, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Morrica
authors.forename: Claudia
authors.initials: C
authors.lastname: Nardini
authors.forename: Anna
authors.initials: A
authors.lastname: Falbo
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Bailey
authors.forename: E
authors.initials: E
authors.lastname: Bucci
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000302:isolation & purification*; D002417:Cattle; D005591:Chemical Fractionation; D002846:Chromatography, Affinity; D003257:Consumer Product Safety; D001908:Diarrhea Viruses, Bovine Viral / Q000302:isolation & purification; D004340:Drug Contamination / Q000517:prevention & control*; D015497:HIV-1 / Q000302:isolation & purification; D011558:Herpesvirus 1, Suid / Q000302:isolation & purification; D006358:Hot Temperature; D006801:Humans; D012087:Reoviridae / Q000302:isolation & purification; D013242:Sterilization; D013552:Swine; D014462:Ultrafiltration; D014780:Viruses / Q000302:isolation & purification*
chemical_list: D000990:Antithrombin III