title: Improvement of virus safety of an antihemophilc factor IX by virus filtration process.
abstract: Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Nonenveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were >or=6.12 for HAV, >or=4.28 for PPV, >or=5.33 for EMCV, >or=5.51 for HIV, >or=5.17 for BVDV, and >or=5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.
authors.affiliation: Department of Biological Sciences, College of Life Science and Nanotechnology, Hannam University, Daejon, Korea. inskim@hannam.ac.kr
authors.forename: In Seop
authors.initials: IS
authors.lastname: Kim
authors.forename: Yong Woon
authors.initials: YW
authors.lastname: Choi
authors.forename: Yong
authors.initials: Y
authors.lastname: Kang
authors.forename: Hark Mo
authors.initials: HM
authors.lastname: Sung
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Sohn
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D003029:Coagulants / Q000302:isolation & purification / Q000494:pharmacology; D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry / Q000379:methods; D005164:Factor IX / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010949:Plasma / Q000737:chemistry*; D013696:Temperature; D014462:Ultrafiltration / Q000379:methods*; D038301:Virus Inactivation; D014780:Viruses / Q000302:isolation & purification
chemical_list: D003029:Coagulants; D005164:Factor IX