title: Viral safety of C1-inhibitor NF.
abstract: We studied the efficacy of virus reduction by three process steps (polyethylene glycol 4000 (PEG) precipitation, pasteurization, and 15nm virus filtration) in the manufacturing of C1-inhibitor NF. The potential prion removing capacity in this process was estimated based on data from the literature. Virus studies were performed using hepatitis A virus (HAV) and human immunodeficiency virus (HIV) as relevant viruses and bovine viral diarrhea virus (BVDV), canine parvovirus (CPV) and pseudorabies virus (PRV) as model viruses, respectively. In the PEG precipitation step, an average reduction in infectious titer of 4.5log(10) was obtained for all five viruses tested. Pasteurization resulted in reduction of infectious virus of >6log(10) for BVDV, HIV, and PRV; for HAV the reduction factor was limited to 2.8log(10) and for CPV it was zero. Virus filtration (15nm) reduced the infectious titer of all viruses by more than 4.5log(10). The overall virus reducing capacity was >16log(10) for the LE viruses. For the NLE viruses CPV and HAV, the overall virus reducing capacities were >8.7 and >10.5log(10), respectively. Based on literature and theoretical assumptions, the prion reducing capacity of the C1-inhibitor NF process was estimated to be >9log(10).
authors.affiliation: Sanquin Research and Landsteiner Laboratory of the Academic Medical Center of the University of Amsterdam, The Netherlands. f.terpstra@sanquin.nl
authors.forename: F G
authors.initials: FG
authors.lastname: Terpstra
authors.forename: M
authors.initials: M
authors.lastname: Kleijn
authors.forename: A H L
authors.initials: AH
authors.lastname: Koenderman
authors.forename: J
authors.initials: J
authors.lastname: Over
authors.forename: F A C
authors.initials: FA
authors.lastname: van Engelenburg
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: A B
authors.initials: AB
authors.lastname: van 't Wout
mesh_terms: D000818:Animals; D001688:Biological Products / Q000302:isolation & purification*; D002417:Cattle; D002460:Cell Line; D011232:Chemical Precipitation; D003174:Complement C1 Inactivator Proteins / Q000302:isolation & purification*; D050718:Complement C1 Inhibitor Protein; D001908:Diarrhea Viruses, Bovine Viral / Q000302:isolation & purification; D004203:Disinfection; D004285:Dogs; D004340:Drug Contamination; D005374:Filtration; D006678:HIV / Q000302:isolation & purification; D030041:Hepatitis A virus / Q000302:isolation & purification; D011558:Herpesvirus 1, Suid / Q000302:isolation & purification; D006801:Humans; D036103:Nanotechnology; D017993:Parvovirus, Canine / Q000302:isolation & purification; D011092:Polyethylene Glycols; D012449:Safety; D015843:Serpins / Q000302:isolation & purification*; D013552:Swine; D014780:Viruses / Q000302:isolation & purification*
chemical_list: D001688:Biological Products; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D015843:Serpins; D011092:Polyethylene Glycols