title: Investigations of prion and virus safety of a new liquid IVIG product.
abstract: A highly purified, liquid, 10% immunoglobulin product stabilized with proline, referred to as IgPro10 has recently been developed. IgG was purified from human plasma by cold ethanol fractionation, octanoic acid precipitation and anion-exchange chromatography. The manufacturing process includes two distinctly different partitioning steps and virus filtration, which were also assessed for the removal of prions. Prion removal studies used different spike preparations (brain homogenate, microsomes, purified PrP(sc)) and three different detection methods (bioassay, Western blot, conformation-dependent immunoassay). All of the investigated production steps were shown to reduce significantly all different spike preparations, resulting in an overall reduction of >10log(10). Moreover, the biochemical assays proved equally effective to the bioassay for the demonstration of prion elimination. Four of the manufacturing steps cover three different mechanisms of virus clearance. These are: i) virus inactivation; ii) virus filtration; and iii) partitioning. These mechanisms were assessed for their virus reduction capacity. Virus validation studies demonstrated overall reduction factors of >18log(10) for enveloped and >7log(10) for non-enveloped model viruses. In conclusion, the IgPro10 manufacturing process has a very high reduction potential for prions and for a wide variety of viruses resulting in a state-of-the-art product concerning safety towards known and emerging pathogens.
authors.affiliation: CSL Behring AG, Wankdorfstrasse 10, CH-3000 Bern 22, Switzerland. martin.stucki@cslbehring.com
authors.forename: M
authors.initials: M
authors.lastname: Stucki
authors.forename: N
authors.initials: N
authors.lastname: Boschetti
authors.forename: W
authors.initials: W
authors.lastname: Schäfer
authors.forename: T
authors.initials: T
authors.lastname: Hostettler
authors.forename: F
authors.initials: F
authors.lastname: Käsermann
authors.forename: T
authors.initials: T
authors.lastname: Nowak
authors.forename: A
authors.initials: A
authors.lastname: Gröner
authors.forename: C
authors.initials: C
authors.lastname: Kempf
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D005591:Chemical Fractionation; D006224:Cricetinae; D003666:Decontamination / Q000379:methods* / Q000592:standards; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000737:chemistry* / Q000592:standards; D011328:Prions / Q000302:isolation & purification*; D038301:Virus Inactivation; D014780:Viruses / Q000302:isolation & purification*
chemical_list: D016756:Immunoglobulins, Intravenous; D011328:Prions