title: Viral safety characteristics of Flebogamma DIF, a new pasteurized, solvent-detergent treated and Planova 20 nm nanofiltered intravenous immunoglobulin.
abstract: A new human liquid intravenous immunoglobulin product, Flebogamma DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log(10) TCID(50)) or Plaque Forming Units assay (log(10) PFU). Validation studies demonstrated that each specific step cleared more than 4 log(10) for all viruses assayed. An overall viral clearance between > or =13.33 log(10) and > or =25.21 log(10), was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma DIF has a very high viral safety profile.
authors.affiliation: Research and Development Area, Instituto Grifols S.A, Polígono Levante, C/Can Guasch 2, 08150 Parets del Vallés, Barcelona, Spain. santiago.caballero@grifols.com
authors.forename: Santiago
authors.initials: S
authors.lastname: Caballero
authors.forename: Sandra
authors.initials: S
authors.lastname: Nieto
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gajardo
authors.forename: Juan I
authors.initials: JI
authors.lastname: Jorquera
mesh_terms: D005591:Chemical Fractionation; D002852:Chromatography, Ion Exchange; D003902:Detergents / Q000737:chemistry; D004340:Drug Contamination / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry / Q000302:isolation & purification* / Q000592:standards*; D010949:Plasma / Q000737:chemistry / Q000821:virology; D011092:Polyethylene Glycols / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013242:Sterilization / Q000379:methods; D014462:Ultrafiltration / Q000295:instrumentation / Q000379:methods; D010948:Viral Plaque Assay; D038301:Virus Inactivation
chemical_list: D003902:Detergents; D016756:Immunoglobulins, Intravenous; D012997:Solvents; D011092:Polyethylene Glycols