title: Development of an intravenous immunoglobulin with improved safety and functional activity.
abstract: The development and properties of a liquid intravenous immunoglobulin (Gammaplex(®)), of high purity, stability and functional activity, is described. Virus and TSE reduction by specific steps in the process were evaluated by spiking studies using small-scale models. The removal of procoagulant activity was determined using immunochemical and functional activity assays. Neutralisation and opsonic activity were used to demonstrate the functional activity of the IgG. The final low pH formulated product was stable at room temperature and was of high purity and functional activity. Three dedicated virus inactivation steps, i.e. solvent detergent, low pH and virus filtration, were shown to be effective. When combined with the B + I ethanol precipitation step, this gave a total reduction of >21 to >24 log for the enveloped and >10 to >13 log for the non-enveloped viruses tested. Several steps in the process were shown to contribute to TSE removal using scrapie. Potential procoagulant activity including Factor XI/XIa, was reduced to very low/undetectable levels in the final product. A new high purity liquid IVIG product has been developed, of high purity and good functional activity and stability. The process includes various steps for the removal of pathogens and procoagulant activity.
authors.affiliation: Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK. Electronic address: peter.roberts@bpl.co.uk.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Roberts
authors.affiliation: Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK.
authors.forename: Tara
authors.initials: T
authors.lastname: Dolan
authors.affiliation: Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK.
authors.forename: Martyn
authors.initials: M
authors.lastname: Paddick
authors.affiliation: Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK.
authors.forename: Shirley
authors.initials: S
authors.lastname: Stagg
authors.affiliation: Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK.
authors.forename: John E
authors.initials: JE
authors.lastname: More
mesh_terms: D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D038301:Virus Inactivation
chemical_list: D016756:Immunoglobulins, Intravenous; D000431:Ethanol
keywords: Functional activity; Gammaplex(®); Intravenous immunoglobulin; Pathogen reduction; Procoagulant activity; Thromboembolic potential