title: Flebogamma 5% DIF development: rationale for a new option in intravenous immunoglobulin therapy.
abstract: Flebogamma 5% dual inactivation and filtration (DIF), a new 5% liquid intravenous immunoglobulin with a stability of 2 years when stored at temperatures between 2 and 30 degrees C, has been developed. This new product is the result of the accumulated experience provided by Flebogamma, with more than 30 million grams administered since 1992 in Europe and the United States, and the implementation of the latest technology to improve Flebogamma even more by increasing its viral safety margin further. In addition to the specific inactivation stage for Flebogamma 5% (pasteurization), the new process includes a solvent-detergent treatment and nanofiltration through a Planova filter down to 20 nm. The preparation presents a mean purity of 99.6 +/- 0.2% with a correct chromatographic profile. Percentage values of immunoglobulin (Ig)G subclasses are equivalent to the physiological values of normal serum. The content in IgA as well as other possible impurities is very low, and the product presents a mean result of 109 +/- 5% in the Fc fragment functionality assay, demonstrating the integrity of the IgG molecule. The functionality is also reflected in neutralization tests carried out against poliomyelitis, diphtheria, measles and vaccinia which, apart from the antibody titres determined by enzyme-linked immunosorbent assay, guarantees that antibodies are capable of reacting against these pathogens. Regarding safety, the combination of multiple methods with capacity to inactivate or remove biological agents which include chemical inactivation, heat inactivation, nanofiltration and precipitations, with very different mechanisms of action, provides Flebogamma 5% DIF very wide margins of safety regarding to potential pathogens.
authors.affiliation: Research and Development Area, Instituto Grifols S.A., Barcelona, Spain. juan.jorquera@grifols.com
authors.forename: J I
authors.initials: JI
authors.lastname: Jorquera
mesh_terms: D004340:Drug Contamination / Q000517:prevention & control; D055808:Drug Discovery / Q000379:methods; D004355:Drug Stability; D006801:Humans; D007122:Immunoelectrophoresis / Q000379:methods; D007074:Immunoglobulin G / Q000032:analysis; D016756:Immunoglobulins, Intravenous / Q000737:chemistry / Q000276:immunology / Q000592:standards*; D008970:Molecular Weight; D036103:Nanotechnology / Q000379:methods; D017751:Safety Management / Q000379:methods; D014462:Ultrafiltration / Q000379:methods; D038301:Virus Inactivation; D014780:Viruses / Q000302:isolation & purification
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous