Preclinical characterization of a new liquid “immune globulin intravenous (human), 10% triple virally reduced solution” (IGIV, 10%TVR)

Abstract

Rationale In preclinical testing the efficacy, safety, pharmacokinetics, and toxicity of a new liquid 10% intravenous immunoglobulin preparation (IGIV, 10%TVR) was compared with Gammagard® S/D, a licensed lyophilized immunoglobulin for intravenous infusion. Methods Efficacy is proved in vivo by mouse protection testing and in vitro by opsonization and affinity chromatography using protein A Sepharose. The blood-pressure-lowering effect in spontaneously hypertensive rats and the bronchospastic effect in guinea pigs are used as indicators of the anaphylactoid potential. Pharmacokinetics in rats is evaluated by the variables “in vivo recovery” and “half-life” after a single intravenous dose of 1000 mg/kg. Thrombogenicity is assessed in a rabbit model and the influence of the products on vital functions like cardiovascular, respiratory and blood coagulation variables is tested in dogs. Acute toxicity studies are carried out in mice and rats. Results The mouse protection test showed that the protective activity against systemic bacterial infections of IGIV, 10%TVR is at least as good as the reference Gammagard S/D. This result is supported by the broad spectrum of antibodies in high titers against bacteria and viruses and the high functional integrity of the IgG molecule (≥90% functional intact IgG) in IGIV, 10%TVR. In safety and thrombogenicity studies, no adverse effects of IGIV, 10%TVR were observed. Pharmacokinetic studies showed no statistically significant differences between the two products. In the acute toxicity animal studies, IGIV, 10%TVR was better tolerated than the reference Gammagard S/D. Conclusions Liquid IGIV, 10%TVR combines excellent qualities of efficacy, safety and tolerability.