Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma

BACKGROUND: A highly purified 10% liquid intravenous immunoglobulin, IQYMUNE(®), has been developed using an innovative manufacturing process including an affinity chromatography step for the removal of anti-A and anti-B hemagglutinins. OBJECTIVES: The pathogen (viruses and prions) clearance efficacy of the manufacturing process and its robustness for critical steps were investigated. METHODS: The manufacturing process of IQYMUNE(®) includes two dedicated complementary virus reduction steps: solvent/detergent (S/D) treatment and 20 nm nanofiltration as well as two contributing steps, namely caprylic acid fractionation and anion-exchange chromatography. The clearance capacity and robustness of these steps were evaluated with a wide range of viruses (enveloped and non-enveloped) and with a model of human transmissible spongiform encephalopathies (TSEs). RESULTS: The IQYMUNE(®) manufacturing process demonstrated a high and robust virus removal capacity with global reduction factors (RFs) of relevant and model viruses: ≥14.8 log(10) for human immunodeficiency virus type 1 (HIV-1), ≥16.9 log(10) for bovine viral diarrhoea virus (BVDV)/Sindbis virus, ≥15.7 log(10) for pseudorabies virus (PRV), ≥12.8 log(10) for encephalomyocarditis virus (EMCV) and 11.0 log(10) for porcine parvovirus (PPV). The process also exhibited a high removal capacity for the TSE agent with an overall RF of ≥12.9 log(10) due to the complementary actions of the caprylic acid fractionation, anion-exchange chromatography and nanofiltration steps. CONCLUSION: Data from virus and prion clearance studies fully support the high safety profile of IQYMUNE(®), with a minimal reduction of 11 log(10) for the smallest and most resistant non-enveloped virus, PPV, and more than 12 log(10) for the TSE agent.