A new liquid intravenous immunoglobulin with three dedicated virus reduction steps: virus and prion reduction capacity

Background and Objectives A new 10% liquid human intravenous immunoglobulin (US trade name: Gammagard Liquid; European trade name: KIOVIG) manufactured by a process with three dedicated pathogen inactivation/removal steps (solvent/detergent treatment, 35‐nm nanofiltration and low pH/elevated temperature incubation) was developed. The ability of the manufacturing process to inactivate/remove viruses and prions was investigated. Materials and Methods Virus and prion removal capacities were assessed with down‐scale spiking experiments, validated for equivalence to the large‐scale process. Results Lipid‐enveloped viruses were completely inactivated/removed by each of the three dedicated virus clearance steps, and for human immunodeficiency virus 1 (HIV‐1) and pseudorabies virus (PRV), also by the upstream cold ethanol fractionation step. Relevant non‐enveloped viruses [i.e. hepatitis A virus (HAV) and parvovirus B19 (B19V)] were effectively removed by nanofiltration and the cold ethanol fractionation step, and partial inactivation of non‐enveloped viruses was achieved by low pH incubation. Overall log reduction factors were > 20·0 for HIV‐1, > 18·1 for bovine viral diarrhoea virus, > 16·3 for West Nile virus, > 10·0 for influenza A virus subtype H5N1, > 21·8 for PRV, 12·0 for HAV, > 12·1 for encephalomyocarditis virus, 10·6 for B19V and 10·3 for mice minute virus. Prions (Western blot assay) were completely removed (≥ 3·2 mean log reduction) by a step of the cold ethanol fractionation process. Conclusions Introducing three dedicated virus‐clearance steps in the manufacturing process of immunoglobulins from human plasma provides high margins of safety.