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

Vox Sang. 2008 Apr;94(3):184-92. doi: 10.1111/j.1423-0410.2007.01016.x. Epub 2007 Dec 19.

Abstract

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 (> or = 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.

Publication types

  • Validation Study

MeSH terms

  • Cytopathogenic Effect, Viral
  • Detergents
  • Drug Contamination / prevention & control
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoglobulins, Intravenous / isolation & purification*
  • Micropore Filters
  • Polymerase Chain Reaction
  • Prions / isolation & purification*
  • Safety
  • Solvents
  • Temperature
  • Ultrafiltration
  • Virus Inactivation
  • Viruses / genetics
  • Viruses / isolation & purification*

Substances

  • Detergents
  • Immunoglobulins, Intravenous
  • Prions
  • Solvents