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. 2017 Apr;31(2):125-134.
doi: 10.1007/s40259-017-0212-y.

Pathogen Safety of a New Intravenous Immune Globulin 10% Liquid

Kai Uwe Radomski  1 , Georg Lattner  2 , Torben Schmidt  3 , Jürgen Römisch  2
Affiliations

Pathogen Safety of a New Intravenous Immune Globulin 10% Liquid

Kai Uwe Radomski et al. BioDrugs. 2017 Apr.

Abstract

Background: The manufacturing process of a new intravenous immune globulin (IVIG) 10% liquid product incorporates two dedicated pathogen safety steps: solvent/detergent (S/D) treatment and nanofiltration (20 nm). Ion-exchange chromatography (IEC) during protein purification also contributes to pathogen safety. The ability of these three process steps to inactivate/remove viruses and prions was evaluated.

Objectives: The objective of this study was to evaluate the virus and prion safety of the new IVIG 10% liquid.

Methods: Bovine viral diarrhea virus (BVDV), human immunodeficiency virus type 1 (HIV-1), mouse encephalomyelitis virus (MEV), porcine parvovirus (PPV), and pseudorabies virus (PRV) were used as models for common human viruses. The hamster-adapted scrapie strain 263K (HAS 263K) was used for transmissible spongiform encephalopathies. Virus clearance capacity and robustness of virus reduction were determined for the three steps. Abnormal prion protein (PrPSc) removal and infectivity of the samples was determined.

Results: S/D treatment and nanofiltration inactivated/removed enveloped viruses to below detection limits. IEC supplements viral safety and nanofiltration was highly effective in removing non-enveloped viruses and HAS 263K. Overall virus reduction factors were: ≥9.4 log10 (HIV-1), ≥13.2 log10 (PRV), ≥8.2 log10 (BVDV), ≥11.7 log10 (MEV), ≥11.6 log10 (PPV), and ≥10.4 log10 (HAS 263K).

Conclusion: Two dedicated and one supplementing steps in the manufacturing process of the new IVIG 10% liquid provide a high margin of pathogen safety.

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Conflict of interest statement

Conflict of Interest

KUR, TS, GL, and JR are employees of Octapharma.

Funding

Financial support for the conduct of the research and preparation of the manuscript was provided by Octapharma.

Ethical Considerations

Pathogen safety studies were conducted in accordance with the principles of Good Laboratory Practice (Octapharma Biopharmaceuticals GmbH, Frankfurt am Main, Germany; ViruSure GmbH, Vienna, Austria), as required by the Committee for Proprietary Medicinal Products of the European Medicines Agency [14]. Animal infectivity studies were undertaken at a specialized animal facility (ViruSure). All animal procedures performed at ViruSure were approved by the Austrian Federal Ministry of Science and Research (Authorization No. BMWF-68.205/0056-II/10b/2010) and conducted according to the Austrian animal rights act (BGBL. I Nr. 169/1999) and legislative decree (BGBL II Nr.198/2000).

Figures

Fig. 1
Fig. 1
Change in viral load after the solvent/detergent treatment step, under (a) standard conditions and (b) robustness conditions (see Sect. 2.5.1). BVDV bovine viral diarrhea virus, HIV human immunodeficiency virus, LOD limit of detection, PRV porcine pseudorabies virus, TCID 50 50% tissue culture infectious dose
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