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BioDrugs
Published in: BioDrugs 3/2017

Open Access 01-06-2017 | Original Research Article

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

Authors: Caroline Goussen, Steve Simoneau, Soline Bérend, Christine Jehan-Kimmel, Anne Bellon, Céline Ducloux, Bruno You, Philippe Paolantonacci, Monique Ollivier, Ludovic Burlot, Sami Chtourou, Benoît Flan

Published in: BioDrugs | Issue 3/2017

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Abstract

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 log10 for human immunodeficiency virus type 1 (HIV-1), ≥16.9 log10 for bovine viral diarrhoea virus (BVDV)/Sindbis virus, ≥15.7 log10 for pseudorabies virus (PRV), ≥12.8 log10 for encephalomyocarditis virus (EMCV) and 11.0 log10 for porcine parvovirus (PPV). The process also exhibited a high removal capacity for the TSE agent with an overall RF of ≥12.9 log10 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 log10 for the smallest and most resistant non-enveloped virus, PPV, and more than 12 log10 for the TSE agent.
Literature
1.
Tellier Z. Intravenous immunogloblins: myth and reality. Isr Med Assoc J. 2005;7(12):762–7.PubMed
2.
Hartung HP, Mouthon L, Ahmed R, et al. Clinical applications of intravenous immunoglobulins (IVIg)–beyond immunodeficiencies and neurology. Clin Exp Immunol. 2009;158(Suppl 1):23–33.CrossRefPubMedPubMedCentral
3.
Sriaroon P, Ballow M. Immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am. 2015;35(4):713–30.CrossRefPubMed
4.
Lunemann JD, Quast I, Dalakas MC. Efficacy of intravenous immunoglobulin in neurological diseases. Neurotherapeutics. 2016;13(1):34–46.CrossRefPubMed
5.
EMA. Note for guidance on plasma-derived medicinal products. EMA/CPMP/BWP/706271/2010. London: EMA;.
6.
EMA. CHMP position statement on Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products. EMA/CHMP/BWP/303353/2010. London: EMA; 2011.
7.
EMA. Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses. CPMP/BWP/268/95 (revised). London: EMA; 1996.
8.
EMA. Guideline on the investigation of manufacturing processes for plasma-derived medicinal products with regard to vCJD risk. CPMP/BWP/CPMP/5136/03. London: EMA; 2004.
9.
Foster PR, Welch AG, McLean C, et al. Studies on the removal of abnormal prion protein by processes used in the manufacture of human plasma products. Vox Sang. 2000;78(2):86–95.CrossRefPubMed
10.
Foster PR, Welch AG, McLean C, et al. Studies on the removal of abnormal prion protein by processes used in the manufacture of human plasma products. Vox Sang. 2000;78(2):86–95.CrossRefPubMed
11.
Knipe DM, Howley PM, editors. Fields Virology. 5th ed. Lippincott Williams & Wilkins; 2006.
12.
13.
Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg. 1938;27:493–7.
14.
Flan B, Arrabal S. Manufacture of plasma-derived products in France and measures to prevent the risk of vCJD transmission: precautionary measures and efficacy of manufacturing processes in prion removal. Transfus Clin Biol. 2007;14(1):51–62.CrossRefPubMed
15.
Korneyeva M, Hotta J, Lebing W, et al. Enveloped virus inactivation by caprylate: a robust alternative to solvent-detergent treatment in plasma derived intermediates. Biologicals. 2002;30(2):153–62.CrossRefPubMed
16.
Lundblad JL, Seng RL. Inactivation of lipid-enveloped viruses in proteins by caprylate. Vox Sang. 1991;60(2):75–81.CrossRefPubMed
17.
Thyer J, Unal A, Thomas P, et al. Prion-removal capacity of chromatographic and ethanol precipitation steps used in the production of albumin and immunoglobulins. Vox Sang. 2006;91(4):292–300.CrossRefPubMed
18.
Horowitz B, Prince AM, Horowitz MS, et al. Viral safety of solvent-detergent treated blood products. Dev Biol Stand. 1993;81:147–61.PubMed
19.
Dichtelmuller HO, Biesert L, Fabbrizzi F, et al. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion. 2009;49(9):1931–43.CrossRefPubMed
20.
21.
Burnouf T, Radosevich M, Goubran HA, et al. Place of nanofiltration for assuring viral safety of biologicals. Curr Nanosci. 2005;1:189–201.CrossRef
22.
Johnston A, Uren E, Johnstone D, et al. Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin. Parametric and validation studies. Biologicals. 2003;31(3):213–21.CrossRefPubMed
23.
Trejo SR, Hotta JA, Lebing W, et al. Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process. Vox Sang. 2003;84(3):176–87.CrossRefPubMed
24.
Burnouf T. Chromatographic removal of viruses from plasma derivatives. Dev Biol Stand. 1993;81:199–209.PubMed
25.
Borovec S, Broumis C, Adcock W, et al. Inactivation kinetics of model and relevant blood-borne viruses by treatment with sodium hydroxide and heat. Biologicals. 1998;26(3):237–44.CrossRefPubMed
26.
Boschetti N, Wyss K, Mischler A, et al. Stability of minute virus of mice against temperature and sodium hydroxide. Biologicals. 2003;31(3):181–5.CrossRefPubMed
27.
Bellon A, Comoy E, Simoneau S, et al. Decontamination of prions in a plasma product manufacturing environment. Transfusion. 2014;54(4):1028–36.CrossRefPubMed
28.
Cai K, Groner A, Dichtelmuller HO, et al. Prion removal capacity of plasma protein manufacturing processes: a data collection from PPTA member companies. Transfusion. 2013;53(9):1894–905.CrossRefPubMed
29.
Foster PR, Griffin BD, Bienek C, et al. Distribution of a bovine spongiform encephalopathy-derived agent over ion-exchange chromatography used in the preparation of concentrates of fibrinogen and factor VIII. Vox Sang. 2004;86(2):92–9.CrossRefPubMed
30.
Porte P, Aubin JT, Kimmel-Jehan C, et al. Efficient prion removal by 15 nm nanofiltration after solvent-detergent treatment and ion-exchange chromatography in the manufacture of a nanofiltered factor VIII. Hemophilia 2006;12(Suppl. 2):5.
31.
Tateishi J, Kitamoto T, Mohri S, et al. Scrapie removal using Planova virus removal filters. Biologicals. 2001;29(1):17–25.CrossRefPubMed
32.
Yunoki M, Tanaka H, Urayama T, et al. Prion removal by nanofiltration under different experimental conditions. Biologicals. 2008;36(1):27–36.CrossRefPubMed
33.
34.
Bennett P, Daraktchiev M. vCJD and transfusion of blood components: an updated risk assessment. London: Department of Health; 2013.
35.
Yang H, Gregori L, Asher DM, et al. Risk assessment for transmission of variant Creutzfeldt-Jakob disease by transfusion of red blood cells in the United States. Transfusion. 2014;54(9):2194–201.CrossRefPubMed
Metadata
Title
Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma
Authors
Caroline Goussen
Steve Simoneau
Soline Bérend
Christine Jehan-Kimmel
Anne Bellon
Céline Ducloux
Bruno You
Philippe Paolantonacci
Monique Ollivier
Ludovic Burlot
Sami Chtourou
Benoît Flan
Publication date
01-06-2017
Publisher
Springer International Publishing
Published in
BioDrugs / Issue 3/2017
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI
https://doi.org/10.1007/s40259-017-0222-9

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