PMID- 28508264
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20181113
IS  - 1179-190X (Electronic)
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 31
IP  - 3
DP  - 2017 Jun
TI  - Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin 
      Preparation from Human Plasma.
PG  - 251-261
LID - 10.1007/s40259-017-0222-9 [doi]
AB  - BACKGROUND: A highly purified 10% liquid intravenous immunoglobulin, IQYMUNE((R)), 
      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((R)) 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((R)) 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((R)), 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.
FAU - Goussen, Caroline
AU  - Goussen C
AUID- ORCID: 0000-0002-4744-670X
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Simoneau, Steve
AU  - Simoneau S
AD  - LFB BIOMEDICAMENTS, 3 avenue des Tropiques, BP 40305, 91958, Courtaboeuf Cedex, 
      France.
FAU - Berend, Soline
AU  - Berend S
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Jehan-Kimmel, Christine
AU  - Jehan-Kimmel C
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Bellon, Anne
AU  - Bellon A
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Ducloux, Celine
AU  - Ducloux C
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - You, Bruno
AU  - You B
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Paolantonacci, Philippe
AU  - Paolantonacci P
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Ollivier, Monique
AU  - Ollivier M
AD  - LFB BIOMEDICAMENTS, 3 avenue des Tropiques, BP 40305, 91958, Courtaboeuf Cedex, 
      France.
FAU - Burlot, Ludovic
AU  - Burlot L
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Chtourou, Sami
AU  - Chtourou S
AD  - LFB BIOTECHNOLOGIES, Les Ulis, France.
FAU - Flan, Benoit
AU  - Flan B
AD  - LFB BIOMEDICAMENTS, 3 avenue des Tropiques, BP 40305, 91958, Courtaboeuf Cedex, 
      France. flan@lfb.fr.
LA  - eng
PT  - Journal Article
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
RN  - 0 (Caprylates)
RN  - 0 (Hemagglutinins)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Prions)
RN  - 0 (Solvents)
RN  - OBL58JN025 (octanoic acid)
SB  - IM
MH  - Animals
MH  - Caprylates/chemistry
MH  - Chromatography, Affinity/methods
MH  - Cricetinae
MH  - Drug Contamination/prevention & control
MH  - Hemagglutinins/chemistry
MH  - Humans
MH  - Immunoglobulins, Intravenous/*chemistry/pharmacology
MH  - Plasma/*chemistry
MH  - Prion Diseases/drug therapy/virology
MH  - Prions/drug effects
MH  - Solvents/chemistry
MH  - Virus Inactivation/drug effects
MH  - Viruses/drug effects
PMC - PMC5443886
COIS- FUNDING: Financial support for the conduct of the studies and preparation of the 
      manuscript was provided by LFB. CONFLICTS OF INTEREST: The authors (CG, SS, SB, 
      AB, CD, BY, PP, MO, LB, SC and BF) declare that they are employees of LFB, a 
      pharmaceutical company that manufactures and commercialises IQYMUNE. CJ-K was 
      employed by LFB at the time the experiments were carried out and the manuscript 
      was prepared. ETHICAL APPROVAL: Viral and prion clearance studies were carried 
      out in accordance with the principles of Good Laboratory Practice (as required by 
      international regulatory guidelines) with a specialised Contract Research 
      Organisation. Applicable international, national and/or institutional guidelines 
      for the care and use of animals were followed at the place where animal studies 
      were conducted.
EDAT- 2017/05/17 06:00
MHDA- 2018/03/07 06:00
PMCR- 2017/05/15
CRDT- 2017/05/17 06:00
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2017/05/17 06:00 [entrez]
PHST- 2017/05/15 00:00 [pmc-release]
AID - 10.1007/s40259-017-0222-9 [pii]
AID - 222 [pii]
AID - 10.1007/s40259-017-0222-9 [doi]
PST - ppublish
SO  - BioDrugs. 2017 Jun;31(3):251-261. doi: 10.1007/s40259-017-0222-9.