一种高纯度人血浆来源10%液体静脉注射免疫球蛋白制剂的生物安全性
Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma.
作者信息
Goussen Caroline, Simoneau Steve, Bérend Soline, Jehan-Kimmel Christine, Bellon Anne, Ducloux Céline, You Bruno, Paolantonacci Philippe, Ollivier Monique, Burlot Ludovic, Chtourou Sami, Flan Benoît
机构信息
LFB BIOTECHNOLOGIES, Les Ulis, France.
LFB BIOMEDICAMENTS, 3 avenue des Tropiques, BP 40305, 91958, Courtaboeuf Cedex, France.
出版信息
BioDrugs. 2017 Jun;31(3):251-261. doi: 10.1007/s40259-017-0222-9.
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 log for human immunodeficiency virus type 1 (HIV-1), ≥16.9 log for bovine viral diarrhoea virus (BVDV)/Sindbis virus, ≥15.7 log for pseudorabies virus (PRV), ≥12.8 log for encephalomyocarditis virus (EMCV) and 11.0 log for porcine parvovirus (PPV). The process also exhibited a high removal capacity for the TSE agent with an overall RF of ≥12.9 log 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 log for the smallest and most resistant non-enveloped virus, PPV, and more than 12 log for the TSE agent.
背景
已采用创新的生产工艺研发出一种高度纯化的10%液体静脉注射免疫球蛋白IQYMUNE，该工艺包括用于去除抗A和抗B血凝素的亲和色谱步骤。
目的
研究生产工艺的病原体（病毒和朊病毒）清除效果及其关键步骤的稳健性。
方法
IQYMUNE的生产工艺包括两个专门的互补病毒去除步骤：溶剂/去污剂（S/D）处理和20纳米纳滤，以及两个辅助步骤，即辛酸分级分离和阴离子交换色谱。通过多种病毒（包膜病毒和非包膜病毒）以及人类可传播性海绵状脑病（TSE）模型评估这些步骤的清除能力和稳健性。
结果
IQYMUNE生产工艺显示出高且稳健的病毒去除能力，相关和模型病毒的整体降低因子（RF）如下：人类免疫缺陷病毒1型（HIV-1）≥14.8对数，牛病毒性腹泻病毒（BVDV）/辛德毕斯病毒≥16.9对数，伪狂犬病病毒（PRV）≥15.7对数，脑心肌炎病毒（EMCV）≥12.8对数，猪细小病毒（PPV）11.0对数。由于辛酸分级分离、阴离子交换色谱和纳滤步骤的互补作用，该工艺对TSE病原体也表现出高去除能力，总体RF≥12.9对数。
结论
病毒和朊病毒清除研究的数据充分支持IQYMUNE的高安全性，对于最小且最具抗性的非包膜病毒PPV的最小降低量为11对数，对于TSE病原体则超过12对数。
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