Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies
Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies
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DOI：
10.1111/j.1537-2995.2009.02222.x
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发表时间：
2009-09-01
期刊：
影响因子：
2.9
通讯作者：
Poelsler, Gerhard
中科院分区：
文献类型：
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作者：
Dichtelmueller, Herbert O.;Biesert, Lothar;Poelsler, Gerhard
背景：溶剂/洗涤剂（S/D）处理是一种成熟的病毒灭活技术，已应用于从人血浆中提取的医药产品的生产超过20年。从7家血浆蛋白治疗协会成员公司收集的S/D治疗包膜病毒灭活的数据证明了这种病毒灭活方法的稳健性、可靠性和有效性。研究设计和方法：308项研究的结果反映了生产条件以及明显超出产品释放规范的技术变量，对病毒灭活进行了评估，包括不同的溶剂和洗涤剂组合（三（正丁基）磷酸[TNBP]/Tween 80， TNBP/Triton X-100, TNBP/Na-cholate）和不同的产品（因子[F] VIII， fix，静脉注射和肌肉注射免疫球蛋白）。结果：产品类别、工艺温度、蛋白浓度和pH值对病毒灭活均无显著影响。一个看起来很关键的变量是溶剂和洗涤剂的浓度。结论：本文提供的数据表明，S/D处理对广泛的包膜测试病毒和工艺变量的病毒灭活具有稳健性。我们的数据证实了这样一个事实，即自引入S/D治疗以来，未报告许可的血浆衍生物传播病毒，如人类免疫缺陷病毒、乙型肝炎病毒、丙型肝炎病毒或其他包膜病毒。
BACKGROUND: Solvent/detergent (S/D) treatment is an established virus inactivation technology that has been applied in the manufacture of medicinal products derived from human plasma for more than 20 years. Data on the inactivation of enveloped viruses by S/D treatment collected from seven Plasma Protein Therapeutics Association member companies demonstrate the robustness, reliability, and efficacy of this virus inactivation method.STUDY DESIGN AND METHODS: The results from 308 studies reflecting production conditions as well as technical variables significantly beyond the product release specification were evaluated for virus inactivation, comprising different combinations of solvent and detergent (tri(n-butyl) phosphate [TNBP]/Tween 80, TNBP/Triton X-100, TNBP/Na-cholate) and different products (Factor [F] VIII, F IX, and intravenous and intramuscular immunoglobulins).RESULTS: Neither product class, process temperature, protein concentration, nor pH value has a significant impact on virus inactivation. A variable that did appear to be critical was the concentration of solvent and detergent.CONCLUSION: The data presented here demonstrate the robustness of virus inactivation by S/D treatment for a broad spectrum of enveloped test viruses and process variables. Our data substantiate the fact that no transmission of viruses such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or of other enveloped viruses was reported for licensed plasma derivatives since the introduction of S/D treatment.