Virus Susceptibility of Chinese Hamster Ovary (CHO) Cells and Detection of Viral Contaminations by Adventitious Agent Testing
Virus Susceptibility of Chinese Hamster Ovary (CHO) Cells and Detection of Viral Contaminations by Adventitious Agent Testing
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DOI：
10.1002/bit.22723
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发表时间：
2010-07-01
影响因子：
3.8
通讯作者：
Kreil, Thomas R.
中科院分区：
文献类型：
--
作者：
Berting, Andreas;Farcet, Maria R.;Kreil, Thomas R.
生物制药在治疗各种疾病方面发挥着越来越重要的作用。与其生产相关的一个仍然令人担忧的问题是，可能会在其制造过程中引入不定性剂，这可能会危及产品的病原体安全性，并可能导致重要医疗用品的缺货情况。为了确保生物疗法的安全，监管指南要求对批量收获的不定性剂进行检测(AAT)。AAT是一种故意混杂的分析程序，理想情况下，它被开发来指示任何病毒污染物的存在。中国仓鼠卵巢(CHO)细胞是用于生产生物药物的最重要的细胞系之一，虽然CHO细胞已发生病毒感染，但其病毒敏感性的系统筛查从未发表过。我们调查了CHO细胞对14种不同病毒感染的敏感性，包括12个科和代表或与先前报道的生产细胞感染有关的特定物种的成员。根据我们的结果，四种不同的感染结果是：(I)诱导或不诱导细胞病变效应和(Ii)在CHO细胞中复制的能力。我们的结果表明，由于CHO细胞对病毒的敏感性和常规，目前的AAT对于能够在CHO细胞中复制的病毒的检测是有效的。在大量收获的情况下，我们的结果为CHO细胞衍生生物制药Biotechnol非常高的安全边际提供了保证。比昂斯。2010年；106 598-607(C)2010威利期刊公司。
Biopharmaceuticals are of increasing importance in the treatment of a variety of diseases. A remaining concern associated with their production is the potential introduction of adventitious agents into their manufacturing process, which may compromise the pathogen safety of a product and potentially cause stock-out situations for important medical supplies To ensure the safety of biological therapeutics, regulatory guidance requires adventitious agent testing (AAT) of the bulk harvest. AAT is a deliberately promiscuous assay procedure which has been developed to indicate, ideally, the presence of any viral contaminant. One of the most important cell lines used in the production of biopharmaceuticals is Chinese hamster ovary (CHO) cells and while viral infections of CHO cells have occurred, a systematic screen of their virus susceptibility has never been published We investigated the susceptibility of CHO cells to infection by 14 different viruses, including members of 12 families and representatives or the very species that were implicated in previously reported production cell infections Based on our results, four different infection outcomes were factors (I) the induction, or not, of a cytopathic effect and (II) the ability, or not, to replicate in CHO cells. Our results demonstrate that the current AAT is effective for the detection of viruses which are able to replicate in CHO cells Due to the restricted virus susceptibility of CHO cells and the routine. AAT of bulk harvests, our results provide re-assurance for the very high safety margins of CHO cell-derived biopharmaceuticals Biotechnol. Bioeng. 2010; 106 598-607 (C) 2010 Wiley Periodicals, Inc.