Comparison of pyrogen assays by testing products exhibiting low endotoxin recovery.

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Altex-Alternatives To Animal Experimentation Pub Date : 2023-01-01 DOI:10.14573/altex.2202021
Tammy L Thurman, Carol J Lahti, Jeanne M Mateffy, Ren-Yo Forng, Friedrich von Wintzingerode, Lindsey M Silva, Sven M Deutschmann, Ned Mozier
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引用次数: 2

Abstract

The use of pyrogen tests to assess the risk of endotoxin in biological products has increased recently due to concerns of some regulatory authorities about products exhibiting low endotoxin recovery (LER). Manufacturers increasingly seek to reduce the use of animals unless essential to assure patient safety. The current study compares the ability of the monocyte activation test (MAT) and the bacterial endotoxin test (BET) to the rabbit pyrogen test (RPT) to detect endotoxin spikes in samples of products shown to exhibit LER. Product samples or water were spiked with endotoxin and held for three days or tested immediately in the BET, the RPT, and two variations of the MAT at the same time. Results show high sensitivity to endotoxin of both the BET and MAT, and much lower sensitivity of the RPT, indicating that much higher levels of reference standard endotoxin are required to induce pyrogenicity in the RPT than the 5 endotoxin units (EU) per kg common threshold. The results of the BET and MAT correlated well for the detection of endotoxin spike in water. We also show that LER (masking of endotoxin) found in the BET is also seen in the MAT and RPT, suggesting that the products themselves elicit a biological inactivation of spiked endotoxin over time, thereby rendering it less or non-pyrogenic. We conclude that the non-animal MAT option is a suitable replacement for the RPT to measure spiked endotoxin in biopharmaceuticals.

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内毒素回收率低的产品热原测定的比较。
最近,由于一些监管机构对内毒素回收率低的产品的担忧,热原试验用于评估生物制品中内毒素风险的使用有所增加。制造商越来越多地寻求减少动物的使用,除非有必要确保病人的安全。目前的研究比较了单核细胞活化试验(MAT)和细菌内毒素试验(BET)与兔热原试验(RPT)在显示有LER的产品样品中检测内毒素峰值的能力。产品样品或水中加入内毒素,保存三天或立即在BET, RPT和两种变体MAT中同时进行测试。结果表明,BET和MAT对内毒素的敏感性都很高,而RPT的敏感性要低得多,这表明RPT诱导热原性所需的参考标准内毒素水平远高于每公斤5个内毒素单位(EU)的共同阈值。BET法和MAT法检测水体中内毒素峰值的结果具有良好的相关性。我们还发现,在BET中发现的LER(内毒素掩蔽)也出现在MAT和RPT中,这表明随着时间的推移,产品本身会引起加钉内毒素的生物失活,从而使其减少或不产生热原性。我们得出的结论是,非动物MAT选项是RPT测量生物制药中加标内毒素的合适替代品。
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来源期刊
Altex-Alternatives To Animal Experimentation
Altex-Alternatives To Animal Experimentation MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
7.70
自引率
8.90%
发文量
89
审稿时长
2 months
期刊介绍: ALTEX publishes original articles, short communications, reviews, as well as news and comments and meeting reports. Manuscripts submitted to ALTEX are evaluated by two expert reviewers. The evaluation takes into account the scientific merit of a manuscript and its contribution to animal welfare and the 3R principle.
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