Alternatives to Monkey Reproductive Toxicology Testing for Biotherapeutics.

IF 1.2 4区 医学 Q4 PHARMACOLOGY & PHARMACY
International Journal of Toxicology Pub Date : 2023-12-01 Epub Date: 2023-09-15 DOI:10.1177/10915818231200859
Alan M Hoberman, Kazushige Maki, Fumito Mikashima, Misaki Naota, Ronald L Wange, Janice A Lansita, Shawna L Weis
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引用次数: 0

Abstract

Embryofetal toxicity studies are conducted to support inclusion of women of childbearing potential in clinical trials and to support labeling for the marketed pharmaceutical product. For biopharmaceuticals, which frequently lack activity in the rodent or rabbit, the nonhuman primate is the standard model to evaluate embryofetal toxicity. These studies have become increasingly challenging to conduct due to the small number of facilities capable of performing them and a shortage of sexually mature monkeys. The low number of animals per group and the high rate of spontaneous abortion in cynomolgus monkeys further complicate interpretation of the data. Recent FDA guidance has proposed a weight of evidence (WoE) approach to support product labeling for reproductive toxicity of products intended to be used for the treatment of cancer (Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations), an approach that has also supported the approval of biotherapeutics for non-cancer indications. Considerations to determine the appropriateness and content of a WoE approach to support product labeling for embryofetal risk include known class effects in humans; findings from genetically modified animals with or without drug administration; information from surrogate compounds; literature-based assessments about the developmental role of the pharmaceutical target; and the anticipated exposure during embryofetal development. This paper summarizes the content of a session presented at the 42nd annual meeting at the American College of Toxicology, which explored the conditions under which alternative approaches may be appropriate to support product labeling for reproductive risk, and how sponsors can best justify the use of this approach.

用于生物治疗的猴子生殖毒理学测试的替代品。
进行胚胎-胎儿毒性研究是为了支持将有生育潜力的妇女纳入临床试验,并支持上市药品的标签。对于在啮齿类动物或兔子身上经常缺乏活性的生物制药来说,非人灵长类动物是评估胚胎-胎儿毒性的标准模型。由于能够进行这些研究的设施数量少,性成熟猴子短缺,这些研究变得越来越具有挑战性。食蟹猴每组动物数量少,自然流产率高,这进一步使数据的解释复杂化。美国食品和药物管理局最近的指导意见提出了一种证据权重(WoE)方法,以支持用于治疗癌症的产品的生殖毒性的产品标签(肿瘤药物:生殖毒性测试和标签建议),这种方法也支持批准非癌症适应症的生物治疗药物。确定支持胚胎-胎儿风险产品标签的WoE方法的适当性和内容的考虑因素包括已知的人类类别效应;转基因动物给药或不给药的研究结果;来自替代化合物的信息;关于药物靶点的发展作用的文献评估;以及胚胎-胎儿发育期间的预期暴露。本文总结了在美国毒理学学院第42届年会上举行的一次会议的内容,该会议探讨了替代方法可能适用于支持生殖风险产品标签的条件,以及赞助商如何最好地证明使用这种方法的合理性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.40
自引率
4.50%
发文量
53
审稿时长
4.5 months
期刊介绍: The International Journal of Toxicology publishes timely, peer-reviewed papers on current topics important to toxicologists. Six bi-monthly issues cover a wide range of topics, including contemporary issues in toxicology, safety assessments, novel approaches to toxicological testing, mechanisms of toxicity, biomarkers, and risk assessment. The Journal also publishes invited reviews on contemporary topics, and features articles based on symposia. In addition, supplemental issues are routinely published on various special topics, including three supplements devoted to contributions from the Cosmetic Review Expert Panel.
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