MPI Research, Division of Drug Safety Evaluation, Mattawan, MI 49071, USA.
Syst Biol Reprod Med. 2012 Feb;58(1):23-32. doi: 10.3109/19396368.2011.648821.
The nonhuman primates (NHPs) are used in many areas of biomedical research where their similarities to humans make them exclusively valuable animal models. The use of NHPs in pre-clinical testing is expected to increase due to the increase in the development of biological compounds for therapeutic uses. The regulatory agencies around the world including Food and Drug Administration (FDA) generally requires developmental and reproductive toxicity (DART) testing of all new drugs to be used by women of childbearing age or men of reproductive potential. NHPs are most frequently used for DART testing when commonly used rodents and/or rabbits are not pharmacologically relevant species. Animal studies are unique in that assessment of reproduction and development as DART studies are not performed in controlled clinical trials; therefore, pre-clinical safety assessment forms the basis for risk assessment for marketed drug products. This paper provides a critical evaluation of developmental and reproductive toxicity studies in NHPs. The manuscript will focus on species selection, limitation of International Conference for Harmonization stages (A-F) using NHPs as a test system, study designs, logistical/technical challenges, and strength, and limitations. It will also pinpoint confounding factors inherent to the test system that may complicate the interpretation of the NHP DART data.
非人类灵长类动物（NHPs）在许多生物医学研究领域中被使用，因为它们与人类的相似性使它们成为非常有价值的动物模型。由于治疗用途的生物化合物的开发增加，预计 NHP 将在临床前测试中得到更多的应用。包括美国食品和药物管理局（FDA）在内的世界各地的监管机构通常要求所有拟用于育龄妇女或有生殖潜力的男性的新药进行发育和生殖毒性（DART）测试。当常用的啮齿动物和/或兔子不是药理学相关物种时，最常使用 NHP 进行 DART 测试。动物研究具有独特性，因为作为 DART 研究的生殖和发育评估并未在对照临床试验中进行；因此，临床前安全性评估构成了上市药物产品风险评估的基础。本文对 NHP 的发育和生殖毒性研究进行了批判性评估。本文将重点介绍物种选择、使用 NHP 作为测试系统限制国际协调会议阶段（A-F）、研究设计、后勤/技术挑战以及优势和局限性。它还将指出测试系统固有的混杂因素，这些因素可能会使 NHP DART 数据的解释复杂化。
