Center for Environmental Health Sciences, Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi (B.L.F.K.); Charles River Laboratories, Inc., Horsham, Pennsylvania (A.M.H.); Retired, National Center for Toxicological Research, Jefferson, Arkansas (W.S.); University of Georgia, Athens, Georgia (M.A.S.); Department of Pharmacological and Biomolecular Sciences, 'Rodolfo Paoletti' Università degli Studi di Milano, Milan, Italy (E.C.); US Environmental Protection Agency, Research Triangle Park, North Carolina (T.B.K.); Dow, Inc., Midland, Michigan (M.S.M.); Howard University College of Medicine, Washington DC (S.K.S.); Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, Maryland (S.C.F.); Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts (M.H.R.); and National Center for Toxicological Research, US Food and Drug Administration, Silver Spring, Maryland (D.L.M.)
Center for Environmental Health Sciences, Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi (B.L.F.K.); Charles River Laboratories, Inc., Horsham, Pennsylvania (A.M.H.); Retired, National Center for Toxicological Research, Jefferson, Arkansas (W.S.); University of Georgia, Athens, Georgia (M.A.S.); Department of Pharmacological and Biomolecular Sciences, 'Rodolfo Paoletti' Università degli Studi di Milano, Milan, Italy (E.C.); US Environmental Protection Agency, Research Triangle Park, North Carolina (T.B.K.); Dow, Inc., Midland, Michigan (M.S.M.); Howard University College of Medicine, Washington DC (S.K.S.); Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, Maryland (S.C.F.); Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts (M.H.R.); and National Center for Toxicological Research, US Food and Drug Administration, Silver Spring, Maryland (D.L.M.).
Pharmacol Rev. 2024 Feb 13;76(2):251-266. doi: 10.1124/pharmrev.123.000967.
Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used to understand the effects and mechanisms of drugs or chemicals, with specific focus on applying the 3Rs. Although progress has been made in several areas with NAMs, complete replacement of animal models with NAMs is not yet attainable. The road to NAMs requires additional development, increased use, and, for regulatory decision making, usually formal validation. Moreover, it is likely that replacement of animal models with NAMs will require multiple assays to ensure sufficient biologic coverage. The purpose of this manuscript is to provide a balanced view of the current state of the use of animal models and NAMs as approaches to development, safety, efficacy, and toxicity testing of drugs and chemicals. Animals do not provide all needed information nor do NAMs, but each can elucidate key pieces of the puzzle of human and animal biology and contribute to the goal of protecting human and animal health. SIGNIFICANCE STATEMENT: Data from traditional animal studies have predominantly been used to inform human health safety and efficacy. Although it is unlikely that all animal studies will be able to be replaced, with the continued advancement in new approach methods (NAMs), it is possible that sometime in the future, NAMs will likely be an important component by which the discovery, efficacy, and toxicity testing of drugs and chemicals is conducted and regulatory decisions are made.
动物和动物模型对于我们目前理解人类和动物生物学，包括生理学、药理学、生物化学和疾病病理学，具有不可估量的价值。然而，人们越来越担心在基础生物医学、药理学和监管研究中继续使用动物来为药物和化学品提供安全性评估。有人担心，动物不能提供足够的关于毒性和/或疗效的信息，以保护目标人群，因此科学家们正在利用替代、减少和优化（3R）的原则，并增加新方法（NAMs）的开发和应用。NAMs 是指用于了解药物或化学品的作用和机制的任何技术、方法、方法或检测方法，特别注重应用 3R。尽管 NAMs 在几个领域取得了进展，但完全用 NAMs 替代动物模型还无法实现。实现 NAMs 的道路需要进一步开发、更多的应用，并且对于监管决策，通常需要正式验证。此外，用 NAMs 替代动物模型可能需要进行多个检测，以确保充分的生物学覆盖。本文的目的是提供一种平衡的观点，即当前使用动物模型和 NAMs 作为药物和化学品开发、安全性、疗效和毒性测试的方法的现状。动物不能提供所有需要的信息，NAMs 也不能，但每个都可以阐明人类和动物生物学的关键部分，并有助于保护人类和动物健康的目标。意义声明：传统动物研究的数据主要用于为人类健康安全性和疗效提供信息。尽管不太可能所有的动物研究都能够被取代，但随着新方法（NAMs）的不断进步，未来某个时候，NAMs 很可能成为药物和化学品的发现、疗效和毒性测试以及监管决策的重要组成部分。
