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.

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对人类和动物生物学（包括生理学、药理学、生物化学和疾病病理学）的理解具有无价的价值。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提供药物和化学品的安全评估。人们担心动物无法提供足够的有关毒性和/或功效的信息来保护目标人群，因此科学家们正在利用替代、减少和细化（3R）的原则，并增加新方法的开发和应用（ NAM）。 NAM 是用于了解药物或化学品的作用和机制的任何技术、方法、方法或测定，特别注重应用 3R。尽管 NAM 在多个领域取得了进展，但用 NAM 完全替代动物模型尚无法实现。通往 NAM 的道路需要额外的开发、增加使用，并且对于监管决策来说，通常还需要正式验证。此外，用 NAM 替代动物模型可能需要进行多次测定以确保足够的生物学覆盖率。本手稿的目的是对动物模型和 NAM 作为药物和化学品的开发、安全性、有效性和毒性测试方法的使用现状提供一个平衡的观点。动物和 NAM 都不能提供所有需要的信息，但它们都可以阐明人类和动物生物学难题的关键部分，并为保护人类和动物健康的目标做出贡献。

传统动物研究的数据主要用于告知人类健康安全性和有效性。尽管不可能取代所有动物研究，但随着新方法 (NAM) 的不断进步，NAM 可能在未来的某个时候成为发现、功效、对药物和化学品进行毒性测试并做出监管决定。