Abstract：
Following the European Commission decision to develop a roadmap to phase out animal testing and the signing of the US Modernisation Act, there is additional pressure on regulators and the pharmaceutical industry to abandon animal experimentation in safety testing. Often, endeavours already made by governments, regulators, trade associations, and industry to replace, reduce and refine animal experimentation (3Rs) are unnoticed. Herein, we review such endeavours to promote wider application and acceptance of 3Rs. ICH guidelines have stated 3Rs objectives and have enjoyed many successes driven by global consensus. Initiatives driven by US and European regulators such as the removal of the Abnormal Toxicity Test are neutralised by reticent regional regulators. Stream-lined testing requirements have been proposed for new modalities, oncology, impurity management and animal pharmacokinetics/metabolism. Use of virtual controls, value of the second toxicity species, information sharing and expectations for life-threatening diseases, human specific or well-characterised targets are currently being scrutinised. Despite much effort, progress falls short of the ambitious intent of decisionmakers. From a clinical safety and litigation perspective pharmaceutical companies and regulators are reluctant to step away from current paradigms unless replacement approaches are validated and globally accepted. Such consensus has historically been best achieved through ICH initiatives.
摘要：
在欧盟委员会决定制定逐步淘汰动物试验的路线图并签署《美国现代化法案》之后，监管机构和制药行业面临额外的压力，要求他们放弃安全测试中的动物实验。通常,政府已经做出的努力，监管者,行业协会,和工业来取代，减少和改进动物实验(3Rs)是被忽视的。在这里，我们会检讨这些努力，以促进更广泛的应用和接受3R。ICH指南提出了3Rs目标，并在全球共识的推动下取得了许多成功。由美国和欧洲监管机构推动的举措，如取消异常毒性测试，被沉默寡言的区域监管机构中和。对新模式提出了流线测试要求，肿瘤学,杂质管理和动物药代动力学/代谢。使用虚拟控件，第二毒性物种的价值，信息共享和对危及生命的疾病的期望，目前正在审查人类特定或特征明确的目标。尽管付出了很多努力,进展达不到决策者的雄心勃勃的意图。从临床安全和诉讼的角度来看，制药公司和监管机构不愿放弃当前的范式，除非替代方法得到验证和全球接受。历史上，这种共识最好通过ICH倡议来实现。
