A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development
A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development
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DOI：
10.1016/j.yrtph.2007.11.009
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Chapman, Kathryn
中科院分区：
文献类型：
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作者：
Robinson, Sally;Delongeas, Jean-Luc;Chapman, Kathryn
监管指南表明，对于供人类使用的药物，动物急性毒性研究被认为是必要的。这是唯一将致死率作为终点的研究类型。这些研究通常在啮齿类动物中进行，以支持新药的营销并确定最低致死剂量。一项由 18 家公司组成的欧洲倡议对急性毒性研究进行了循证审查，并评估了所生成数据的价值。共享 74 种化合物的临床前和临床信息。分析表明，急性毒性数据并未用于（i）终止药物开发（ii）支持动物重复剂量研究的剂量选择或（iii）在人类首次临床试验中设定剂量。工作组的结论是，在首次人体临床试验之前不需要进行急性毒性研究。相反，可以从其他研究中获得信息，这些研究是在与人类更相关的剂量下进行的，并且已经成为药物开发不可或缺的一部分。该结论已与美国、日本和欧洲监管机构的代表进行了讨论并达成一致。 (C) 2007 Elsevier Inc. 保留所有权利。
Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs-from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe. (C) 2007 Elsevier Inc. All rights reserved.