Jan Turner, Pandora Pound, Carla Owen, Isobel Hutchinson, Marina Hop, David Y S Chau, Lady V Barrios Silva, Mike Coleman, Audrey Dubourg, Lorna W Harries, Victoria Hutter, J Gerry Kenna, Volker M Lauschke, Winfried Neuhaus, Clive Roper, Paul B Watkins, Jonathan Welch, Laura R Alvarez, Katy Taylor
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引用次数: 0
摘要
基于人体生物学的新方法(NAMs)能够评估药物和其他化学品的不良生物效应。然而,目前尚不清楚在药物开发过程中应如何使用新方法来改进人体安全性评估。我们与 13 位国际专家(监管人员、临床前科学家和 NAMs 开发人员)举行了 5 次系列研讨会,以确定可行的 NAMs,并讨论如何在特定的安全评估环境中加以利用。与会者绘制了四张 "地图",说明如何在肝脏、呼吸系统、心血管系统和中枢神经系统的安全性评估中利用非杀伤性物质。每张地图都显示了测量的相关终点和使用的工具(如细胞、化验、平台),并强调了仍需进一步开发和验证 NAMs 的差距。每张地图都针对该器官系统安全评估的基本科学要求,为用户选择适当的 NAM 提供指导。除了绘制地图之外,与会者还就鼓励在药物开发过程中更多地采用 NAM 并将其纳入监管指南提出了建议。其中一项具体建议是,制药公司在内部如何使用 NAM 方面应该更加透明。除了为四个器官系统提供指导外,地图还提供了一个模板,可用于其他器官的安全性测试。此外,将其转换为交互式格式将使用户能够深入了解回答特定科学和监管问题所需的细节。
Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment.
New approach methodologies (NAMs) based on human biology enable the assessment of adverse biological effects of pharmaceuticals and other chemicals. Currently, however, it is unclear how NAMs should be used during drug development to improve human safety evaluation. A series of 5 workshops with 13 international experts (regulators, preclinical scientists, and NAMs developers) was conducted to identify feasible NAMs and to discuss how to exploit them in specific safety assessment contexts. Participants generated four “maps” of how NAMs can be exploited in the safety assessment of the liver, respiratory, cardiovascular, and central nervous systems. Each map shows relevant endpoints measured and tools used (e.g., cells, assays, platforms), and highlights gaps where further development and validation of NAMs remains necessary. Each map addresses the fundamental scientific requirements for the safety assessment of that organ system, providing users with guidance on the selection of appropriate NAMs. In addition to generating the maps, participants offered suggestions for encouraging greater NAM adoption within drug development and their inclusion in regulatory guidelines. A specific recommendation was that pharmaceutical companies should be more transparent about how they use NAMs in-house. As well as giving guidance for the four organ systems, the maps provide a template that could be used for additional organ safety testing contexts. Moreover, their conversion to an interactive format would enable users to drill down to the detail necessary to answer specific scientific and regulatory questions.
期刊介绍:
ALTEX publishes original articles, short communications, reviews, as well as news and comments and meeting reports. Manuscripts submitted to ALTEX are evaluated by two expert reviewers. The evaluation takes into account the scientific merit of a manuscript and its contribution to animal welfare and the 3R principle.