Solomon Howard M, Makris Susan L, Alsaid Hasan, Bermudez Oscar, Beyer Bruce K, Chen Antong, Chen Connie L, Chen Zhou, Chmielewski Gary, DeLise Anthony M, de Schaepdrijver Luc, Dogdas Belma, French Julian, Harrouk Wafa, Helfgott Jonathan, Henkelman R Mark, Hesterman Jacob, Hew Kok-Wah, Hoberman Alan, Lo Cecilia W, McDougal Andrew, Minck Daniel R, Scott Lelia, Stewart Jane, Sutherland Vicki, Tatiparthi Arun K, Winkelmann Christopher T, Wise L David, Wood Sandra L, Ying Xiaoyou
GlaxoSmithKline, King of Prussia, PA, United States.
U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, DC, United States.
Regul Toxicol Pharmacol. 2016 Jun;77:100-8. doi: 10.1016/j.yrtph.2016.02.018. Epub 2016 Feb 27.
During the past two decades the use and refinements of imaging modalities have markedly increased making it possible to image embryos and fetuses used in pivotal nonclinical studies submitted to regulatory agencies. Implementing these technologies into the Good Laboratory Practice environment requires rigorous testing, validation, and documentation to ensure the reproducibility of data. A workshop on current practices and regulatory requirements was held with the goal of defining minimal criteria for the proper implementation of these technologies and subsequent submission to regulatory agencies. Micro-computed tomography (micro-CT) is especially well suited for high-throughput evaluations, and is gaining popularity to evaluate fetal skeletons to assess the potential developmental toxicity of test agents. This workshop was convened to help scientists in the developmental toxicology field understand and apply micro-CT technology to nonclinical toxicology studies and facilitate the regulatory acceptance of imaging data. Presentations and workshop discussions covered: (1) principles of micro-CT fetal imaging; (2) concordance of findings with conventional skeletal evaluations; and (3) regulatory requirements for validating the system. Establishing these requirements for micro-CT examination can provide a path forward for laboratories considering implementing this technology and provide regulatory agencies with a basis to consider the acceptability of data generated via this technology.
在过去二十年中，成像技术的应用和改进显著增加，使得对提交给监管机构的关键非临床研究中使用的胚胎和胎儿进行成像成为可能。将这些技术应用于良好实验室规范环境需要进行严格的测试、验证和记录，以确保数据的可重复性。举办了一次关于当前实践和监管要求的研讨会，目的是确定正确应用这些技术并随后提交给监管机构的最低标准。微计算机断层扫描（micro-CT）特别适合高通量评估，并且在评估胎儿骨骼以评估受试物潜在发育毒性方面越来越受欢迎。召开这次研讨会是为了帮助发育毒理学领域的科学家理解并将micro-CT技术应用于非临床毒理学研究，并促进监管机构对成像数据的接受。研讨会的报告和讨论内容包括：（1）micro-CT胎儿成像的原理；（2）结果与传统骨骼评估的一致性；（3）系统验证的监管要求。确定这些micro-CT检查要求可为考虑应用该技术的实验室提供前进方向，并为监管机构提供依据，以考虑通过该技术生成的数据的可接受性。
