Avila Amy M, Bebenek Ilona, Mendrick Donna L, Peretz Jackye, Yao Jia, Brown Paul C
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, United States.
National Center for Toxicological Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, United States.
Regul Toxicol Pharmacol. 2023 Mar;139:105345. doi: 10.1016/j.yrtph.2023.105345. Epub 2023 Feb 4.
Previously, we provided an FDA/CDER perspective on nonclinical testing strategies and briefly discussed the opportunities and challenges of using new approach methodologies (NAMs) in drug development, especially for regulatory purposes. To facilitate the integration of NAMs into nonclinical regulatory testing, we surveyed the CDER Pharmacology/Toxicology community to identify the nonclinical challenges faced by CDER review staff, including gaps and areas of concern underserved by current nonclinical testing approaches, and to understand how development of NAMs with specific contexts of use (COUs) could potentially alleviate them. Survey outcomes were coalesced into CDER-identified needs for which NAMs with specific COUs could potentially be developed to address gaps and challenges in nonclinical safety assessments. We also discussed the current FDA procedure for validation and qualification of NAMs intended to inform regulatory decisions. This manuscript is intended to facilitate productive discussions and collaborations with regulatory, government, and academic stakeholders within the drug development community regarding the development and regulatory use of NAMs and their role in safety and efficacy assessment of pharmaceuticals.
此前，我们从美国食品药品监督管理局药品评价和研究中心（FDA/CDER）的角度阐述了非临床测试策略，并简要讨论了在药物研发中使用新方法学（NAMs）的机遇与挑战，特别是出于监管目的的使用情况。为促进将新方法学整合到非临床监管测试中，我们对CDER的药理学/毒理学团队进行了调查，以确定CDER审评人员面临的非临床挑战，包括当前非临床测试方法未充分覆盖的差距和关注点领域，并了解针对特定使用背景（COUs）开发新方法学如何有可能缓解这些挑战。调查结果汇总为CDER确定的需求，针对这些需求，有可能开发出具有特定使用背景的新方法学，以解决非临床安全性评估中的差距和挑战。我们还讨论了FDA目前用于验证和鉴定旨在为监管决策提供依据的新方法学的程序。本手稿旨在促进与药物研发界的监管、政府和学术利益相关者就新方法学的开发和监管用途及其在药品安全性和有效性评估中的作用展开富有成效的讨论与合作。
