Regulatory Core

监管核心

• 批准号: 10668165
• 负责人: Cathy Rasmussen
• 金额: $ 22.97万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-16 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668165
• 关键词: Address; Animal Model; Animals; Authorization documentation; Biological Products; Cell Therapy; Cellular Assay; Clinical Trials; Clinical assessments; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communication; Consensus; Data; Development; Documentation; Elements; Eligibility Determination; Ensure; Feedback; Foundations; Generations; Genome; Goals; Human; Immune response; Individual; Inherited; Knowledge; Measures; Medical; Monitor; Outcome; Pharmacologic Substance; Preclinical Testing; Rare Diseases; Recommendation; Regenerative Medicine; Regulatory Affairs; Reporting; Research Project Grants; Resources; Retina; Risk; Safety; Somatic Cell; Standardization; Strategic Planning; System; Technology; Testing; Therapeutic; Toxicology; Translational Research; Vision; Work; authority; clinical translation; experience; first-in-human; gene therapy; genome editing; human pluripotent stem cell; improved; meetings; pre-Investigational New Drug meeting; pre-clinical; preclinical development; product development; programs; research clinical testing; risk mitigation; small molecule; stem cell model; success; synergism; therapeutic development; therapy development; timeline

PROJECT SUMMARY/ABSTRACT - REGULATORY CORE The objectives of this Core are to develop appropriate project-specific regulatory strategies, define project milestones relative to the critical regulatory issues, and support execution of those strategies to meet the requisite milestones. Genome editing technologies have several unique regulatory challenges within a rapidly changing regulatory landscape. While the FDA provides resources to guide preclinical development, these materials generally require a degree of applicable experience for effective and appropriate interpretation and use. The Core staff’s substantial development experience, spanning discovery through clinical evaluation of advanced therapeutics like cell and gene therapies, is integral to project success. The Core will leverage the Forward BIO Institute’s Catapult Program, which employs a milestone-driven approach to support regulatory-informed decisions and improve the pace and quality of preclinical development. Catapult focuses on navigating the regulatory landscape during preclinical development and provides a workflow with an actionable toolkit to identify and develop measures to address risk. The Core’s Tasks are: 1) identify critical regulatory-related deficiencies, 2) develop a comprehensive project-specific technology maturation pipeline in collaboration with the other Cores and individual Project teams, 3) monitor progress related to regulatory milestones, and 4) develop documentation needed to advance a therapy towards IND submission. Successful completion of these Tasks will bridge critical knowledge gaps, mitigate risk, address regulatory concerns, and facilitate effective communication with the FDA. Outcomes include a regulatory plan that delineates specific actions, identification of applicable FDA Expedited Programs, and generation of documents including the INTERACT and pre-IND briefing packages and the IND submission. The Regulatory Core will capitalize on the CRISPR Vision Program’s unique opportunity to advance clinical translation of these modular editing and delivery systems by standardizing preclinical testing approaches, including use of human pluripotent stem cell-based models, and by recognizing the opportunities afforded to academic translational science by the recent FDA guidance on gene therapy for rare disease. This is possible due to the high degree of regulatory synergy that exists between the Projects and Cores, in particular safety aspects such as toxicology, immune response, and on/off-target effects. Numerous elements of one Project directly inform development of the other, and sequential FDA engagement enables Projects 2 and 3 to build on the regulatory foundation established from the feedback FDA provides to Project 1. The synergy with the Human Cell Assay and Large Animal Cores is even more pronounced, as no suitable animal model exists to evaluate safety for these and other somatic cell genome editors. Furthermore, a modular regulatory approach leverages the regulatory commonalities and clarifies the unique considerations, serving to expedite the path to clinical assessment of nonviral genomic editing technologies for rare diseases and the field as a whole.

项目摘要/摘要-监管核心 这个核心的目标是制定适当的特定于项目的监管战略，定义项目 与关键监管问题相关的里程碑，并支持执行这些战略，以满足必要的 里程碑。基因组编辑技术在快速变化的环境中面临着几个独特的监管挑战 监管格局。虽然FDA提供了指导临床前开发的资源，但这些材料 通常需要一定程度的适用经验才能有效和适当地进行解释和使用。这个 核心员工丰富的开发经验，通过对高级 像细胞和基因治疗一样，治疗是项目成功不可或缺的一部分。核心将利用前卫的传记 研究所的弹射计划，采用里程碑驱动的方法来支持监管信息 并提高临床前开发的速度和质量。Catapult专注于导航 并提供了一个带有可操作工具包的工作流程，以确定 并制定应对风险的措施。该核心的任务是：1)确定与监管相关的关键缺陷， 2)与其他核心合作开发全面的具体项目技术成熟管道 和单个项目团队，3)监控与法规里程碑相关的进度，4)开发文档 需要向IND屈服推进一种治疗方法。成功完成这些任务将起到至关重要的桥梁作用 知识差距，降低风险，解决监管问题，并促进与FDA的有效沟通。 结果包括描述具体行动的监管计划，加快确定适用的FDA 方案和文件的生成，包括InterAct和Pre-IND简报包以及IND 呈件。监管核心将利用CRISPR愿景计划的独特机会来推进 通过标准化临床前测试方法对这些模块化编辑和交付系统进行临床翻译， 包括使用基于人类多能干细胞的模型，并通过认识到为 学术翻译科学由FDA最近对罕见疾病的基因治疗指导。这是可能的 由于项目和核心之间存在高度的监管协同，特别是安全 毒理学、免疫反应和靶上/靶外效应等方面。一个项目的多个要素 直接通知其他项目的开发，FDA的顺序参与使项目2和3能够在此基础上进行构建 根据FDA向项目1提供的反馈建立的监管基础。与人类的协同作用 细胞分析和大动物核心更加明显，因为没有合适的动物模型来评估 这些和其他体细胞基因组编辑的安全性。此外，模块化的监管方法利用 监管的共性并澄清了独特的考虑因素，有助于加快临床进程 评估针对罕见疾病和整个领域的非病毒基因组编辑技术。