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 该核心的目标是制定适当的项目特定的监管策略，定义项目 相对于关键监管问题的里程碑，并支持执行这些策略以满足必要的 里程碑。基因组编辑技术在快速变化的情况下有一些独特的监管挑战 监管景观。尽管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，以有效且适当的解释和使用。 核心员工的丰富发展经验，涵盖了通过高级评估的临床评估 诸如细胞和基因疗法之类的疗法是项目成功的组成部分。核心将利用前进的生物 研究所的弹射计划，该计划员工以里程碑为驱动的方法来支持法规信息 决策并提高临床前发展的步伐和质量。弹射器专注于导航 临床前开发过程中的监管景观，并提供具有可行工具包的工作流程 并制定解决风险的措施。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项目特定技术成熟管道 和个人项目团队，3）监视与监管里程碑有关的进度，以及4）开发文件 需要提高提交的疗法。这些任务的成功完成将桥接至关重要 知识差距，减轻风险，解决监管问题，并促进与FDA的有效沟通。 结果包括一个监管计划，该计划描述了特定的行动，适用的FDA加急标识 程序以及文档的生成，包括互动和预先指示的简报软件包以及IND 提交。监管核心将利用CRISPR Vision计划的独特机会来推进 通过标准化临床前测试方法，这些模块化编辑和输送系统的临床翻译， 包括使用人类多能干细胞的模型，并通过认识到提供的机会 FDA的罕见疾病基因治疗指南的学术翻译科学指导。这是可能的 由于项目和核心之间存在高度的监管协同作用，特别是安全 毒理学，免疫反应和靶向效果等方面。一个项目的许多要素 直接告知对方的开发和顺序的FDA参与，使项目2和3可以基于 从反馈FDA为项目1提供的监管基础。与人类的协同作用 细胞测定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器的安全性。此外，一个模块化的监管方法 监管共同点并阐明了独特的考虑，以加快通往临床的道路 评估稀有疾病和整个领域的非病毒基因组编辑技术。