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.

项目概要/摘要-监管核心 本核心的目标是制定适当的项目特定监管策略， 与关键监管问题相关的里程碑，并支持这些战略的执行，以满足 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提供资源来指导临床前开发， 通常需要一定程度的适用经验，以便有效和适当地解释和使用。的 核心员工的丰富开发经验，通过先进的临床评价跨越发现 细胞和基因疗法等治疗方法是项目成功的关键。核心将利用Forward BIO 研究所的弹射器计划，采用里程碑驱动的方法，以支持监管知情 决策，并提高临床前开发的速度和质量。Catapult专注于导航 在临床前开发过程中的监管环境，并提供了一个具有可操作工具包的工作流程， 并制定应对风险的措施。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，开发全面的特定项目技术成熟管道 和单个项目团队，3）监控与监管里程碑相关的进度，以及4）编制文档 需要将治疗推向IND提交。成功完成这些任务将在关键的 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，确定适用的FDA加速 程序和文件生成，包括INTERACT和IND前简报包以及IND 成绩.监管核心将利用CRISPR愿景计划的独特机会， 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，并认识到 最近FDA关于罕见疾病基因治疗的指导，这是可能 由于项目和核心之间存在高度的监管协同作用，特别是安全方面， 例如毒理学、免疫应答和靶向/脱靶效应。一个项目的多个要素 直接为其他项目的开发提供信息，FDA的连续参与使项目2和项目3能够建立在 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 细胞试验和大型动物核心甚至更明显，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，模块化监管方法利用 监管共性，并阐明了独特的考虑因素，有助于加快临床路径 评估用于罕见疾病和整个领域的非病毒基因组编辑技术。