Regulatory Core

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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.