Offering Guidance for Translation

Scientists love a challenge. But for developers of cellular and gene therapy (CGT) products, understanding the scope of preclinical testing needed to support early-phase clinical trials can be daunting. In addition, these diverse and complex products often pose safety concerns that cannot be appropriately evaluated with traditional, standardized approaches to preclinical evaluation of small-molecule drugs and biologics. To help developers address these concerns, the U.S. Food and Drug Administration (FDA) has published a draft guidance for the preclinical assessment of investigational CGT products. This guidance clarifies current regulatory expectations for preclinical information used to support human clinical trials and license application. The draft guidance offers recommendations on the substance and scope of preclinical information needed to support clinical trials for multiple investigational product types, including cellular therapies, gene therapies, therapeutic vaccines, xenotransplantation products, and certain biologic-device combination products (such as cellularized scaffolds) regulated by the Office of Cellular, Tissue, and Gene Therapies (OCTGT). General areas of focus include selection of appropriate animal species and models of disease or injury and the conduct of proof-of-concept and toxicology studies. The guidance also highlights specific safety concerns for CGT products, such as tumorigenic potential for some cellular therapy products, and provides recommendations on approaches to their evaluation. Recommendations are presented in the context of designing preclinical programs that help define the risk-benefit profiles of investigational products in order to justify further testing in humans. This draft guidance, when finalized, will supersede the preclinical recommendations issued in a previous FDA guidance ([www.fda.gov/Drugs/ScienceResearch/ResearchAreas/ucm072987.htm][1]) and is not intended to provide a standardized or “cookbook” approach to the preclinical assessment of investigational CGT products. Rather, this guidance encourages a flexible and science-based approach to preclinical testing in which the kind, duration, and scope of testing are tailored for each product and target clinical indication. In recognizing the importance of product-specific, case-by-case application for the CGT products and the inherent challenges this poses, this guidance encourages early communication between product developers and the OCTGT pharmacology and toxicology review staff. In addition, the guidance emphasizes incorporation of the “3 Rs” principles (reduction, refinement, and replacement of animal use) in preclinical testing programs. Publication of this draft guidance signifies FDA’s continuing effort to engage CGT product developers to help facilitate the safe development of these emerging therapies. Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products; [[Full Text] ][2] [1]: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/ucm072987.htm [2]: http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM329861.pdf