In July 2018, the U.S. Food and Drug Administration (FDA) issued a Draft Guidance for Industry, on Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs). Since the initial FDA gene therapy guidance was implemented in 2008, there have been significant advances in gene therapy. While the draft guidance is currently open only for comments and has not been implemented by the FDA Center for Biologics Evaluation and Research (CBER), it does provide an indication of the Agency’s current thinking regarding the quality information that should be included in an initial IND filed for human gene therapy.
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The guidance defines human gene therapy products as any product that mediates its effects by transcription or translation of transferred genetic material or by altering the host genetic sequence. While CMC information is typically limited in an initial IND, the Agency requires that the sponsor of the IND assures the safety, identity, quality, purity, and strength of the investigational human gene therapy product.
The intent of the draft guidance is to assure the safety and manufacturing control at each stage of development and states that the available CMC information for the initial IND may be limited. However, upon further review of the draft guidance, it appears that for an initial IND, CBER is actually requesting CMC information (e.g., critical process controls, shipping studies, etc.) that are not available until later in development (i.e., Phase 3 or BLA filing).
During the comment period, it is expected that multiple revisions will occur and the CMC information required for a human gene therapy product IND may be reduced. With over hundreds of years of combined regulatory expertise in all phases of quality development and registration, Pearl Pathways is here to help you navigate the confusing and challenging FDA environment for human gene therapy product from an initial IND through the marketing authorization application (i.e., NDA or BLA). Our interaction with both you, the sponsor, and the FDA allows for a collaborative effort providing a clear path to the submission of a regulatory submission that meets the expectations of the Agency and rapid approval for the initiation of your clinical program.
FDA Draft Guidance: https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM610795.pdf