Back to: FDA Regulatory Education for Industry (REdI) 2024 Conference – Biologics Track
Presenter
Brian Stultz
Chief, Gene Therapy Branch 2 (GTB2)
Division of Gene Therapy 1 (DGT1)
Office of Gene Therapy CMC (OGT)
Office of Therapeutic Products (OTP)
Center for Biologics Evaluation and Research (CBER)
US Food and Drug Administration (FDA)
Brian Stultz is the Chief of Gene Therapy Branch 2 located in the Office of Gene Therapy CMC, Office of Therapeutic Products, Center for Biologics Evaluation and Research. Brian has over 19 years of experience with cell and gene therapy CMC review including expertise in plasmids, peptides, mRNA, genome editing, and AAV based products. He received a Master of Science with training in Biochemistry and Molecular Biology from the University of Virginia. Since joining the FDA in 2000, Brian worked in the lab of Dr. Hursh publishing multiple papers on the regulation of the TGF-β signaling pathway and identifying critical quality attributes of mesenchymal stem cells (MSCs). In addition to lab research, he participated in reviewing gene therapy CMC and eventually transitioned to full time review of gene therapy products.
Abstract
Brian Stultz, Branch Chief in CBER’s Office of Gene Therapy CMC, presents on regulatory approaches for human somatic genome editing. He defines genome editing as site-specific DNA insertion, deletion, or replacement using nucleases or non-nuclease methods, explaining technologies like CRISPR, base editors, and prime editors. The talk covers potential therapeutic applications, including treating hematologic disorders like sickle cell disease, for which the first genome editing product was approved. Stultz discusses critical CMC considerations for these products, dividing them into directly administered (in vivo) and ex vivo modified cellular products. Key considerations include product design, delivery, component optimization, and rigorous on and off-target editing studies. Ensuring product quality requires qualified starting materials, well-defined processes, and extensive testing, with genome editing components manufactured under phase-appropriate CGMPs. Major safety concerns addressed are off-target editing, unintended biological consequences of on-target editing, chromosomal abnormalities, and immunogenicity. Identifying off-target effects necessitates using orthogonal methods. Stultz highlights FDA guidance and early communication pathways available to sponsors developing these innovative therapies.