Human Gene Therapy Products: Incorporating Human Genome Editing Guidance for Industry: Part 1 

Human Gene Therapy Products: Incorporating Human Genome Editing Guidance for Industry: Part 1 

The FDA recently released guidance (FDA- Human Gene Therapy Products: Incorporating Human Genome Editing Guidance for Industry (Jan 2024)) related to the development and manufacturing of human gene therapy products incorporating genome editing (GE) in human somatic cells As the level of interest in human GE technology continues to rise, the FDA is concerned about the unique risks of these technologies, especially off-target editing, unintended consequences of on-target editing, and unknown long-term effects of both on- and off-target editing. The guidance has specific suggestions for how to choose a method, how to set up a clinical trial, and what sponsors should include in an Investigational New Drug (IND) application. When it comes to product design, in addition to method selection, the FDA has recommendations on the type and level of genomic modification and the delivery methods for genome editing components. 

This guidance gives specific recommendations relating to Chemistry, Manufacturing, and Controls (CMC) for DE drug substance (DS) or DE drug product (DP) and provides guidance on how to classify as DS or DP. The guidance is broad and offers the FDA’s current thinking on CMC issues, such as GE component design, GE component manufacture and testing, and drug product (DP) manufacture and testing. This guidance is not designed to be stand-alone CMC guidance but builds on previous guidance for cell and gene therapy (CGT) products. 

The general CMC considerations for product manufacturing, testing, and release of human GE products are the same as those previously described in the FDA’s guidance entitled “Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs): Guidance for Industry,” January 2020.  

The safety of GE therapies is the focus of the new guidance. It covers all aspects of non-clinical proof of concept studies, including: scientific justification and feasibility; non-clinical safety studies; risk identification and safety assessments; biodistribution assessments; product evaluations; and activity and immunogenicity studies. Turning to clinical studies, the FDA is concerned not only with the risks associated with the GE product itself but also with the risks associated with GE in general, such as off-target editing and unintended consequences. It lays out a comprehensive list of recommendations to address those issues.  

The guidance is comprehensive and complex (you can read the entire document here). Windshire recommends studying the guidance closely and putting systems in place to ensure appropriate compliance with these recommendations. We also echo the FDA’s advice to communicate with the FDA early in the product development process and stay in close contact as your GE program progresses.  

We will provide more information on this guidance, especially on how it impacts CMC, in upcoming posts. In the meantime, please reach out by email at info@windshire.com or call +1 844-686-5750 if you need our experts to assist with your development needs. #consultant #FDA #guidance #CGT #geneediting #CMC #development