**INTRODUCTION **
In this guidance, we, FDA, are providing recommendations to sponsors developing human gene therapy products incorporating genome editing (GE) of human somatic cells. Specifically, this guidance provides recommendations regarding information that should be provided in an Investigational New Drug (IND) application in order to assess the safety and quality of the investigational GE product, as required in Title 21 of the Code of Federal Regulations 312.23 (21 CFR 312.23). This includes information on product design, product manufacturing and testing, nonclinical safety assessment, and clinical trial design.
In general, FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.
**BACKGROUND **
The level of interest in human GE as a scientific technology used in the treatment of human disease has increased substantially, and there has been rapid development of gene therapy products incorporating GE. While the potential of such products for the treatment of human disease is clear, the potential risks are not as well understood. To assist in the translation of these products from the bench to clinical trials, this guidance includes recommendations for how to assess the safety and quality of these products and address the potential risks of these products.
For the purpose of this guidance, human GE is a process by which DNA sequences are added, deleted, altered or replaced at specified location(s) in the genome of human somatic cells, ex vivo or in vivo, using nuclease-dependent or nuclease-independent GE technologies. Human gene therapy products incorporating GE are referred to as human GE products throughout this guidance.
FDA evaluates human GE products using a science-based approach weighing the benefits and risks of each product. The benefit-risk profile for each product depends on the proposed indication and patient population, the extent and duration of therapeutic benefit achieved, and the availability of alternative therapeutic options. Some of the specific risks associated with GE approaches include off-target editing, unintended consequences of on-target editing, and the unknown long term effects of on- and off-target editing.
Human GE is a rapidly evolving field and this guidance encompasses FDA’s current thinking regarding the development of human GE products for clinical studies and licensure. As the field evolves, product design advances, and we gain information on the safety of human GE products, we may revise our recommendations to take into account such changes.
To continue reading this article please go to US FDA .