Description
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.
Scope & Applicability
Product Classes
5Specific category for CMC guidance
Used when human GE product is not informative due to species differences
Subject of the guidance document
Drug product requiring potency testing and biological modification assessment
Products treating multiple patients requiring additional testing
Stakeholders
1Entity responsible for submitting applications under section 524B
Regulatory Context
Attributes
3Frequency of editing or number of cells edited needed for effect
Mechanism of Action used to support study population choice
A functional role of sodium in food
Identified Hazards
Hazards
5Specific risk associated with GE approaches; Risk of unintended genomic modifications; Safety risk involving unintended genomic modifications
Risk related to genomic integrity and insertional mutagenesis
Potential risk to be evaluated during biodistribution studies
Genomic integrity risk to be identified in safety assessments
Potential risk from DNA cleavage events including translocations; Risk associated with prolonged GE component activity
Related CFR Sections (4)
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR50.52§ 50.52 Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.
Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in which more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely tRead full regulation →
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
Related Warning Letters (1)
- 2025-03-25
Clinical Investigator
Americo F. Padilla, M.D.
See Also (8)
- Frequently Asked Questions — Developing Potential Cellular and Gene Therapy Products (Status: Draft)
- Institutional Review Boards Frequently Asked Questions: Guidance for Institutional Review Boards and Clinical Investigators (Status: Final)
- Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products: Guidance for Industry (Status: Final)
- Guidance for Human Somatic Cell Therapy and Gene Therapy: Guidance for Industry (Status: Final)
- Drug Master Files for Bulk Antibiotic Drug Substances: Guidance for Industry (Status: Final)
- INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information: Guidance for Industry (Status: Final)
- Pharmacogenomic Data Submissions; Examples of Voluntary Submissions or Submissions Required Under 21 CFR 312, 314, or 601 (Status: Final)
- Pharmacogenomic Data Submissions: Guidance for Industry (Status: Final)