Description
The Center for Biologics Evaluation and Research (CBER)/Office of Cellular, Tissue, and Gene Therapies (OCTGT) is issuing this guidance to assist sponsors and investigators in designing early-phase clinical trials for cellular therapy (CT) and gene therapy (GT) products. CT and GT products will be referred to collectively as CGT products. This guidance provides OCTGT’s current recommendations regarding clinical trials in which the primary objectives are the initial assessments of safety, tolerability, or feasibility of administration of investigational products. Such trials include most Phase 1 trials, including the initial introduction of an investigational new drug into humans, and some Phase 2 trials of CGT products.
Scope & Applicability
Product Classes
9Guidance focuses on innovative designs for clinical trials of these products.; Innovative designs for clinical trials of CGT products.
Includes genetically modified cells
Specific category for CMC guidance
General term for gene therapy products discussed in the text
Cell therapy product derived from cord blood
CGT products that may be used as therapeutic vaccines.
Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271
Products in which a gene is introduced into cells ex vivo
Identifying subjects whose tumors express a specific target antigen
Stakeholders
6Entity responsible for submitting applications under section 524B
Target population for drug development and disease definition
Safety oversight body for interpreting adverse events; Safety oversight body for study design
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Individuals who do not have the disease or condition of interest
Additional safeguards for children in clinical investigations
Regulatory Context
Attributes
5Assessment required for therapeutic protein products.
Basis for dosing many GT products
can differ from lot to lot
regulatory threshold for involving children in clinical investigations
Percentage of living cells measured after exposure to extracts; Measured as a percentage of the media control
Identified Hazards
Hazards
1Endpoint used to calculate TD50
Related CFR Sections (3)
- 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 →
- 21CFR312.21§ 312.21 Phases of an investigation.
An IND may be submitted for one or more phases of an investigation. The clinical investigation of a previously untested drug is generally divided into three phases. Although in general the phases are conducted sequentially, they may overlap. These three phases of an investigation are a follows: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 →
Related Warning Letters (10)
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-16
Deviations/CFR/Regulations for Human Cells, Tissues & Cellular Products (HCT/Ps)
Green Valley Fertility Partners
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
BioXtek LLC
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Lux Therapeutics LLC dba Ponya Therapeutics LLC
- 2025-11-18
Sponsor/Investigator
Verdure Sciences, Inc.
- 2025-10-07
CGMP/Deviations/Biologics License Application (BLA)
New Life Medical Services, LLC
- 2025-09-30
Clinical Investigator (Sponsor)
Pamela K. Den Besten, DDS, MS
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, 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)