Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations: Draft Guidance for Industry

Description

This guidance provides recommendations to sponsors who are planning clinical trials of cell and gene therapy (CGT) products intended for use in a disease or condition that affects a small population—generally one that meets the definition of a rare disease or condition under section 526(a)(2) of the FD&C Act (21 U.S.C. 360bb(a)(2)).  It describes FDA requirements and provides considerations for the use of various clinical trial designs and endpoints to generate clinical evidence to support product licensure.  This guidance expands on principles described in FDA’s existing guidance documents related to this topic, ,   by providing additional recommendations for the planning, design, conduct, and analysis of cell and gene therapy trials to facilitate FDA’s assessment of product effectiveness.

Scope & Applicability

Regulatory Context

• 21CFR50.54§ 50.54 Clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.

  If an IRB does not believe that a clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter and involving children as subjects meets the requirements of § 50.51 , § 50.52 , or § 50.53 , the clinical investigation may proceed only if:Read full regulation →

• 21CFR50.53§ 50.53 Clinical investigations involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects' disorder or condition.

  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 does not hold out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is 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 →

• 21CFR50.51§ 50.51 Clinical investigations not involving greater than minimal risk.

  Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in which no greater than minimal risk to children is presented may involve children as subjects only if the IRB finds that:Read full regulation →

• 21CFR314.126§ 314.126 Adequate and well-controlled studies.

  (a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →

• 21CFR600.3§ 600.3 Definitions.

  As used in this subchapter:Read full regulation →

• Clinical Investigator

  Shirish M. Gadgeel, M.D.

  2025-09-09

• Clinical Investigator

  Mark J. Savant, M.D

  2025-07-15

• Bioresearch Monitoring Program/Institutional Review Board (IRB)

  United Health Products, Inc.

  2025-05-20

• Clinical Investigator

  Americo F. Padilla, M.D.

  2025-03-25

• Institutional Review Board (IRB)

  Armstrong County Memorial Hospital

  2024-11-05

• Clinical Investigator

  Namita A. Goyal, M.D.

  2024-10-22

• Institutional Review Board (IRB)

  Louisiana State University Health Science Center IRB

  2024-10-08

• Bioresearch Monitoring Program/IRB

  Massachusetts Institute of Technology MIT

  2024-07-16

• Institutional Review Board (IRB)

  New York State Psychiatric Institute IRB

  2024-03-26

• Investigational Device Exemptions (Clinical Investigator)

  Mobeen Mazhar, M.D.

  2023-06-06

• CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
• Process for Handling Referrals to FDA Under 21 CFR 50.54 - Additional Safeguards for Children in Clinical Investigations: Guidance for Clinical Investigators, Institutional Review Boards and Sponsors (Status: Final)
• Exception from Informed Consent Requirements for Emergency Research: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors (Status: Final)
• Premarket Assessment of Pediatric Medical Devices: Guidance for Industry and FDA Staff (Status: Final)
• Minutes of Institutional Review Board (IRB) Meetings: Guidance for Institutions and IRBs (Status: Final)
• General Clinical Pharmacology Considerations for Pediatric Studies of Drugs, Including Biological Products (Status: Draft)
• Ethical Considerations for Clinical Investigations of Medical Products Involving Children: Draft Guidance for Industry, Sponsors, and IRBs (Status: Draft)
• Human Gene Therapy for Neurodegenerative Diseases: Guidance for Industry (Status: Final)