Description
This guidance is intended to assist clinical investigators, sponsors, sponsor-investigators, and institutional review boards (IRBs) in determining whether research studies involving human subjects must be conducted under an investigational new drug application (IND), as described in title 21 of the Code of Federal Regulations, part 312 (21 CFR part 312) (the IND regulations). This guidance describes when an IND is required, specific situations in which an IND is not required, and a range of issues that, in FDA’s experience, have been the source of confusion or misperceptions about the application of the IND regulations.3 This guidance addresses only whether an IND is needed. If your study also involves the use of a device, you should determine whether such use is subject to 21 CFR part 812 (the IDE regulations).
Scope & Applicability
Product Classes
10Research involving marketed drug products exempt from IND
Positron emission tomography drugs
The primary product category covered by the guidance; Essential food product that is the sole source of nutrition for many infants.
Part of the definition of critical food
Food marketed for general consumption, distinct from dietary supplements.; Comparison point for intake levels
Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
Subject to sampling requirements under 702(b).; Cosmetic means articles intended to be rubbed, poured, sprinkled, or sprayed on the human body
Defined under section 201(i)
Carotenoid Vitamin A Precursors and Analogs in Foods
Category of products covered in the table of contents; Covered by allergen labeling requirements; Guidance on declaring major food allergens for dietary supplements.
Stakeholders
7Individuals responsible for monitoring and reporting protocol deviations
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
Entity responsible for submitting applications under section 524B
committee that approves human research using radioactive drugs
Assist sponsors in the nonclinical evaluation
Individual who both initiates and conducts an investigation.
Institutional Review Board providing study approvals
Regulatory Context
Attributes
2Status of a drug product in the United States
primary characteristic of food
Identified Hazards
Hazards
2Assessment of toxicity required in a 351(k) BLA
Safety concern if product heterogeneity is inconsistent
Related CFR Sections (8)
- 21CFR312.120§ 312.120 Foreign clinical studies not conducted under an IND.
(a) Acceptance of studies.Read full regulation →
- 21CFR101.81§ 101.81 Health claims: Soluble fiber from certain foods and risk of coronary heart disease (CHD).
(a) Relationship between diets that are low in saturated fat and cholesterol and that include soluble fiber from certain foods and the risk of CHD.Read full regulation →
- 21CFR312.22§ 312.22 General principles of the IND submission.
(a) FDA's primary objectives in reviewing an IND are, in all phases of the investigation, to assure the safety and rights of subjects, and, in Phase 2 and 3, to help assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of the drug's effectiveness and safeRead full regulation →
- 21CFR312.3§ 312.3 Definitions and interpretations.
(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part:Read full regulation →
- 21CFR312.2§ 312.2 Applicability.
(a) Applicability. Except as provided in this section, this part applies to all clinical investigations of products that are subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to the licensing provisions of the Public Health Service Act (58 Stat. 632, as amended ( 42 U.S.C. 201 etRead full regulation →
- 21CFR320.31§ 320.31 Applicability of requirements regarding an “Investigational New Drug Application.”
(a) Any person planning to conduct an in vivo bioavailability or bioequivalence study in humans shall submit an “Investigational New Drug Application” (IND) if:Read full regulation →
- 21CFR314.108§ 314.108 New drug product exclusivity.
(a) Definitions. The definitions in § 314.3 and the following definitions of terms apply to this section:Read full regulation →
- 21CFR361.1§ 361.1 Radioactive drugs for certain research uses.
(a) Radioactive drugs (as defined in § 310.3(n) of this chapter ) are generally recognized as safe and effective when administered, under the conditions set forth in paragraph (b) of this section, to human research subjects during the course of a research project intended to obtain basic informationRead full regulation →
Related Warning Letters (10)
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-11-18
Sponsor/Investigator
Verdure Sciences, Inc.
- 2025-09-30
Clinical Investigator (Sponsor)
Pamela K. Den Besten, DDS, MS
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-07-01
Clinical Investigator
Peter Michael, M.D.
- 2025-06-10
Clinical Investigator (Sponsor)
American Behavioral Research Institute, LLC
- 2025-06-03
Bioresearch Monitoring Program
Amy Lightner, MD
See Also (8)
- Expedited Programs for Regenerative Medicine Therapies for Serious Conditions: Draft Guidance for Industry (Status: Draft)
- Clinical Development and Labeling of Anti-Infective Drug Products (Status: Final)
- Guidance for Industry: Exports Under the FDA Export Reform and Enhancement Act of 1996 : Guidance for Industry (Status: Final)
- Frequently Asked Questions – Statement of Investigator (Form FDA 1572): Guidance for Sponsors, Clinical Investigators, and IRBs (Status: Final)
- Influenza: Developing Drugs for Treatment and/or Prophylaxis (Status: Final)
- General Principles for the Development of Vaccines to Protect Against Global Infectious Diseases: Guidance for Industry (Status: Final)
- Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (Status: Final)
- Considerations for Generating Clinical Evidence from Oncology Multiregional Clinical Development Programs (Status: Draft)