Description
This guidance is intended to clarify what preclinical and clinical approaches, as well as chemistry, manufacturing, and controls information, should be considered when planning exploratory studies in humans, including studies of closely related drugs or therapeutic biological products, under an investigational new drug (IND) application (21 CFR 312). Existing regulations allow a great deal of flexibility in the amount of data that needs to be submitted with an IND application, depending on the goals of the proposed investigation, the specific human testing proposed, and the expected risks. The Agency believes that sponsors have not taken full advantage of that flexibility and often provide more supporting information in INDs than is required by regulations. This guidance is intended to clarify what manufacturing controls, preclinical testing, and clinical approaches can be considered when planning limited, early exploratory IND studies in humans.
Scope & Applicability
Product Classes
5Category of products subject to Subpart E regulations.
EFD evaluation typically in two species for small molecules
Products for which batch/lot information is particularly important
Mass balance studies should be conducted for all new molecular entities
Trials evaluating biologics for CRSwNP
Stakeholders
4Entity responsible for submitting applications under section 524B
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
Governs top dose in clinical studies
committee that approves human research using radioactive drugs
Regulatory Context
Attributes
3requirement for ophthalmic or parenteral products
AUC or Cmin may correlate with efficacy
state the basis for the margin of safety for the NDI; Calculated by dividing the NOAEL by the estimated daily intake (EDI).; A measure of how close the estimated daily intake is to the NOAEL
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 →
- 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 →
- 21CFR330.1§ 330.1 General conditions for general recognition as safe, effective and not misbranded.
An over-the-counter (OTC) drug listed in this subchapter is generally recognized as safe and effective and is not misbranded if it meets each of the conditions contained in this part and each of the conditions contained in any applicable monograph. Any product which fails to conform to each of the cRead 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.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-07-01
Clinical Investigator
Peter Michael, M.D.
See Also (8)
- Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the FD&C Act (Status: Final)
- Enhancing Participation in Clinical Trials — Eligibility Criteria, Enrollment Practices, and Trial Designs: Guidance for Industry (Status: Final)
- Study of Sex Differences in the Clinical Evaluation of Medical Products (Status: Draft)
- CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
- Preparation of Investigational New Drug Products (Human and Animal): Guidance for Industry (Status: Final)
- Formatting, Assembling and Submitting New Drug and Antibiotic Applications* (Status: Final)
- Nuclear Pharmacy Guideline Criteria for Determining When to Register as a Drug Establishment (Status: Final)
- Guidance for Industry: Exports Under the FDA Export Reform and Enhancement Act of 1996 : Guidance for Industry (Status: Final)