Description
This guidance is intended to assist institutional review boards (IRBs) in carrying out their continuing review responsibility under 21 CFR 56.108(a) and 56.109(f) by providing recommendations regarding the criteria, process, and frequency of continuing review to assure the protection of the rights and welfare of human subjects enrolled in clinical investigations. This guidance should also help clinical investigators and sponsors better understand their responsibilities related to continuing review. This document supersedes the Information Sheet, Continuing Review After Study Approval (September 1998, Office of Health Affairs, FDA). To enhance human subject protection and reduce regulatory burden, the Department of Health and Human Services (HHS), Office for Human Research Protections (OHRP) and FDA have been actively working to harmonize the agencies’ regulatory requirements and guidance for human subject research. This guidance document was developed as a part of these efforts.
Scope & Applicability
Product Classes
5Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
FDA intends to assess device cybersecurity based on a number of factors; demonstrate or maintain its safety and effectiveness; ensuring cybersecurity has become essential to FDA’s ability to protect the public health; Cyber-resiliency capabilities for medical devices
Example of research intervention that may hold prospect of direct benefit during a lapse.
Defined in section 201(h) of the FD&C Act; Instrument or apparatus which does not achieve primary purpose through chemical action; Product classification based on primary intended purpose and chemical action
Product of biological origin applicable to prevention or treatment of disease.
Stakeholders
7Governs top dose in clinical studies
individual who may conduct expedited reviews
Body responsible for reviewing risk determinations.
Entity to which obligations may be transferred
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
Entity responsible for submitting applications under section 524B
Institutional Review Board providing study approvals
Regulatory Context
Attributes
3Risk level for exception from informed consent
Property of a device that may be changed via established protocols
The date on which IRB approval becomes active
Identified Hazards
Hazards
4Changes initiated without IRB approval to eliminate hazards
Grounds for the IRB to suspend or terminate approval of a clinical investigation.
Potential for harm to participants which must be minimized and reasonable
Potential for harm that must be minimized and balanced against benefits
Related CFR Sections (12)
- 21CFR56.110§ 56.110 Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research.
(a) The Food and Drug Administration has established, and published in the Federal Register, a list of categories of research that may be reviewed by the IRB through an expedited review procedure. The list will be amended, as appropriate, through periodic republication in the Federal Register.Read full regulation →
- 21CFR56.108§ 56.108 IRB functions and operations.
In order to fulfill the requirements of these regulations, each IRB shall:Read full regulation →
- 21CFR812.110§ 812.110 Specific responsibilities of investigators.
(a) Awaiting approval. An investigator may determine whether potential subjects would be interested in participating in an investigation, but shall not request the written informed consent of any subject to participate, and shall not allow any subject to participate before obtaining IRB and FDA apprRead full regulation →
- 21CFR312.53§ 312.53 Selecting investigators and monitors.
(a) Selecting investigators. A sponsor shall select only investigators qualified by training and experience as appropriate experts to investigate the drug.Read full regulation →
- 21CFR56.113§ 56.113 Suspension or termination of IRB approval of research.
An IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for Read full regulation →
- 21CFR56.115§ 56.115 IRB records.
(a) An institution, or where appropriate an IRB, shall prepare and maintain adequate documentation of IRB activities, including the following:Read full regulation →
- 21CFR56.109§ 56.109 IRB review of research.
(a) An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by these regulations.Read full regulation →
- 21CFR56.111§ 56.111 Criteria for IRB approval of research.
(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:Read full regulation →
- 21CFR56.114§ 56.114 Cooperative research.
In complying with these regulations, institutions involved in multi-institutional studies may use joint review, reliance upon the review of another qualified IRB, or similar arrangements aimed at avoidance of duplication of effort.Read full regulation →
- 21CFR812.40§ 812.40 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators and providing them with the information they need to conduct the investigation properly, ensuring proper monitoring of the investigation, ensuring that IRB review and approval are obtained, submitting an IDE application to FDA, and ensurRead full regulation →
- 21CFR312.33§ 312.33 Annual reports.
A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes:Read full regulation →
- 21CFR50.25§ 50.25 Elements of informed consent.
(a) Basic elements of informed consent. In seeking informed consent, the following information shall be provided to each subject:Read 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)
- Informed Consent: Guidance for IRBs, Clinical Investigators, and Sponsors (Status: Final)
- Institutional Review Board (IRB) Written Procedures: Guidance for Institutions and IRBs (Status: Final)
- Adverse Event Reporting to IRBs — Improving Human Subject Protection: Guidance for Clinical Investigators, Sponsors, and IRBs (Status: Final)
- CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
- Considerations When Transferring Clinical Investigation Oversight to Another IRB: Guidance for IRBs, Clinical Investigators, and Sponsors (Status: Final)
- Minutes of Institutional Review Board (IRB) Meetings: Guidance for Institutions and IRBs (Status: Final)
- Key Information and Facilitating Understanding in Informed Consent Guidance for Sponsors, Investigators, and Institutional Review Boards (Status: Draft)
- Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval: Draft Guidance for Industry (Status: Draft)