100. Overview of FDA Regulations, Information Sheets and Guidance

Updated July 26, 2021

The Food and Drug Administration (FDA) is a Health and Human Services (HHS) agency that regulates clinical investigations of products under its jurisdiction including drugs, biological products, and medical devices.

FDA regulations are published in title 21 of the CFR. The following FDA human research regulations apply to the IRB and to University and Affiliate researchers conducting clinical trials, and research involving investigational drugs and devices:

21 CFR 50 Protection of Human Subjects (i.e., The Common Rule)
21 CFR 56 Institutional Review Boards
21 CFR 312 Investigational New Drug Application (IND)
21 CFR 812 Investigational Device Exemptions (IDE)

NOTE: The University IRB follows the International Conference on Harmonization - Good Clinical Practice E6 guideline ICH‐GCP (E6) only to the extent required by DHHS and FDA regulations, information sheets and guidance documents; and, when applicable, federal, state, or local laws or regulations international laws, regulations, and guidelines.

When research involving investigational or unlicensed test articles is conducted outside of the U.S., the requirements in country law should be followed.

The University IRB applies the following additional FDA regulations when applicable:

21 CFR 11 Electronic Records; Electronic Signatures
21 CFR 54 Financial Disclosure by Clinical Investigators
21 CFR 210 Current Good Manufacturing Practice in Manufacturing Processing Packing or Holding of Drugs; General
21 CFR 211 Current Good Manufacturing Practice for Finished Pharmaceuticals
21 CFR 314 Applications for FDA Approval to Market a New Drug
21 CFR 320 Bioavailability and Bioequivalence Requirements
21 CFR 330 Over-the-Counter (OTC) Human Drugs Which Are Generally Recognized as Safe and Effective and Not Misbranded
21 CFR 601 Licensing [Biologics]
21 CFR 807 Establishment Registration and Device Listing for Manufacturers and Initial Importers of Devices
21 CFR 814 Premarket Approval of Medical Devices
21 CFR 820 Quality System Regulation
21 CFR 860 Medical Device Classification Procedures

Research Integrity and the University IRB rely on the following FDA Information Sheets and guidance documents when relevant:

FDA Information Sheet: A Guide to Informed Consent
FDA Information Sheet: Non-Local IRB Review
FDA Information Sheet: Payment to Research Subjects
FDA Information Sheet: Recruiting Study Subjects
Information Sheet Guidance for IRBs and Clinical Investigators: Emergency Use of an Investigational Drug or Biologic
Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors: Frequently Asked Questions About Medical Devices
Institutional Review Boards Frequently Asked Questions - Information Sheet: Information Sheet - Guidance for Institutional Review Boards and Clinical Investigators Information Sheet (includes chapters for IRB Organization, IRB Membership, IRB Procedures, IRB Records, Informed Consent Process, Informed consent Document Content, Clinical Investigations, and General Questions)
Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical Investigators
Guidance for Clinical Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs - Improving Human Subject Protection
Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs) - Determining Whether Human Research Studies Can Be Conducted Without an IND
Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing Review After Clinical Investigation Approval
Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed
Guidance for Sponsors, Clinical Investigators, and IRBs: Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials

FDA offers Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception From Informed Consent Requirements for Emergency Research which clarifies the regulations at 21 CFR 50.24 and the conforming amendments contained in 21 CFR Parts 56, 312, 314, 601, 812, and 814 provide a narrow exception to the requirement that the investigator obtain informed consent from each participant, or the participant’s legally authorized representative, prior to enrollment in emergency research. The regulations also provide additional protections for participants enrolled in these studies. For example, the regulations require consultation with representatives of and public disclosure to the communities in which the clinical investigation will be conducted and from which the participants will be drawn, prior to initiation of the clinical investigation. They also require public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study. As well, the regulations require that an independent data monitoring committee exercises oversight of the clinical investigation. This exception is currently not available to University or Affiliate Researchers. Individuals proposing to conduct planned emergency research are to contact Research Integrity to discuss the proposed research and allow Research Integrity time to prepare a policy, researcher form, and review worksheet.

IRB Review of FDA Research

The IRB requires additional information for FDA research conducted under an IND or IDE to verify that investigators address IRB-relevant elements specific to FDA regulations.
Research conducted under IND or IDE is reviewed at convened IRB meetings, except for continuing reviews that meet the criteria for expedited review under Categories 8(a), 8(b), or 8(c) or reviews of minor modifications (see Policy Manual Definitions) to previously approved research.
In presenting the protocol to the IRB, the primary reviewer will address the additional FDA regulatory requirements.
As warranted, the IRB will request policies from Affiliate sites to assess mechanisms for control of FDA-regulated test articles.

The University IRB ensures clinicians comply with FDA regulations when using investigational articles outside of the research setting. For information about the specific uses, see IRB policy for:

treatment or emergency uses of investigational drug or biologic, and
emergency, treatment, and compassionate uses of investigational devices.

The IRB also oversees situations in which clinicians and investigators use "Humanitarian Use Devices" (i.e., medical devices intended to benefit patients with diseases that affect fewer than 8,000 persons in the US annually).

NOTE: FDA and DHHS human research protection regulations differ. For research subject to review under FDA and DHHS human research regulations, both sets of regulations apply and the requirements for both sets of regulations must be met.