105. FDA Regulations for IRB Review and Approval

Updated June 28, 2021

Part 56 of the Food and Drug Administration (FDA) regulations provide requirements for the composition, operation, and responsibilities of an IRB that reviews (a) FDA-regulated clinical investigations and (b) clinical investigations supporting applications for research or marketing permits for products regulated by the FDA. (For a list of FDA-regulated products see IRB policy for FDA regulations for the protection of human participants.)

FDA regulations mirror Department of Health and Human Services (DHHS) regulations for IRB requirements related to membership; functions and operations; review and approval of research; expedited review; institutional review; and review of cooperative research. The University IRB complies with these regulations. FDA exemptions from requirements for IRB review differ from DHHS exemptions. Otherwise, FDA regulations mirror DHHS regulations for IRB organization, functions and operations (e.g., review and approval), and record-keeping with additional FDA requirements listed below. See IRB policy on overview of FDA regulations, information sheets and guidance for a listing of relevant references.

Circumstances Requiring IRB Review under FDA Regulations

University and Affiliate investigators cannot initiate clinical investigations (i.e., experiments involving a test article and one or more human participants) requiring prior submission to FDA until the research has been reviewed and approved and remains subject to continuing review by an IRB meeting the requirements described herein. Unless the activity is exempt as described in the following section, prior submission to FDA is required for:

• Clinical Investigation involving an Investigational New Drug Application (per 21 CFR 312),
• Clinical Investigation involving an Investigational Device Exemption (per 21 CFR 812), or
• Activity involving a Humanitarian Use Device (per 21 CFR SUBPART H, 814.100-126).

FDA Exemptions from Requirement for Prior IRB Review and Approval

FDA regulations at §56.104 exempt the following categories of clinical investigations from the requirements for IRB review and approval, although the activities require an exempt determination or IRB notification.

1. Investigations that began before July 27, 1981, if the investigations (1) were subject to IRB review requirements under FDA regulations prior to that date and remain subject to review of an IRB that meets the FDA requirements in effect before July 27, 1981, or (2) were not otherwise subject to IRB review requirements under FDA regulations before July 27, 1981. (N/A, no research overseen by the University IRB meets either criterion.)
2. Emergency Use of an FDA-regulated test article (see Policy Manual Definitions) is exempted from requirements for prior IRB review and approval under specific conditions as long as the physician using the test article reports the emergency use to the University IRB within 5 working days and obtains prior IRB review and approval for any subsequent use. (See IRB policy for treatment, emergency, and expanded uses of investigational drugs, Humanitarian Use Devices, or treatment (compassionate) or emergency uses of investigational devices.)
3. Taste and food quality evaluations and consumer acceptance studies when (1) wholesome foods without additives are consumed; or (2) the food consumed contains a food ingredient at or below the level and for a use found to be safe, or an agricultural, chemical, or environmental contaminant at or below the level found to be safe by the FDA or approved by the EPA or the Food Safety and Inspection Service of the USDA. (Similar to DHHS Exempt Category 6; investigators should submit the Exempt Core Application Research with Participants form, available in IRBNet.)

FDA Waiver of IRB requirement

If applicable, University or Affiliate investigators must provide Research Integrity with written documentation of an FDA waiver of any of the requirements for IRB review for research otherwise covered by FDA regulations for IRBs.

Additional FDA Requirements for IRB Registration

In compliance with FDA regulations at §56.106, the University includes the types of FDA-regulated products involved in the protocols reviewed by the University IRB. Decisions to review new types of FDA-regulated products or discontinuation of review of clinical investigations (or disbanding of an IRB) would be reported within 30 days of the change or discontinuation (or disbanding).

FDA Requirements for IRB Membership, Functions, and Operations

The FDA requirements for IRB membership at §56.107 and IRB functions and operations at §56.108 mirror the DHHS requirements. (For details about how the University IRB applies these regulations, see these online Human Research Protection Program (HRPP) Policy Manual sections on IRB Membership, Meetings, and Records.)

FDA Requirements for IRB Review

FDA regulations for IRB review of research at §56.109 mirror those of DHHS (45 CFR 46.109). The University IRB complies with these regulations with the following caveats:

1. The University IRB recognizes the FDA exception from general requirements for informed consent for use of a test article in a life-threatening situation, as codified at 21 CFR 50.23, item (a).
2. The University IRB does not currently review or approve planned emergency research as specified under §50.24); the additional FDA requirements under §56.109, items (e) and (g) related to PI and Sponsor notifications for exceptions to informed consent do not apply.)

Additional FDA Requirements for Expedited Review

Use of expedited procedures for IRB review of FDA research (§ 56.110) is consistent with DHHS requirements for expedited review with the following additions:

Under expedited review Category 3, FDA (with agreement from DHHS) considers the following procedures to be noninvasive:

• Vaginal swabs that do not go beyond the cervical os;
• Rectal swabs that do not go beyond the rectum; and
• Nasal swabs that do not go beyond the nares.

The FDA may restrict, suspend, or terminate a University IRB's use of expedited review procedure when necessary to protect the rights or welfare of participants.

FDA Requirements for IRB Approval

The FDA criteria for IRB approval of research (at §56.111) mirror the DHHS criteria. In addition, when some or all the participants are children in research subject to FDA regulations, the IRB will confirm that the research complies with the FDA regulations at §50 Subpart D (which mirror the DHHS regulations described in the IRB policy for research involving children).

The University recognizes both DHHS and FDA regulations (§56.112) that specify research that has been approved by a University IRB may be subject to further appropriate review and approval or disapproval by officials of the University or Affiliate institutions. However, institutional officials may not approve the research if it has not been approved by the University IRB (unless the University IRB or Research Integrity authorized review by an external IRB).

Additional FDA Requirement for Reporting Suspension and Termination of IRB Approval

In compliance with §56.113, the University IRB will promptly report to the FDA any suspension or termination of IRB approval for FDA-regulated research. The report will include a statement of the reasons for the IRB's action.

Additional FDA Requirements for IRB Records

The University IRB complies with FDA requirements for IRB records at §56.115 (which mirror those of the Common Rule); and the additional requirement at §§(7)(b) for IRB records to be accessible for inspection and copying by FDA representatives at reasonable times and in a reasonable manner. The University IRB recognizes the authority of the FDA to refuse consideration of a clinical investigation if the IRB refuses to allow an inspection (per §§(7)(c)).

FDA Administrative Actions for Noncompliance

The University acknowledges the authority of the FDA as specified under §56.120 related to observation by an FDA investigator of apparent noncompliance with FDA regulations by a University IRB. Following notification by the FDA describing the noncompliance, the University agrees to respond to the letter within the FDA-specified time period. The University's response will describe corrective actions that will be taken by the IRB, the institution, or both to achieve compliance with FDA regulations.

The University acknowledges that the FDA may schedule a re-inspection to confirm the adequacy of correction actions; may place sanctions on FDA-regulated research conducted at the University or Affiliate institutions or reviewed and approved by a University IRB. The University acknowledges that when the noncompliance creates a significant threat to human research participants, the FDA will notify State and Federal regulatory agencies, and other parties with a direct interest in the matter. The University, as an institution within the Nevada System of Higher Education, accepts its primary responsibility for the operation of its IRB.

The University acknowledges that under §56.121-124, the FDA has the authority to disqualify the IRB or the University; publicly disclose information about the revocation; reinstate the IRB or University following FDA evaluation of proposed correction action; institute judicial proceedings (through the Department of Justice) or other appropriate regulatory action in addition to or in lieu of disqualification; and refer the matter to Federal, State, or local government agencies for appropriate action as determined by that governing body.