101. FDA Regulations for the Protection of Human Research Participants

Updated June 28, 2021

With the additions and exceptions noted below, the Food and Drug Administration (FDA) regulations for the Protection of Human Subjects under the Common Rule (available at 21 CFR 50) apply to the following:

  • Clinical investigations regulated by the FDA under sections 505(i) and 520(g) of the Federal Food, Drug, and Cosmetic Act, and
  • Clinical investigations which support applications for research or marketing permits for products regulated by the FDA.

Products regulated by the FDA include:

  • foods,
  • dietary supplements that bear a nutrient content claim or a health claim,
  • infant formulas,
  • food and color additives,
  • drugs for human use,
  • medical devices for human use,
  • biological products for human use, and
  • electronic products.

See IRB policy on overview of FDA regulations, information sheets and guidance for a listing of relevant references.

Participant Recruitment under FDA Regulations

The IRB will review recruitment materials to ensure that advertisements do not:

  • Make claims, either explicitly or implicitly, about the drug, biologic, or device under investigation that are inconsistent with FDA labeling.
  • Use terms, such as “new treatment,” “new medication,” or “new drug,” without explaining that the test article is investigational.
  • Allow compensation for participation in a trial offered by a sponsor to include a coupon good for a discount on the purchase price of the product once it has been approved for marketing.

Informed Consent under FDA Regulations

General Requirements for Informed Consent

In compliance with general requirements for informed consent under the Common Rule (45 CFR 46.116 and 21 CFR 50.20 and §50.25), University and Affiliate investigators may not involve a human being as a participant in research unless the investigator has obtained the legally effective informed consent of the participant or the participant’s legally authorized representative. However, the FDA and the University IRB recognize that obtaining informed consent may not be feasible under all circumstances and comply with the three FDA exceptions from general consent requirements (21 CFR 50.23, items (a), (b) and (c)).

FDA Exception from General Consent Requirements: Item (a)

The FDA exception for general consent requirements found under §50.23 item (a) applies if before use of the test article, both the investigator and a physician who is not otherwise participating in the clinical investigation certify (in writing) all the following are true:

  • The human participant is confronted by a life-threatening situation necessitating the use of the test article.
  • Informed consent cannot be obtained from the participant because of an inability to communicate with, or obtain legally effective consent from, the participant.
  • Time is not sufficient to obtain consent from the participant’s legal representative.
  • No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the life of the participant.

FDA Exception from General Consent Requirements: Item (b)

Under §50.23 item (b) applies if it is the investigator's opinion that immediate use of the test article is required to preserve the life of the participant, and time is not sufficient to obtain the determination of an independent physician in advance of using the test article (as described above), the article may be used. However, within 5 working days after the use of the article, the determinations of the clinical investigator must be reviewed and evaluated in writing by a physician who is not participating in the clinical investigation.

Investigator Requirements for Notifying the IRB of FDA Exceptions from Informed Consent Requirements

Per §50.23, item (c), University and Affiliate investigators must submit the required documentation for informed consent exceptions under (a) and (b) to the IRB within 5 working days after the use of the test article.

Presidential Exceptions for Prior Informed Consent Requirements

Per §50.23, item (d), The President may waive the prior consent requirement for the administration of an investigational new drug to a member of the armed forces in connection with the member's participation in a particular military operation.

NOTE: To date, the University IRB has never received such a request. If this situation should occur at a University or Affiliate site, the IRB will refer to §50.23(d) to evaluate the request with consideration for the multiple requirements applicable to a Presidential exception to informed consent.

FDA Exception to Consent Requirements for Planned Emergency Research

FDA regulations allow exceptions to consent requirements for planned emergency research under specific conditions (for details, see §50.24).

IMPORTANT NOTE: Currently, neither the University nor its Affiliate sites actively conduct or manage such research; therefore, the University does not have policies for planned emergency research. Investigators interested in conducting planned emergency research must contact Research Integrity to discuss the possibility of engaging in this type of research. As warranted, the IRB will develop and publish policy for such research.

Obtaining IRB Approval to Waive or Alter Informed Consent for Activities Preparatory to Research

The Department of Health and Human Services (DHHS) regulations at 45 CFR 46.116 that allow the IRB to waive or alter the requirements for informed do not apply to FDA-regulated research. However, the University IRB considers minimal risk activities that occur prior to a participant’s enrollment in FDA-regulated research (i.e., activities preparatory to research) to be eligible for a DHHS waiver/alteration of informed consent when the conditions specified under item (f)(3)(ii) are met. Applicable activities include review of medical or other private records to identify individuals who are eligible for a research project. Investigators must complete the consent waivers researcher form (available in IRBNet) to secure IRB approval to waive or alter the requirements for informed consent for such activities.

FDA Requirements/Additions to Elements of Informed Consent

Requirements for researchers to provide basic and additional elements for informed consent for FDA-regulated research found at 21 CFR 50.25 mirror the DHHS requirements at 45 CFR 46.116, items (b) and (c), with the following two notable FDA additions (per items (a)(5), and (c)):

  • Consent documents must note the possibility that the Food and Drug Administration may inspect study records.
  • Researchers conducting applicable clinical trials, as defined in 42 U.S.C. 282(j)(1)(A), must include the following FDA-required statement in consent documents:

“A description of this clinical trial will be available on http://clinicaltrials.gov/, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

FDA regulations further specify that FDA informed consent requirements neither preempt applicable Federal, State, and local laws requiring additional information to be disclosed for legally effective informed consent; nor limit the authority of a physician to provide emergency medical care when provided as she/he/they is permitted under applicable federal, state, and local law.

Investigators who do not plan to provide the basic and additional elements for informed consent must request IRB approval for an alteration of informed consent.

FDA Requirements for Documentation of Informed Consent

FDA requirements for researchers to document signed consent for all research participants at 21 CFR 50.27 mirror the DHHS requirements at 45 CFR 46.117 with the exceptions described at 21 CFR 56.109 items (c)(1) or (2). Specifically, the IRB may waive the requirement for documentation of informed consent for minimal risk research that does not require signed consent outside of the research context and for emergency research.

FDA regulations (§50.27, item (b)(2)) reference use of a short form written consent document. As noted in the IRB policy for informed consent requirements, a short form written consent document may be used when a prospective participant or legally authorized representative cannot read the IRB-approved consent form. (For requirements, see the online HRPP Policy Manual for short form written consent).

FDA Requirements for Waivers and Alterations of Informed Consent

Currently, FDA’s regulations governing the protection of human participants (21 CFR parts 50 and 56) allow exception from the general requirements for informed consent only in life-threatening situations when certain conditions are met (21 CFR 50.23) or when the requirements for emergency research are met (21 CFR 50.24). The July 2017 Guidance for Sponsors, Investigators, and IRBs: IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More than Minimal Risk to Human Subjects states:

Waiver of informed consent for certain FDA-regulated minimal risk clinical investigations will facilitate investigators’ ability to conduct studies that may contribute substantially to the development of products to diagnose or treat diseases or conditions, or address unmet medical needs. In light of the Cures Act amendment to the FD&C Act described above, FDA intends to revise its informed consent regulations to add this waiver or alteration under appropriate human subject protection safeguards to the two existing exceptions from informed consent (i.e., in life-threatening situations and for emergency research). However, until FDA promulgates these regulations, we do not intend to object to an IRB approving a consent procedure that does not include, or that alters, some or all the elements of informed consent set forth in 21 CFR 50.25, or waiving the requirements to obtain informed consent when the IRB finds and documents that:

  1. The clinical investigation involves no more than minimal risk (as defined in 21 CFR 50.3(k) or 56.102(i)) to the subjects;
  2. The waiver or alteration will not adversely affect the rights and welfare of the subjects;
  3. The clinical investigation could not practicably be carried out without the waiver or alteration; and
  4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

FDA does not intend to object to a sponsor initiating, or an investigator conducting, a minimal risk clinical investigation for which an IRB waives or alters the informed consent requirements as described above. FDA intends to withdraw this guidance after we promulgate regulations to permit a waiver or alteration of informed consent under appropriate human subject protection safeguards consistent with section 3024 of the Cures Act.

Waiver or Alteration of the Consent Process – Obtaining Consent Not Practicable

  • The clinical investigation involves no more than minimal risk to the participants.
  • The clinical investigation cannot practicably be carried out without the waiver or alteration.
  • The waiver or alteration will not adversely affect the rights and welfare of the participants.
  • When appropriate, the participants will be provided with additional pertinent information after participation.

Waiver Requirements for Planned Emergency Research

An IRB may approve planned research in an emergency setting without the informed consent of the participants or their legally authorized representatives in a limited class of emergency situations when the following criteria are met and documented:

  • Potential subjects are in a life-threatening situation, and
  • available treatments are unproven or unsatisfactory and
  • collection of scientific data is required to determine the safety and effectiveness of the experimental intervention
  • Obtaining informed consent is not feasible because:
    • the potential subject is not able to consent due to his/her medical condition
    • the intervention must be administered before consent from the potential subject’s authorized representative is feasible and
    • there is no reasonable way to prospectively identify potential eligible subjects
  • Participation in the research study holds out the prospect of direct benefit to the subjects because:
    • the subjects are facing a life-threatening situation
    • appropriate pre-clinical and prior clinical research studies support the potential for direct benefit and
    • the risks associated with the research are reasonable relative to the risks of the subjects’ condition and the risk/benefit ratio of standard therapy for the condition
  • The research could not be practicably carried out without the waiver.

FDA Additional Safeguards for Children in Clinical Investigations

FDA regulations (at 21 CFR 50, Subpart D) for research involving children mirror the requirements in Subpart D of the DHHS regulations but use “clinical investigation” instead of “research.” See the IRB policy manual for research involving children for information about categories of research; requirements for parental consent and child assent; and regulations for research involving children who are wards of the State or other agency, institution or entity.