101. FDA Regulations for the Protection of Human Subjects

Updated Oct. 4, 2019

With the additions and exceptions noted below, 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 policy 100 for an overview of and hyperlinks to FDA regulations, information sheets, and guidance.

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 subject in research unless the investigator has obtained the legally effective informed consent of the subject or the subject'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 of the following are true:

  • The human subject is confronted by a life-threatening situation necessitating the use of the test article.
  • Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject.
  • Time is not sufficient to obtain consent from the subject’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 subject.

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 subject, 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: At this time, 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 RI 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 DHHS regulations at 45 CFR 46.116 item (c) 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 (c)(2) 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 (a) and (b), 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 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 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.