Lesson 11 · IRB and HRPP Administration: From Coordinator to CIP

11. The Criteria for IRB Approval: 45 CFR 46.111 Line by Line

55 min

After this lesson you can

  • Recite the criteria for approval in 45 CFR 46.111(a)(1) through (a)(8) and (b)
  • Explain how an IRB evaluates risk minimization and the reasonableness of risks relative to benefits
  • Apply the equitable selection criterion, including its attention to vulnerable populations
  • Connect criteria (4) and (5) to consent and criterion (7) to privacy and confidentiality
  • Identify the FDA parallels in 21 CFR 56.111 and the additional children's finding in 56.111(c)

Video coming soon

Scheduled for release on September 25, 2026.

IRB Criteria for Approval Explained: 45 CFR 46.111 and 56.111 walks through the findings every IRB must make before it can approve a study. This lesson reads each criterion, explains how reviewers apply it, and flags what does not count as a risk or a benefit.

5 Key Facts from This Lesson

  1. Every criterion in 45 CFR 46.111(a) must be satisfied, and the board cannot balance a weak finding against a strong one.
  2. Under 46.111(a)(2), the IRB should not consider the possible long-range effects of applying knowledge gained in the research, such as effects on public policy, as research risks.
  3. Payment to subjects is not a benefit to weigh against risk.
  4. Since the 2018 Requirements, the vulnerable populations list in 46.111(a)(3) names children, prisoners, individuals with impaired decision-making capacity, and economically or educationally disadvantaged persons, and no longer names pregnant women.
  5. FDA's parallel criteria are at 21 CFR 56.111, where paragraph (c) is an FDA-only provision pointing to the pediatric protections in 21 CFR 50 Subpart D.

Exam traps

The distinctions exam questions on this topic are most often built to test. Know them cold.

  • All eight criteria must be met; there is no balancing among them

  • Long-range public policy effects of the knowledge are excluded from the risk analysis

  • Payment to subjects is not a benefit to weigh against risk

  • The vulnerable populations list in (a)(3) no longer names pregnant women since the 2018 Requirements

  • 56.111(c) is FDA-only and points to 21 CFR 50 Subpart D

Practice quiz

  1. Question 1
    Under 45 CFR 46.111(a)(2), the IRB should NOT consider which of the following as a research risk?
  2. Question 2
    Which criterion requires that risks be minimized by using procedures already being performed on subjects for diagnostic or treatment purposes, when appropriate?
  3. Question 3
    Which populations are named in 46.111(a)(3) as raising special problems for equitable selection?
  4. Question 4
    An IRB may approve research only if:
  5. Question 5
    21 CFR 56.111(c) requires the IRB to make additional findings for clinical investigations involving:

Recap

  • All eight criteria and paragraph (b) must be satisfied; no balancing
  • (a)(1) risks minimized, (a)(2) risks reasonable, excluding clinical care risks and long-range effects; payment is not a benefit
  • (a)(3) equitable selection with the 2018 list of vulnerable populations
  • (a)(4) and (a)(5) consent sought and documented; (a)(6) data monitoring; (a)(7) privacy and confidentiality; (a)(8) broad consent; (b) additional safeguards
  • 56.111 parallels (a)(1) through (a)(7) and (b), has no (a)(8), and adds (c) for children

Coming next

Lesson 12, the elements of informed consent, key information, broad consent, and waivers.

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This course is for educational purposes only and is not legal, regulatory, or compliance advice. Regulations and guidance change, so confirm every requirement against the current eCFR text, OHRP and FDA guidance, and your institution's IRB policies before relying on it. CIP® is a registered certification mark of Public Responsibility in Medicine and Research (PRIM&R). This course is produced independently by Subthesis and is not affiliated with, endorsed by, or reviewed by PRIM&R or the CIP Council. The instructor is not a Certified IRB Professional. Completing this course does not confer CIP certification, satisfy CIP eligibility requirements, or count as CIP recertification continuing education.