What IRB Regulations Apply When? When HHS Regs (45 CFR 46) Apply vs. FDA Regs (21 CFR 50 and 56)

If your organization is planning research involving human participants, you may need to navigate IRB regulations. An IRB, or Institutional Review Board, is an independent 3rd party committee to which the federal government delegates authority on overseeing studies to ensure they protect participants' rights and welfare. First, you need to figure out whether or not your study even needs IRB approval. Then, it might be useful for you to have a general idea of which among the two sets of IRB regulations apply to your research and their similarities/differences, which is what this post is all about. The two key sets of regulations governing human subjects research include the HHS Common Rule (45 CFR 46) and the FDA's rules (21 CFR 50 and 21 CFR 56).

When Does the Common Rule (45 CFR 46) Apply?

The Common Rule, formally 45 CFR Part 46, establishes federal standards for protecting human subjects in research. It primarily applies to studies funded by specific U.S. government agencies, including the Department of Health and Human Services (HHS), the National Institutes of Health (NIH), the Department of Defense, and about 20 others that follow these guidelines.

45 CFR 46 covers a broad range of research activities, from social and behavioral studies to clinical trials, emphasizing informed consent, risk minimization, and data privacy. Even without federal funding, some organizations, journals, or partners may require adherence for ethical or credibility reasons. For the full details, refer to 45 CFR 46 on eCFR.

When Do the FDA Regulations (21 CFR 50 and 56) Apply?

FDA regulations come into play for research involving products regulated by the Food and Drug Administration. Specifically, 21 CFR Part 50 addresses informed consent protections, while 21 CFR Part 56 outlines IRB operations and responsibilities. These apply to "clinical investigations," defined as experiments on human subjects where the results may support an FDA marketing application (such as for drugs, devices, or biologics) or where study records may be held for inspection by the FDA (for example, as part of a product's design history file).

This is common in fields like pharmaceuticals, medical devices, and certain food or cosmetic testing, regardless of funding source. The focus is on ensuring participant safety in product-related studies. For more information, see 21 CFR 50 and 21 CFR 56 on eCFR.

Overlaps and Practical Differences: More Similar Than Different

Fortunately, the Common Rule and FDA regulations share core principles, such as obtaining informed consent, assessing risks versus benefits, and safeguarding privacy. If a study falls under both (e.g., federally funded research on an FDA-regulated device), a single IRB review can often address all requirements, provided it meets the stricter standards.

That said, there are some practical differences. The Common Rule is broader, applying to diverse research types like surveys or observational studies, and draws from ethical frameworks such as the Belmont Report, which stresses respect for persons, beneficence, and justice.

In contrast, FDA rules are more tailored to product evaluation, often requiring additional emphasis on safety monitoring, such as detailed adverse event reporting or product performance tracking. This is because the data may directly influence regulatory approvals or inspections. However, these additions typically build on the same foundation, making the overall process comparable. For guidance on preparing your submission under either framework, our unified Tempus IRB's Submission Readiness Checklist provides a practical overview.

Final Considerations: Determine Your Requirements Early

Identifying which regulations apply depends on your funding, research type, and whether FDA-regulated products are involved. Starting with this assessment can help avoid delays, especially for goals like publication or regulatory compliance. If uncertainties arise, professional consultation is recommended. At Tempus IRB, we assist organizations of all types with fast, transparent, and efficient IRB reviews tailored to these regulations. Schedule a call with us to discuss your needs, or sign up to submit a study!

This post is for informational purposes only and does not constitute legal advice.