Human Subject Protection Regulations: Differences Between HHS’ & FDA’s Clinical Trial Rules

October 22, 2018

On Friday, October 12th, FDA issued a guidance document entitled “Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical Investigations.”  The document aims to help sponsors, investigators, and institutional review boards (IRBs) comply with the different human subject protection regulations of each agency, and focuses on informed consent, expedited review procedures, and IRB continuing review.


What is the Common Rule?

The Federal Policy For the Protection of Human Research Subjects (or “the Common Rule”) from the Department of Health and Human Services (HHS) lists a number of requirements that are intended to protect the human subjects involved in research that is conducted or supported by HHS.  The Common Rule promotes uniformity, understanding, and compliance with human subject protections and creates a uniform body of regulations across the federal departments and agencies.

“FDA’s regulations on human subject protection (21 CFR part 50) and Institutional Review Boards (IRBs; 21 CFR part 56) help to ensure that the rights, safety, and welfare of human subjects participating in FDA-regulated clinical investigations are protected.”  In 1991, FDA amended its regulations to conform with the Common Rule (with a few exceptions due to differences in FDA’s mission or statute).

FDA, HHS, & The 21st Century Cures Act

On December 13, 2016, the 21st Century Cures Act was signed into law.  “Section 3023 directs the Secretary of HHS, to the extent practicable and consistent with other statutory provisions, to harmonize differences between the HHS’ human subject regulations and FDA’s human subject regulations.”

On January 19, 2017, HHS and a number of other federal departments published a final rule that revised the Common Rule.  The revisions to the Common Rule (“2018 Requirements”) created differences between FDA & HHS human subject regulations.

FDA’s Human Subject Protection Regulations

The change in regulations will require many studies to comply with both HHS’ and FDA’s human subject regulations.  As such, it is important for sponsors, investigators, and IRBs to be familiar with these regulations.  FDA plans to blend its regulations with the 2018 Requirements as much as possible to achieve consistency between the two sets of regulations; however, the Agency also notes that it recognizes the potential for confusion until that is accomplished.  The FDA’s guidance document is intended to minimize that confusion by clarifying “the impact of certain provisions of the 2018 Requirements on FDA-regulated clinical investigations.”

Informed Consent

In response to various questions and concerns from stakeholders, FDA states that “the provisions of the 2018 Requirements related to the content, organization, and presentation of information included in the consent form and process as well as the basic and additional elements of informed consent are not inconsistent with FDA’s current policies and guidances.”  As such, sponsors and investigators do not need to develop, and IRBs do not need to review two separate informed consent forms.

Expedited Review Procedures & List

21 CFR 56.110 outlines expedited IRB review procedures for certain kinds of research involving only minimal risk.  On November 9, 1998, FDA established and published a list of research categories that may be reviewed by an IRB through an expedited review procedure; and section 56.110(b) makes clear that, as appropriate, IRB “reviewer(s)” must find the research on the list to involve no more than minimal risk in order for the IRB to use the expedited review procedure.

FDA’s recent guidance document states that the Agency “recognizes that under the 2018 Requirements at 45 CFR 46.110(b), an IRB may use the expedited procedures for research appearing on the expedited review list, unless the IRB reviewer determines that the study involves more than minimal risk.”  However, because FDA’s regulations have not been revised, the guidance notes that IRBs must continue to comply with the regulations set forth in 21 CFR 56.110(b) and must use the 1998 list for FDA-regulated clinical investigations.

IRB Continuing Review

Under the 2018 Requirements, IRB continuing review is not required if:

  • The research is eligible for expedited review in accordance with 45 CFR 46.110
  • The research has progressed to the point that the only remaining activities are data analysis or accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care

However, FDA has not revised its regulations, which means that IRBs are required to comply with the Agency’s current requirements for IRB continuing review as outlined in 21 CFR 56.109(f).  This states that “IRBs are required to conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year.”

The general compliance date for the revised Common Rule is January 21, 2019.  After this date, any clinical investigation involving an FDA-regulated product that is conducted or supported by HHS is subject to both sets of regulations.  Furthermore, where regulations differ, FDA states that “the regulations that offer the greater protection to human subjects should be followed.”

We can help ensure that your clinical investigations are conducted in compliance with HHS & FDA human subject regulations.  To learn more about our services and how we can help you, contact us today.


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