All regulations issued by federal agencies under the statutory authority established by Congress are published in the Code of Federal Regulations (CFR).
HHS human subject protection regulations at 45 CFR part 46 were first issued in 1974. In 1978, the National Commission or the Protection of Human Subjects of Biomedical and Behavioral Research published “Ethical Principles and Guidelines for the Protection of Human Subjects of Research,” also known as the Belmont Report, named after the Belmont Conference Center where the Commission met when drafting the report. The Belmont Report identifies three fundamental ethical principles for all human subjects research: respect for persons, beneficence, and justice.
The current version of the regulations includes five subparts.
Subpart A is the basic set of protections for all human subjects of research conducted or supported by HHS, and was revised in 1981 and 1991, with technical amendments made in 2005.
Three of the other subparts provide added protections for specific vulnerable groups of subjects.
- Subpart B, issued in1975, and most recently revised in 2001, provides additional protections for pregnant women, human fetuses, and neonates involved in research.
- Subpart C, issued in 1978, provides additional protections pertaining to biomedical and behavioral research involving prisoners as subjects.
- Subpart D, issued in 1983, provides additional protections for children involved as subjects in research.
Subpart E, issued in 2009, requires registration of institutional review boards (IRBs) which conduct review of human research studies conducted or supported by HHS.
The Common Rule
In 1991, the “Federal Policy for the Protection of Human Research Subjects,” informally known as the “Common Rule” was issued by 15 federal departments and agencies. The Common Rule was based on the HHS 45 CFR part 46 subpart A, and includes identical language in the separate regulations of those departments and agencies. Technical amendments were made to the Common Rule in 2005. One additional agency (the Central Intelligence Agency) is required to follow the Common Rule by executive order, and one additional department (the Department of Homeland Security) chose to follow all HHS subparts. Other departments and agencies have adopted one or more of the other HHS subparts and some have their own additional human subject protection regulations.
For a complete listing of the agencies that follow the Common Rule please click here.
The Food and Drug Administration (FDA) is an HHS agency that regulates clinical investigations of products under its jurisdiction, such as drugs, biological products, and medical devices. FDA regulations are published in title 21 of the CFR. FDA’s human subject protection regulations include:
21 CFR part 50, Protection of Human Subjects
21 CFR part 56, Institutional Review Boards
21 CFR part 312, Investigational New Drug Application
21 CFR part 812, Investigational Device Exemptions
21 CFR part 50 “Protection of human subjects,” issued in 1980, amended in 1981, 1989, 1990, 1991, 1996, 1997, 1999, 2006, and 2011, applies to informed consent by research subjects. Subpart D was added to 21 CFR part 50 in 2001 and provides additional protections for children involved in clinical investigations.
21 CFR part 56, issued in 1981 and amended in 1989, 1991, 1996, 1999 , 2000, 2001, 2002, and 2009, applies to IRBs.
Other FDA regulations that apply to clinical investigations include 21 CFR part 54, Financial Disclosure by Clinical Investigators.