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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Compliance Program 7348.809 - Part I - Background

Since the Investigational New Drug (IND) Regulations went into effect in 1963, the Food and Drug Administration (FDA) has exercised oversight of the conduct of clinical studies involving FDA-regulated products. The Bioresearch Monitoring Program (BIMO) was established in 1977 by a task force that included representatives from the drug, biologic, device, animal drug, and food areas.

Compliance programs (CP) were developed to provide uniform guidance and specific instructions for inspections of Clinical Investigators (CP 7348.811), Sponsors (CP 7348.810), In-Vivo Bioequivalence facilities (CP 7348.001), Institutional Review Boards (CP 7348.809), and Nonclinical Laboratories (CP 7348.808).

The Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act (the FD&C Act) increased FDA’s regulatory authority over the clinical testing of new drugs. With the passage of the Kefauver-Harris Amendments, the Medical Device Amendments of 1976, and other legislation, FDA has been provided additional safeguards to protect the rights, safety and welfare of human subjects who participate in investigational trials involving FDA-regulated articles.

Congress has given a mandate to institutional review boards (IRBs) to oversee research involving human subjects that is being conducted using FDA-regulated articles. FDA has published regulations that set forth standards and procedures for IRBs in 21 CFR Part 56, which became a final rule in the Federal Register (FR) on January 27, 1981 (46 FR 8958 – “Protection of Human Subjects; Standards for Institutional Review Boards for Clinical Investigators”). The requirements for informed consent, which are found in 21 CFR Part 50,1 were published as a final rule in the Federal Register (FR) on the same date (46 FR 8942, January 27, 1981; “Protection of Human Subjects; Informed Consent”).

The above regulations require IRB review of all clinical investigations using test articles regulated by FDA under sections 505(i) and 520(g) of the FD&C Act, as well as clinical investigations conducted in support of applications for research or marketing permits for other articles regulated by the agency. The rewrite of the investigational new drug (IND) application regulations on March 19, 1987, includes informed consent and IRB review as conditions for exempting from the IND requirements certain studies involving marketed drugs (21 CFR 312.2(b)(1)(iv)). Similar conditions are included in the IDE regulations (21 CFR 812.2(b)) for abbreviated requirements of certain categories of device investigations.

On June 18, 1991, the Federal Policy for the Protection of Human Subjects; Final Rule (Common Rule) was published in the FR (56 FR 28003).2 These regulations set forth requirements for the protection of human subjects involved in research conducted or funded by 15 Federal departments and agencies, including the Department of Health and Human Services. In the same issue of the FR (56 FR 28025), amendments to the FDA regulations on IRBs and on informed consent requirements were published; these amendments bring 21 CFR Parts 50 and 563 into conformity with the above Federal Policy. Existing FDA regulations governing the protection of human subjects share a common core with the Federal Policy, and implement the fundamental principles embodied in that policy. The Federal Policy and the FDA amendments of 21 CFR Parts 50 and 56 became effective on August 19, 1991.4

Please note that there are some differences between the Department of Health and Human Services (DHHS) human subject protection regulations found at 45 CFR 46 and the FDA human subject protection regulations found at 21 CFR Parts 50 and 56. IRB written procedures that are compliant with the DHHS requirements will not necessarily be compliant with FDA regulations, i.e., IRBs that are subject to 45 CFR Part 46 will need to ensure that their SOPs are in compliance with both sets of regulations. FDA inspections, however, should only focus on FDA’s regulations.


1www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm113818.htm
2www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm118862.htm
3www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm118296.htm
4http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm118893.htm