Comparison of FDA and HHS Human Subject Protection Regulations
|FDA Regulations||HHS Regulations|
IRBs that review clinical investigations regulated by the FDA under sections 505(i), 507(d), and 520(g) of the act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the FDA, including food and color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products.
All research involving human subjects conducted or supported by HHS or conducted in an institution that agrees to assume responsibility for the research in accordance with 45 CFR 46 regardless of the source of funding.
56.102 and 50.3 Definitions
Definitions for "Act"; "Application for researchor marketing permit"; "Emergency use"; "Sponsor"; "Sponsor-investigator"; "Test article" do not have comparable terms defined in 45 CFR 46.
FDA has defined "clinical investigation" to be synonymous with "research". "Clinical investigation" means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA...or the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit.
"Human subject" means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.
"Institutional Review Board" means any board, committee, or other group formally designated by an institution to review, to approve the initiation or, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. The term has the same meaning as the phrase "institutional review committee" as used in section 520(g) of the act.
Definitions for "Department or agency head"; "Certification" do not have comparable terms defined in 21 CFR 50 or 56
HHS has defined "research" as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
HHS has defined "Research subject to regulation" and similar terms as intending to encompass those research activities for which a federal department or agency has specific responsibility for regulating as a research activity, (for example, Investigational New Drug requirements administered by the FDA).
"Human subject" means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
"IRB" means an institutional review board established in accord with and for the purposes expressed in this policy.
56.103 Circumstances in which IRB review is required.
46.103 Assuring compliance with this policy--research conducted or supported by any Federal Department or Agency
Sections dealing with assurances and certifications (a), (b)(1)-(3), (c)-(f) are unique to the common rule and the HHS regulations.
56.104 Exemptions from IRB requirement
46.101(b) Exemptions from this policy
56.105 Waiver of IRB requirement.
On the application of a sponsor or sponsor-investigator, the FDA may waive any of the requirements contained in these regulations, including the requirement for IRB review, for specific research activities or for classes of research activities, otherwise covered by these regulations.
No comparable provision.
56.107 and 46.107 IRB Membership requirements are identical
56.108 and 46.108 "IRB functions and operations" are virtually identical except 56.108 requires reporting to the FDA; 46.108 requires reporting to the department or agency head.
56.109 and 46.109 "IRB review of research" are virtually identical with the following exceptions:
56.110 and 46.110 "Expedited Review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research" are virtually identical, except:
56.111 and 46.111 "Criteria for IRB approval of Research" are virtually identical except 56.111 contains references to sections in part 50 and 46.111 contains references to sections in part 46.
56.112 and 46.112 "Review by institution" are identical.
56.113 and 46.113 "Suspension or termination of IRB approval of research" are virtually identical except 56.113 refers to FDA and 46.113 refers to the department or agency head.
56.114 Cooperative research
In complying with these regulations, institutions involved in multi-institutionalstudies may use joint review, reliance upon the review of anotherqualified IRB, or similar arrangements aimed at avoidance of duplicationof effort.
46.114 Cooperative research
Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with this policy. With the approval of the department or agency head, an institution participating in a cooperative project may enter into a joint review arrangement, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort.
56.115 and 46.115 "IRB Records" are virtually identical except
56.120 Lesser administrative actions
The agency may
The parent institution is presumed to be responsible for the operation of an IRB, and FDA will ordinarily direct any administrative action against the institution. However, depending on the evidence of responsibility for deficiencies, determined during the investigation, FDA may restrict its administrative actions to the IRB or to a component of the parent institution determined to be responsible for formal designation of the IRB.
46.123 Early termination of research support; Evaluation of applications and proposals.
56.121 Disqualification of an IRB or an institution
...The Commissioner may disqualify an IRB or the parent institution if the Commissioner determines that:
46.120 Evaluation and disposition of applications and proposals for research to be conducted or supported by a Federal Department or Agency
The department or agency head will evaluate all applications and proposals involving human subjects.... This evaluation will take into consideration the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. On the basis of this evaluation, the department or agency head may approve or disapprove the application or proposal, or enter into negotiations to develop an approvable one.
46.122 Use of Federal Funds
Federal Funds administered by a department or agency may not be expended for research involving human subjects unless the requirements of this policy have been satisfied.
56.122 Public disclosure of information regarding revocation
A determination that the FDA has disqualified an institution and the administrative record regarding that determination are disclosable to the public under part 20.
56.123 Reinstatement of an IRB or an institution
An IRB or an institution may be reinstated if the Commissioner determines...that the IRB or institution has provided adequate assurance that it will operate in compliance with the standards set forth in this part....
No comparable provisions.
56.124 Actions alternative or additional to disqualification
Disqualification of an IRB...is independent of...other proceedings or actions authorized by the Act. The FDA may, at any time, through the Department of Justice institute any appropriate judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or in lieu of, and before, at the time of or after disqualification. The agency may also refer pertinent matters to another Federal, State, or local government agency for any action that that agency determines to be appropriate.
With respect to any research project...the department...head may impose additional conditions prior to or at the time of approval when in the judgment of the department or agency head additional conditions are necessary for the protection of human subjects.
50.20 and 46.116 General requirements for informed consent are virtually identical.
50.25 and 46.116(a) Elements of informed consent are virtually identical except:
50.27 and 46.117 Documentation of informed consent are virtually identical except:
50.23(a)-(c) Exception from general requirements
Describes an exception from the general requirements for obtaining informed consent in circumstances that are life-threatening; informed consent cannot be obtained from the subject; time is not sufficient to obtain consent from the subject's legal representative; and there is available no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject.
No comparable provisions
50.23(d) Waiver of informed consent for military personnel
Describes the criteria and standards that the President is to apply in making a determination that informed consent is not feasible or is contrary to the best interests of the individual in military exigencies in accordance with the Strom Thurmond Defense Authorization Act for FY 1999
No comparable provision.
- In 1991 FDA's regulations were harmonized with the common rule to the extent permitted by statute.
- Differences in the rules are due to differences in the statutory (1) scope or (2) requirements.
- FDA has additional IRB requirements contained in parts 312, 812, and 814. For example, 812.2(b)(ii) states that research is considered to have an approved application for an IDE, unless FDA has notified the sponsor to the contrary, if IRB approval of the investigation is obtained after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk, and maintains such approval, (iii) and ensures informed consent is obtained in accordance with part 50.
- HHS has special subparts relating to vulnerable populations, e.g., children, prisoners, pregnant women, etc. FDA does not have comparable provisions for these populations.
- The HHS regulations require assurances and certifications from the grantee institution. FDA regulations generally require assurances of compliance from either or both the sponsor of the research and the clinical investigator.
Content prepared by: Bonnie M. Lee, FDA, 2000