Information for Investigators: Federal Regulations

Federal Regulations – The field of human subjects research is governed by several sets of regulations. Links to these regulations and a brief description of the purpose of the regulation are provided below for reference. The IRB forms and checklists are designed to address the requirements of these regulations and aid investigators and study personnel in ensuring compliance.

Office for Human Research Protections Regulations

45 Code of Federal Regulations (CFR) Part 46 – Protection of Human Subjects
Subpart A of this regulation is often referred to as The Common Rule because several agencies abide by it. Subpart A is titled Basic HHS Policy for Protection of Human Research Subjects. Some of the key elements addressed within 45 CFR 46 include the following:

• IRB membership
• IRB functions and operations
• IRB review of research
• Expedited review procedures
• Criteria for IRB approval
• General requirements for informed consent
• Documentation of informed consent

Subparts B, C and D address the additional protections required for vulnerable populations. Subpart B addresses additional protections for pregnant women, human fetuses and neonates. Subpart C addresses additional protections for prisoners. Subpart D addresses additional protections for children. All human subject research conducted at the Health Center, regardless of the source of funding must comply with Subpart A and when applicable Subparts B, C or D.  

Food and Drug Administration Regulations

21 CFR 50 – Protection of Human Subjects
This regulation applies to all clinical investigations regulated by the Food and Drug Administration under sections 505(i) and 520(g) of the Federal Food, Drug and Cosmetic Act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration, including foods, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, medical devices for humans use, biological products for human use and electronic products. This regulation consists of Subparts A, B and D. Subpart A addresses general provisions of the regulation, e.g. scope and definitions. Subpart B addresses informed consent of human subjects. Subpart D address the additional protections for children. The requirements of 21 CFR 50 Subparts B and D are very similar to the requirements put forth in Part 46. Investigators must comply with both sets of regulations. Some of the key elements addressed within subpart B include the following:

• General requirements of informed consent
• Exceptions from the general requirements
• Exceptions from informed consent requirements for emergency research
• Elements of informed consent
• Documentation of informed consent

21 CFR 56 – Institutional Review Boards
This regulation is very similar to 45 CFR 46 in that it addresses several of the same key elements, including:

• IRB membership
• IRB functions and operations
• IRB review of research
• Expedited review procedures
• Criteria for IRB approval

It also addresses issues of records and reports and administrative actions for noncompliance.

21 CFR 54 – Financial Disclosure by Clinical Investigators
The requirements in this part apply to any applicant who submits a marketing application for a human drug, biological product, or device and who submits covered clinical studies. The applicant is responsible for making the appropriate certification or disclosure statement where the applicant either contracted with one or more clinical investigators to conduct the studies or submitted studies conducted by others not under contract to the applicant. Some of the key elements addressed include:

• Certification and disclosure requirements
• Agency evaluation of financial interests
• Recordkeeping and record retention

21 CFR 210-211 - Good Manufacturing Practices
These regulations set forth the minimum standard for manufacturing, processing, packing or holding of drugs.

21 CFR 312 – Investigational New Drug Application
This regulation applies to all clinical investigations of products that are subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to the licensing provisions of the Public Health Service Act. Key elements addressed within the regulation include:

• Subpart B - Investigational New Drug Applications
• Subpart C - Administrative Actions
• Subpart D - Responsibilities of Sponsors and Investigators
• Subpart E - Drugs Intended to Treat Life-threatening or Severely Debilitating Illnesses

21 CFR 314 - Application for FDA Approval to Market a New Drug
This part of the regulations sets forth procedures and requirements for the submission to, and the review by, the Food and Drug Administration of applications and abbreviated applications to market a new drug under section 505 of the Federal Food, Drug, and Cosmetic Act, as well as amendments, supplements, and postmarketing reports to them

21 CFR 812 – Investigational Device Exemptions
This regulation applies to clinical investigations of devices to determine safety and effectiveness. Key elements addressed within the regulation include:

• Subpart B - Application and Administrative Action
• Subpart C - Responsibilities of Sponsors
• Subpart D - IRB Review and Approval
• Subpart E - Responsibilities of Investigators
• Subpart G - Records and Reports

21 CFR 803 - Medical Device Reporting
This part establishes requirements for medical device reporting. Under this part, device user facilities, importers, and manufacturers, as defined in § 803.3, must report deaths and serious injuries to which a device has or may have caused or contributed, must establish and maintain adverse event files, and must submit to FDA specified followup and summary reports.

21 CFR 814 - PreMarket Approval of Medical Devices
This part provides procedures for the premarket approval of medical devices intended for human use.  

21 CFR 600 - Biological Products General

21 CFR 601 - Licensing

U.S. Department of Heath and Human Services Regulations – Office of Civil Rights Regulations

45 CFR 160 and 164 (PDF) – Health Insurance Portability and Accountability Act (HIPAA)
The Privacy Rule establishes, for the first time, a foundation of Federal protections for the privacy of protected health information. The Rule does not replace Federal, State, or other law that grants individuals even greater privacy protections, and covered entities are free to retain or adopt more protective policies or practices.

Department of Education

20 U.S.C. § 1232h; 34 CFR Part 98 - Protection of Pupil Rights Amendment
The Protection of Pupil Rights Amendment (PPRA) (20 U.S.C. § 1232h; 34 CFR Part 98) applies to programs that receive funding from the U.S. Department of Education (ED). PPRA is intended to protect the rights of parents and students by ensuring that 1) schools and contractors make instructional materials available for inspection by parents if those materials will be used in connection with an ED-funded survey, analysis, or evaluation in which their children participate and 2) schools and contractors obtain written parental consent before minor students are required to participate in any ED-funded survey, analysis, or evaluation that reveals sensitive and/or private information.