Regulatory Environment


Good Clinical Practices (GCP) describes the obligations of the sponsor, monitors, investigators and Institutional Review Boards (IRB) in protecting human subjects, both in the laws governing clinical research and the ideals of research ethics and “good science.” Although many of its precepts are not legally binding (e.g., guidelines and information sheets issued by FDA), GCP is widely accepted and expected in clinical research. Failure to meet GCP standards may result in sanctions and penalties.

Laws. All the government-approved rules of conduct that are
in force over a certain territory (e.g., the “laws” of the US). An
example would be HIPAA (Health Insurance Portability and
Accountability Act).
Regulations (or rules). Promulgated by administrative agencies like FDA, using authority delegated to them by Congress. Often, regulations implement a statute or set procedures to allow an agency to exercise the authority delegated to it by Congress. New regulations are codified in the collection of all current regulations,  called the Code of Federal Regulations (CFR). Although they are not laws, regulations have the force of law, since they are adopted under authority granted by statutes and  often include penalties for violations.
Guidance/Guidelines. Provide assistance by explaining how a regulated industry may comply with those statutory and regulatory requirements. Guidance documents for industry do not establish legally-enforceable rights or responsibilities and are not legally binding.

Standards. Accepted or mandated obligations, behaviors, and ethical imperatives for one’s profession, such as a code of ethics, standards of care, etc.

Instruction Sheets and Standard Operating Procedures (SOPs). Detailed  instructions. FDA requires that IRBs have SOPs, but does not require sponsors or  investigative sites to have them.

CFR HHSMuch of the biomedical and behavioral research conducted in the United States is governed by the Department of Health and Human Services (HHS) or the Food and Drug Administration (FDA).

HHS Oversees federally-funded studies (e.g., NIH grants) and is governed by the Federal Policy for the Protection of Human Subjects (also known as the “Common Rule,” codified at sub-part A of Title 45 CFR Part 46). The main elements of the Common Rule include requirements for assuring compliance by research institutions, requirements for researchers obtaining and documenting informed consent, and requirements for IRB membership, function, operations, review of research, and record keeping.

In addition to the Common Rule, HHS has adopted three (3) subparts which provide additional protection for vulnerable populations. These include:

In addition to the Common Rule, HHS has adopted three (3) subparts which provide additional protection for vulnerable populations. These include:

  • Pregnant women, human fetuses, and neonates (Subpart B, 45 CFR 200, et. al.)
  • Prisoners (Subpart C, 45 CFR 301)
  • Children (Subpart D, 45 CFR 401)

FDA. Regulates all drugs, biologics, and devices used for diagnosis, treatment, and prevention of disease in humans and animals. Investigational products under FDA jurisdiction are highly regulated and are subject to several parts of Title 21 CFR:

  • Part 11 (Electronic records; electronic signatures)
  • Part 50 (Protection of Hu man Subjects)
  • Part 54 (Financial Disclosure)
  • Part 56 (Institutional Review Boards)
  • Part 312 (Investigational New Drug Application [IND])
  • Part 314 (Applications for FDA approval to market a new drug)
  • Part 600 (Biological Products)
  • Part 812 (Investigational Device Exemptions)
  • Part 814 (Premarket approval of medical devices)

NOTE: If you are conducting a study with an FDA-regulated product, you must follow FDA regulations. If you are con- ducting a federally-funded study, you must follow 45 CFR 46. If you are conducting a federally-funded study with an FDA- regulated product…you must follow both sets of regulations.

The Common Rule was adopted in 1991 following a decade in which different government agencies had different requirements. Each agency defines its own jurisdiction. Many regulate only their funded research; others regulate products or activities. FDA has concurred with the Common Rule, but did not adopt the Policy in its entirety. FDA regulations and the provisions of the Common Rule are similar, although some significant differences exist. Most government agencies require funded institutions to submit an agreement assuring that all appropriate rules and regulations will be followed. Others, like FDA, inspect and audit institutions to determine compliance. All agencies require the use of an IRB.

State and Local Laws

State and local laws and regulations supersede federal regulations as long as they are more restrictive and do not put the subject at increased risk. An investigator must be familiar with state and local regulations that may directly affect research, such as legal age of con sent, legal guardianship requirements, and informed con sent requirements.

International Regulatory Environment

International Conference on Harmonisation (ICH) Guidelines (  Regulatory authorities and industry associations have promoted international harmonization of regulatory requirements. One of the goals of the ICH is to identify and reduce differences in technical requirements for drug development within regulatory agencies among three region s: the European Union, Japan, and the United States. In the Federal Register of May 9, 1997, FDA adopted the ICH’s “Good Clinical Practice: Consolidated Guideline,’ representing the agency’s current thinking on good clinical practices. FDA chose to adopt the ICH GCP guidelines without making them regulation under the assumption that everything in the ICH GCP guidelines is already contained in current regulations.