U. S. FDA created the original Food and Drugs Act, which prohibited inter-state commerce in misbranded and adulterated food, drink and drugs.

FDA passed Federal Food, Drug and Cosmetic Act, which required that new drugs be shown to be safe before marketing.

The Nuremberg Code arose as part of the trial of the United States versus Karl Brandt. Karl Brandt and others were tried at Nuremberg for crimes against humanity committed in their roles as the Nazi High Command. One of the ten requirements of the Nuremberg Code is that "The voluntary consent of human subject is absolutely essential".

Thalidomide tragedy a drug prescribed for morning sickness resulted in thousands of babies born with phocomelia (seal limbs). This was the trigger for regulatory guidelines in many European countries.

Kefauver-Harris amendment in the U.S required

• Evidence of efficacy before approval
• Evidence of safety before testing in humans
• Protection of humans in research
• Active review of test data before approval

The eighteenth World Medical Assembly at Helsinki, Finland, adopted a code of ethics for the guidance of doctors involved in clinical research. This is popularly known as the “Declaration of Helsinki.” The “Declaration of Helsinki” was revised in 1975, 1981, 1983 and 1989. The latest revision was made in October 1996 in Republic of South Africa, and physicians conducting clinical research now internationally follow this

In the U.S. regulations protecting human subjects first became effective. The regulations established the Institutional Review Board (IRB)/ Ethics Committees (ECs) as one of the mechanisms through which human subjects would be protected.

The National Commission for the Protection of Human Subjects of Biological and Behavioral Research submitted a report entitled "The Belmont Report". The report sets forth the ethical principles underlying the acceptable conduct of research involving human subjects. These principles are now accepted as the three quintessential requirements for ethical conduct of research involving human subjects, These are:

	Respect for persons involves recognition of the personal dignity and autonomy of individuals and special protection of those persons with diminished autonomy
	Beneficence entails an obligation to protect persons from harm by maximizing anticipated benefit and minimizing possible risks of harm.
	Justice requires that the benefits and burdens of research be distributed fairly.