History of Federal Regulations

History of Federal Regulations History of Food and Drug Laws Food and Drug Administration MM Marshall QAO FDA has grown from a single chemist in the US Department of Agriculture in 1862 to a staff of 9,100 employees in 2001. FDA left the Department of Agriculture in 1940 and joined the Federal Security Agency and joined the Department of Health and Human Services in 1980. Today comprising chemists, pharmacologists, physicians, microbiologist, veterinarians, pharmacists, lawyers and many others. History of Food and Drug Laws History of Food and Drug Laws In 1902. Volunteers poison squad of young men agreed to eat only foods treated with measured amounts of chemical, with the object of demonstrating whether these ingredients were injurious to health. Harvey Washington Wiley Offered the position of Chief Chemist in the US Dept of Agriculture in 1882 Earned the title Father of the Pure Food and Drug Act This initiated many news articles in the 1902-1906 years Packers blamed with shipping embalmed beef that sickened troops in the Spanish- American War. Upton Sinclair published the The Jungle describing the filthy conditions in Chicago s meat packing plants in 1906. History Nauseating story of the plight of workers in the food processing industry around Chicago Public was horrified by the food processing, not the workers Need for regulation at the Federal level, as each state had its own laws Marilyn Marshall 1

Strenuous opposition.from: Whiskey distillers and patent medicine firms, who were the largest advertisers in the country. It was argued, the Federal Government had no business policing what people ate, drank, or used for medicine. However, support came from the vote less but militant club women of the country who rallied to the pure food cause and.. President Theodore Roosevelt who used his weigh decisively to ensure that this time Congress would not adjourn, as so often before until the food bill was passed. 1906 Food and Drugs Act became law to control adulterated and misbranded drugs and food in interstate commerce. However assurances of safety issues were not mandated Still unclear as to new drugs. And Continuing problems with dangerous drugs that fell outside History the parameters of the Pure Food and Drugs Act, finally received national attention with the Elixir Sulfanilamide disaster in 1937. Massengill distributed this preparation without testing for safety (which was not required by law). It contained diethylene glycol as a vehicle, a chemical analogue of antifreeze, Over 100 people died, many of whom were children. Provisions lacking in the 1906 law were corrected in 1938 President Franklin D. Roosevelt signed the Federal Food, Drug, and Cosmetic Act. therapeutic devices and cosmetics become subject to regulation standards of identity and quality be instituted for foods formalized FDA s ability to conduct factory inspections. Marilyn Marshall 2

Durham-Humphrey Amendment This remains the basic law we have today with numerous amendments and other acts which broaden FDA s responsibilities considerably. The goal for FDA is above all else to safeguard the health and well being of the American people (1951) clarified the vague line between prescription and nonprescription drugs The Amendment specifically stated: dangerous drugs, defined by several parameters, could not be dispensed without a prescription, witnessed by the prescription legend: "Caution: Federal law prohibits dispensing without prescription." Interesting development in 1960... A Pharmaceutical company applied to FDA for permission to market a drug [very popular sleeping pill in Europe] in the US. Application was assigned to new staff member Frances O. Kelsey asked for more data concerned that drug acted differently in animals than it did in humans (it wasn t a sedative in animals). During this time a single report in a British journal, indicated that some long term users of this drug developed nerve damage in their hands and feet. Dr. Kelsey asked the company to conduct studies to show that drug could safely be taken by pregnant women without harming the fetus. Company officials were appalled that this stubborn bureaucrat Long before the Company could complete its tests... news broke of a terrible deformity in babies born with tiny flipper-like stumps instead of arms and hands. Frances Kelsy received the Distinguished Federal Civilian Service Award from President John F. Kennedy August 1962. All the baby s mothers had taken the drug thalidomide in the first 20-40 days of pregnancy 17 American babies were born with the deformity because [at the time] the company was permitted to provide free samples to physicians as soon as the company applied for FDA licensing permission. Marilyn Marshall 3

Congress responded to thalidomide tragedy by passing the Kefauver-Harris drug law in 1962 This law, for the first time, gave FDA.. the power to require specific procedures for testing new drugs for safety and effectiveness. However.. In the 70 s FDA s investigation into sloppy and fraudulent research resulted in the Senate investigaiton- Kenndy Hearings and the conclusion to the hearings stated that. Findings of the Senate Committee on review of documents of the Drug company found that personnel did not. assure the accuracy of data which are transcribed from original documents to final reports make accurate observations of the appropriate parameters and to document their observations promptly, and accurately, and to sign and date records of such observations Lack of understanding appears to stem from [1] insufficient appreciation by managers of the need for instruction and indoctrination of personnel in laboratory methods [2] An absence of established, written laboratory procedures and [3] A general lack of attention to routine quality assurance procedures and correction of deficiencies So. Chapter 1, Title 21 Regulatory Sections of the Code of Federal Regulations [CFR] 58 21 CFR 58 1978: Original Regulation 1987;1997 Amendments Regulations are for all to follow. 1992 FDA officials marched into the office of the University of Minnesota President to announce that the agency had imposed a hold on a Clinical Study The investigator, was world renown for transplant surgery. Grand jury indictment Marilyn Marshall 4

There were many factors.. But several crucial GLP deviations.. Paper work didn t get done. PI saw himself, says a former colleague as a pacesetter who was moving the field of transplant surgery forward, someone who couldn t be bothered with the details of the rules because he was changing the rules Federal regulations are government documents describing the rules! Code of Federal Regulations (CFR) is the codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government History Code of Federal Regulations (CFR) which establishes the laws under which some 50 different government agencies operate and exert their influence. 21 CFR is the FDA [Food and Drug Administration] 45 CFR is the DHHS [Department of Human Health and Safety] 40 CFR is EPA [Environmental Protection Agency] 12 CFR is Banking 6 CFR is Homeland Security Marilyn Marshall 5

Federal Register Published by the Office of the Federal Register, National Archives and Records Administration (NARA), the Federal Register is the official daily publication for rules, proposed rules, and notices of Federal agencies and organizations, as well as executive orders and presidential documents. Regulations.. They are the law and therefore following the law means compliance. As lab managers, senior technologist or project managers, Study Directors..know the regulations! This course is an introduction to the world of some federal regulations but not all. Regulations are amended so be a web warrior and be in compliance. Federal regulations for GLP nonclinical studies are to safeguard the health and well being of the American people 21 CFR 58 40 CFR 160 40 CFR 792 Title 21 CFR 50 Protection of Human Subjects Investigators Title 21 CFR 56 Institutional Review Boards Title 21 CFR 312 Investigational New Drug Application Title 21 CFR 812 Investigational Device Exemptions Title 21 CFR 801 Labeling Title 21 CFR 803 Medical Device Reporting Title 21 CFR 806 Medical Devices; Reports of Corrections and Removals Title 21 CFR 820 Quality System Regulation Title 38 CFR Pensions, Bonuses, and Veterans Relief Part 16 Protection of Human Subjects Title 42 CFR Public Health Part 50 Polices of General Applicability Subpart A Responsibility of PHS Awardee and Applicant Institutions for Dealing With and Reporting Possible Misconduct in Science Part 1003 Possession, Use, and Transfer of Selected Agents and Toxins Title 45 CFR Public Welfare Subtitle A Department of Health and Human Services Part 46 Protection of Human Subjects Part 160 General Administrative Requirements Part 164 Security and Privacy Marilyn Marshall 6

Questions?? Marilyn Marshall 7