History of Federal Regulations

U.S. Food and Drug Administration

MM Marshall QAO

History of Food and Drug Laws

FDA has grown from a single chemist in the US Department of Agriculture in 1862 to a staff of 9,100 employees in 2001….comprising chemists, pharmacologists, physicians, microbiologist, veterinarians, pharmacists, lawyers and many others.

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.

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.

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…

           

Massengill distributed this preparation without testing for safety (which was not required by law).

Continuing problems with dangerous drugs that fell outside the parameters of the Pure Food and Drugs Act finally received national attention with the Elixir Sulfanilamide disaster in 1937.

. Because it contained diethylene glycol as a vehicle, a chemical analogue of antifreezeantifreeze, 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.

all new drugs be proved safe before marketing

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.

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

Durham-Humphrey Amendment

(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 . . .

Merrell Pharmaceutical company of Cincinnati 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.

• Kelsey asked for more data; she was concerned that drug acted differently in animals than it did in humans (it wasn’t a sedative in animals).

• Merrell officials went to Washington to complain, but FDA officials held firm.

• 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 Merrell to conduct studies to show that drug could safely be taken by pregnant women without harming the fetus.

• Merrell officials were appalled that this “stubborn bureaucrat” could derail their plans for marketing a sure-fire best seller . . . Dr. Kelsey held firm and as did her supervisors at FDA.

• Long before Merrell could complete its tests . . . news broke of a terrible deformity in babies born with tiny flipper-like stumps instead of arms and hands. 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] Merrell was permitted to provide free samples to physicians as soon as the company applied for FDA licensing permission.

Frances Kelsy received the Distinguished Federal Civilian Service Award from President John F. Kennedy August 1962.

•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 Searle 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 clinical use of ALG [antilympocyte golbulin].

The investigator, was world renown for transplant surgery.

Grand jury probe that subpoenaed 22 years’ worth of records.

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”

The University culture …..is no excuse for not following GLP regulations…..says FDA

University is responsible for compliance of laboratories who tell sponsors that they can do GLP Studies

Federal regulations are government documents describing the rules!

is the codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government

Code of Federal Regulations (CFR)

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….

A word about regulations…..

They are the law and therefore following the law means compliance.

As lab managers, senior technologist or project managers…..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 non-clinical 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’ ReliefPart 16 Protection of Human Subjects

Title 42 CFR Public HealthPart 50 Polices of General ApplicabilitySubpart 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 WelfareSubtitle A Department of Health and Human

ServicesPart 46 Protection of Human SubjectsPart 160 General Administrative Requirements Part 164 Security and Privacy

Questions ??