History of Federal
Regulations
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….
•
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
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”
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 SpanishAmerican 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…
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.
Massengill distributed this
preparation without testing for safety
(which was not required by law).
.
Because
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.
 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 . . .
A Pharmaceutical company of
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).
•
Company 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 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” could derail
their plans for marketing a sure-fire
best seller . . . Dr. Kelsey held firm and
as did her supervisors at FDA.
• 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. All the baby’s mothers had
taken the drug thalidomide in the first
20-40 days of pregnancy.
Frances Kelsy
received the Distinguished
Federal Civilian Service
Award from President John
F. Kennedy August 1962.
• 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.
•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 investigaitonKenndy 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
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!
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

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
Questions ??