Chapter 3
Federal Regulation of Drug
Products
Jahangir Moini, MD, MPH, CPhT
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Pure Food and Drug Act of 1906
• Prohibited interstate distribution or sale of
adulterated (made impure) and misbranded
(improperly labeled) food and drugs
• Amended almost 30 years later
• Sherley Amendment, enacted by Congress
in 1912, first regulated labeling
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Pure Food and Drug Act of 1906
• Key Points
– Prevented the manufacture, sale, transportation
and trafficking of impure, misbranded,
poisonous, or harmful:
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Drugs
Foods
Liquors
Medicines
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Harrison Narcotics
Tax Act of 1914
• Implemented to regulate and tax the
distribution, importation, and production of
opiates, including:
– Opium products
– Coca products (used to manufacture cocaine)
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Harrison Narcotics
Tax Act of 1914
• Key Points
– Intended to control commerce of opiates
and cocaine
– Required drug manufacturers, sellers,
distributors, importers, compounders, and
dispensers to register with Internal Revenue
Service (IRS)
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Sulfanilamide Tragedy of 1937
• Massengill introduced Elixir Sulfanilamide,
which contained diethylene glycol
• Used for streptococcal infections
• Not tested for toxicity
• More than 100 patients died before FDA
removed it from the market
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Food, Drug, and
Cosmetic Act of 1938
• Required pharmaceutical manufacturers to
file New Drug Application with the FDA
• Drug, food, and cosmetic manufacturers had
to ensure purity, strength, and packaging of
products
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Food, Drug, and
Cosmetic Act of 1938
• Gave FDA the power to approve or deny
new drug applications and conduct
inspections to ensure compliance
• Requires FDA approval of investigational
use of drugs on humans and ensures that
approved drugs are safe and effective
• Beginning of “pre-market approval process”
for drugs in U.S.
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Food, Drug, and
Cosmetic Act of 1938
• Key Points
– Required drugs to be labeled with adequate
directions to ensure safe use
– Controlled cosmetic products and medical
devices
– Required all drugs to have FDA approval
before they could be marketed
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Durham-Humphrey
Amendment of 1951
• During 1940s, FDA began to use internal
regulations to create classifications of
prescriptions (legend) drugs, and nonprescription (over-the-counter [OTC])
drugs–process did not work very well
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Durham-Humphrey
Amendment of 1951
• Amendment created to prohibit dispensing
of legend drugs without a prescription, but
did not restrict OTC drugs for sale and use
under medical supervision
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Durham-Humphrey
Amendment of 1951
• Key Points
– Required that drugs intended for use by humans
not safe to use without medical supervision be
dispensed only by prescription
– Required that legend drugs be labeled:
“Caution: Federal law prohibits dispensing
without prescription”
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Thalidomide Tragedy of 1962
• Thalidomide was marketed in 1958 and sold
without prescription as a tranquilizer in
West Germany until 1961, when it was
recognized as causing polyneuritis
• Later in 1961, it was first believed to cause
phocomelia (seal limbs), a severe birth
defect
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Thalidomide Tragedy of 1962
• Withdrawn from West German market in
November 1961
• In U.S., thalidomide distributed
experimentally in 1960 under the trade
name Kevadon® without final FDA
approval
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Thalidomide Tragedy of 1962
• Over 29,000 patients had been involved in
human clinical trials
• Cases of phocomelia reported in infants
born after mothers had taken Kevadon
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Kefauver-Harris
Amendment of 1963
• Further amended Federal Food, Drug, and
Cosmetic Act to require that drug products
(prescription and non-prescription) be
effective
• Prescription drug advertising placed under
FDA supervision and qualifications of drug
investigators subjected to review
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Kefauver-Harris
Amendment of 1963
• Key Points
– Required that all drug manufacturers prove
efficacy of drugs to FDA before marketing
– Required controlled drug studies and informed
consent of patients participating
– Required all drugs marketed since 1938 meet
the same requirements
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Comprehensive Drug Abuse
Prevention and Control Act of 1970
• Requires pharmaceutical industry to
maintain physical security and strict record
keeping for many types of drugs
• Main achievement was to divide controlled
substances into five schedules
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Comprehensive Drug Abuse
Prevention and Control Act of 1970
• Title II is known as the Controlled
Substances Act (CSA)
• Drug Schedules
– Schedule I – highest potential for abuse
– Schedule V – lowest potential for abuse
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Comprehensive Drug Abuse
Prevention and Control Act of 1970
• Drugs may be added or deleted from schedules,
or changed to a different schedule, based on
DEA or Department of Health and Human
Services actions, or because of petitions by
individuals or companies
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Comprehensive Drug Abuse
Prevention and Control Act of 1970
• Key Points
– Designed to update all previous laws that
focused on use and sale of narcotics and
similarly dangerous substances
– Possession of many substances was made
illegal and harsh penalties imposed
– Established standards to deal with drug abuse
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Poison Prevention Packaging
Act of 1970
• Authorized Consumer Product Safety
Commission to create standards for childresistant packaging
• “Special packaging” terminology requires
containers to be very difficult for young
children to open
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Poison Prevention Packaging
Act of 1970
• Requires a few OTC drugs and nearly all
legend drugs be packaged in child-resistant
containers
• If a prescriber authorizes non-child-resistant
containers, they may be provided by the
pharmacist (commonly for elderly or
handicapped patients)
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Poison Prevention Packaging
Act of 1970
• Commonly labeled “Package Not Child
Resistant” or “This Package For
Households Without Young Children”
• Require signed release form confirming
patient’s request for them to be used
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Poison Prevention Packaging
Act of 1970
• Key Points
– Requires certain substances be packaged to
make it difficult for children younger than 5
years to open them
– Same packaging should be easy for most adults
to open
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Occupational Safety and
Health Act (OSHA) of 1970
• Passed to prevent workplace disease and
injuries
• General purpose is to require all employers
to ensure employee safety and health
• Established Occupational Safety and Health
Administration (OSHA)
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Occupational Safety and
Health Act (OSHA) of 1970
• Key Points
– Protects of workers in private sector as well as
governmental jobs
– Protects workers from:
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Chemicals
Lack of sanitation
Machinery
Noise
Extreme temperatures
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Drug Listing Act of 1972
• Each new drug assigned unique and
permanent code known as a National Drug
Code (NDC)
• Identifies manufacturer or distributor, drug
formulation, and size and type of packaging
• FDA uses code to maintain database of
drugs and detailed information
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Drug Listing Act of 1972
• Key Points
– Amended Food, Drug, and Cosmetic Act of
1938
– Required all drug manufacturers to list all
commercial products with FDA
– Requires drug product listings be updated
2 times per year
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Medical Device
Amendment of 1976
• The Food, Drug, and Cosmetic Act did not
control medical devices very stringently
• As a result, this amendment subjected
medical devices to different levels of
control, depending upon their function
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Medical Device
Amendment of 1976
• Key Points
– Classified medical devices according to risk
– Established 3 classes of devices
– Class I and II devices do not require pre-market
approval
– Class III devices must pass unique regulatory
requirements
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Resource Conservation and
Recovery Act of 1976
• Also referred to as Solid Waste Disposal Act
• Regulates handling of solid wastes and
authorizes environmental agencies to handle
cleanup of contaminated sites
• Regulates solid waste landfills
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Resource Conservation and
Recovery Act of 1976
• Key Points
– Regulates disposal of hazardous wastes
– Environmental agencies can order proper
cleanup of improperly disposed wastes
– Encourages development of comprehensive
solid waste management programs
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Drug Regulation Reform Act
of 1978 and Provisions
• Intended to revise Food, Drug, and Cosmetic
Act on many different levels
• Designed to:
– Increase consumer protection and information, and
FDA’s public accountability
– Encourage drug innovation and research/training
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Drug Regulation Reform Act
of 1978 and Provisions
 Improve FDA enforcement
 Promote competition and cost savings through
generic drugs
 Make additional drugs available
 Protect patient rights
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Drug Regulation Reform Act
of 1978 and Provisions
• Key Points
– Encouraged fairer FDA regulations
– Shortened time required to develop new drugs,
get approval, and bring them to market
– Intended to reduce costs of new drug
development
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Drug Recalls
• Manufacturers may determine that a drug
they manufacture has been shown to be
harmful to the public
• May issue a drug recall and inform FDA
• FDA may recommend drug be recalled by
manufacturer
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Drug Recalls
• Class 1 – serious potential for injury or death
• Class 2 – possibility of serious adverse effects
with potentially irreversible consequences
• Class 3 – potential of adverse effects even
though they are not very likely
• Market withdrawal – manufacturer decides to
correct something about the product
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Orphan Drug Act of 1983
• Offers federal financial incentives to
commercial and non-profit organizations for
development and marketing of drugs
previously unavailable in U.S.
• Previously, valuable new drugs with efficacy
for a disease affecting few people were not
developed because of monetary investment
and time needed to secure approval
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Orphan Drug Act of 1983
• Affects drugs used to treat diseases
affecting fewer than 200,000 people in U.S.
• Offers tax breaks and 7-year monopoly on
drug sales to induce companies to undertake
development and manufacturing of such
drugs
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Orphan Drug Act of 1983
• Key Points
– Helps manufacturers make profits on orphan
drugs
– Covers about 5,000 rare conditions
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Drug Price Competition and Patent
Term Restoration Act of 1984
• Gave marketers of generic drugs ability to
file “abbreviated new drug applications” to
seek FDA approval
• Created to give more incentives to drug
manufacturers to offset time and money
required to bring new, innovative drug
products to market
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Drug Price Competition and Patent
Term Restoration Act of 1984
• In the pharmacy, “Orange” book used for
approval of drug products with therapeutic
equivalence
• Evaluates drug products to ensure safe
substitutions
• Also in electronic format, allowing easy
searching by many different categories
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Drug Price Competition and Patent
Term Restoration Act of 1984
• Key Points
– Amended the Food, Drug, and Cosmetic Act
– Created formal generic drug approval process
and established abbreviated new drug
application (ANDA) approval process
– Generic versions of innovator drugs approved
earlier could not get FDA approval without a
full new drug application
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Prescription Drug Marketing
Act of 1987
• Enacted to ensure that prescription drug
products are safe and effective, and avoid
tainting, counterfeiting, and misbranding
of drugs
• Main purpose to protect ability of drug
manufacturers to maintain different pricing
to different market segments
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Prescription Drug Marketing
Act of 1987
• Key Points
– Established specific prescription drug
distribution standards
– Encouraged distribution of authentic, properly
labeled, effective prescription drugs
– Required licensing of wholesalers and
regulation of blood centers
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Omnibus Budge Reconciliation
Act of 1990 (OBRA-90)
• Contained important amendments affecting
Medicare and Medicaid
• Main purpose to reduce Medicaid costs by
reducing inappropriate use of drugs by
Medicaid recipients
• Created tax limit cap on taxable income
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OBRA-90 Expansions
• Expanded rules about drug products to
ensure safest and most effective drug
therapy
• Helps patients save money while obtaining
quality medications
• Provides highest-quality care for residents
of nursing homes
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Omnibus Budget Reconciliation
Act of 1990 (OBRA-90)
• Key Points
– Requires pharmacists to review Medicaid
patients’ complete drug profiles before filling
prescriptions
– Must offer to discuss each patient’s drug
therapy regimen with patient
– State Medicaid programs must maintain Drug
Use Review Board
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FDA Safe Medical
Devices Act of 1990 (SMDA)
• Gives FDA increased ability to regulate
medical devices and products used for
medical diagnosis
• Requires medical devices reports to be filed
on a timely basis
• Established approval procedure for new
medical devices prior to marketing
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FDA Safe Medical
Devices Act of 1990 (SMDA)
• Key Points
– Requires facilities that use medical devices to
report if illness, injury, or death occurs because
of their use
– Controls method of reporting and protects those
who report
– Requires better manufacturer quality control
and tracking
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Anabolic Steroids
Control Act of 1990
• Allowed CSA to regulate anabolic steroids,
which promote muscle growth and are often
used illegally by athletes
• Anabolic steroids also known as
“performance-enhancing drugs”
• They have been shown to have serious
health consequences from overuse
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Anabolic Steroids
Control Act of 1990
• Key Points
– Put anabolic steroids into Schedule III of the
CSA
– Raised penalties for illegal distribution of these
agents or human growth hormone
– Resulted in prosecution of many foreign
companies distributing into U.S.
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Americans with Disabilities
Act of 1990
• Prohibits discrimination against disabled
persons
• Focuses on employment, public services,
transportation, public accommodations,
commercial facilities, and
telecommunications as they concern the
disabled
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Americans with Disabilities
Act of 1990
• Key Points
– Prohibits discrimination against the disabled
regardless of whether impairment is physical or
mental
– Provides clear standards of enforcement against
those who discriminate against the disabled
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Dietary Supplement Health
and Education Act of 1994
• Focused on how dietary supplements are
labeled and regulated
• Dietary supplements have always been
treated as foods, not drugs
• Holds dietary supplements manufacturers
responsible for safety of supplements
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Dietary Supplement Health
and Education Act of 1994
• Key Points
– Defined “dietary supplement”
– Enforced regulations against manufacturer of
dietary supplement claiming the supplement
actually treats or cures a specific condition
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Health Insurance Portability and
Accountability Act (HIPAA) of 1996
• Designed to improve continuity and
portability of health insurance, reduce
fraudulent activities, establish medical
savings accounts, improve long-term health
care access, and simplify health care
administration
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Health Insurance Portability and
Accountability Act (HIPAA) of 1996
• Sought to improve Medicare and Medicaid
• Developed national provider identifiers
(NPIs) for health care providers, employers,
and health insurance plans
• NPIs – unique ID numbers for covered
health care providers
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Health Insurance Portability and
Accountability Act (HIPAA) of 1996
• HIPAA regulations divided into:
– Privacy regulations
– Security regulations
– Transaction standards
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Health Insurance Portability and
Accountability Act (HIPAA) of 1996
• Key Points
– Protects health insurance coverage after job
loss or change
– Established national standards for health care
transactions
– Encourages electronic data interchange of
private health information
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FDA Modernization Act of 1997
• Designed to reform regulation of cosmetics,
food, and medical products
• Increased patient access to experimental
drugs and medical devices
• Mandated risk assessment reviews of all
foods and drugs containing mercury
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FDA Modernization Act of 1997
• Medicare Part D established to subsidize
prescription drug costs for Medicare
beneficiaries
• May be obtained by joining a prescription
drug plan (PDP) or a Medicare Advantage
(MA) plan
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FDA Modernization Act of 1997
• Key Points
– Passed to improve FDA regulation of drugs,
biological products, food, and medical devices
– Intended to speed up process
– Poised to address changing technologies and
marketing of products
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Medicare Prescription Drug,
Improvement, and Modernization
Act of 2003
• Also known as the Medicare Modernization
Act (MMA)
• Overhauled Medicare program more than any
other act
• Established a trial, partially privatized
Medicare system
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Medicare Prescription Drug,
Improvement, and Modernization
Act of 2003
• Key Points
– Provided entitlement benefit for prescription
drugs
– Used subsidies and tax breaks to help patients
afford medications they need
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Isotretinoin (Accutane®) Safety and
Risk Management Act of 2005
• Act was proposed but not passed
• Designed to restrict distribution of
isotretinoin because it caused severe birth
defects in fetuses of patients who took it
during pregnancy
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Isotretinoin (Accutane®) Safety and
Risk Management Act of 2005
• Key Points
– Designed to create a mandatory program
restricting distribution of Accutane and its
generic forms
– Asked for registry of all involved in its
distribution or use
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The Combat Methamphetamine
Epidemic Act of 2005
• Focused on the methamphetamine
provisions of the Patriot Act extension
• Intended to stop illegal use of
methamphetamine
• Drug trafficking, used to financially support
terrorism, now regulated by this act
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The Combat Methamphetamine
Epidemic Act of 2005
• Key Points
– Introduced safeguards to make ingredients used
in creation of methamphetamine and similar
drugs harder to access
– Gave government heightened powers to combat
drug smuggling, manufacture, and distribution
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Regulatory Agencies
• ATF – Bureau of Alcohol, Tobacco, and
Firearms
• BOP – State Boards of Pharmacy
• CMS – Centers for Medicare and Medicaid
Service
• DEA – Drug Enforcement Administration
• DOT – Department of Transportation
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Regulatory Agencies
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EPA – Environmental Protection Agency
FDA – Food and Drug Administration
The Joint Commission
NABP – National Association of the Boards
of Pharmacy
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Institutional Review Boards
• Designed to oversee biomedical and
behavioral research to protect the public
• Can approve or reject new research, or ask
for modifications to research
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