It is not the critic who counts, not the man who points out how the strong man stumbled, or where the doer of deeds could have done better. The credit belongs to the man who is actually in the arena; whose face is marred by the dust and sweat and blood;

1
It is not the critic who counts, not the man who
points out how the strong man stumbled, or where
the doer of deeds could have done better. The
credit belongs to the man who is actually in the
arena whose face is marred by the dust and sweat
and blood who strives valiantly who errs and
comes short again and again who, at the best,
knows in the end the triumph of high achievement,
and who, if he fails, at least fails while daring
greatly so that his place shall never be with
those cold and timid souls who know neither
victory or defeat . . . .Theodore
RooseveltParis, The Sorbonne, 1910
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MEDICAL PRODUCT REGULATION

• Steven S. Kuwahara, Ph.D.
• GXP BioTechnology, LLC
• PMB 506, 1669-2 Hollenbeck Ave.
• Sunnyvale, CA 94087-5042
• Tel. FAX [phone]
• E-Mail stevekuwahara_at_yahoo.com

3
History of U.S. Food and Drug Law 1820.

• English Common Law 1202 King John proclaims the
  Assize of Bread.
• Prohibits adulteration of bread with ground peas
  or beans.
• Napoleonic Code 1804.
• Producers of beverages must declare the contents
  of the beverages.
• Results in makers of eau de toilette declaring
  them to be scents and eventually called
  Colognes.

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History of U.S. Food and Drug Law 1820.

• Early emphasis was on Food
• Not many real drugs at this time.
• 1820 11 physicians meet in Washington, D.C. and
  establish the U.S. Pharmacopeia.
• Compendium, but no legal status.
• Legal status comes later with recognition by
  congress as a source of pharmaceutical standards.

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History of U.S. Food and Drug Law 1848.

• 1848 Drug Importation Act requires inspection by
  U.S. Customs Service.
• Prevents importation of adulterated drugs.
• U.S. was like a third world country. All kinds of
  ineffective nostrums and adulterated preparations
  were being imported.
• 1862 Lincoln forms the U.S. Department of
  Agriculture and appoints a chemist as head of the
  Bureau of Chemistry.

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History of U.S. Food and Drug Law 1880.

• 1880 Chief Chemist of USDA recommends passage of
  national Food and Drug law based on his
  investigations.
• The bill is defeated. In the next 25 years 100
  more bills will be introduced and defeated.
• 1883 Harvey Wiley (chemist and M.D.) is
  appointed as head of the Bureau of Chemistry. He
  will be known as the Crusading Chemist and
  Father of the Pure Food and Drugs Act.

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History of U.S. Food and Drug Law 1898.

• 1898 Association of Official Agricultural
  Chemists (Now AOAC International) Forms a
  committee on Food Standards headed by Dr. Wiley.
• 1902 Biologics Control Act is passed to control
  purity and safety of serums, vaccines etc. Leads
  to the precursor of the Center for Biologics
  Evaluation and Research (CBER).
• 1902 Congress gives 5,000 to the Bureau of
  Chemistry to study preservatives and colors.

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History of U.S. Food and Drug Law 1906.

• 1906 With the strong support of Theodore
  Roosevelt, the Food and Drugs Act is passed on
  the same day as the Meat Inspection Act.
• The act prohibits interstate commerce in
  misbranded or adulterated foods, drinks and
  drugs.
• Meat becomes a special class of food and will be
  regulated by the USDA.
• Result of unsanitary conditions, use of poisonous
  additives, cure-all claims for ineffective or
  dangerous patent medicines.

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History of U.S. Food and Drug Law 1900.

• At this time the prevailing philosophy was that
  the public should be told what ingredients were
  present and should make up their own minds
  about the utility of a drug or the danger of a
  food.
• 1911 U.S. v Johnson ruled that the Food and Drug
  Act did not prohibit false therapeutic claims
  only false claims about ingredients or identity.

10
History of U.S. Food and Drug Law 1912 27.

• 1912 Congress passes the Sherley Amendment.
• Prohibits labeling with false therapeutic claims
  intended to defraud the purchaser.
• Manufacturer is innocent if he can claim a lack
  of intent to defraud.
• 1927 Food, Drug, and Insecticide Administration
  is formed within the Bureau of Chemistry.

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History of U.S. Food and Drug Law 1930 33.

• 1930 Name is changed to the Food and Drug
  Administration (still within the USDA).
• 1933 FDA recommends a revision of the 1906 Food
  and Drugs Act.
• Bill is introduced into the Senate and a
  five-year legislative battle begins.
• Deaths and a scandal will be needed to pass it.

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History of U.S. Food and Drug Law 1937.

• 1937 Elixir of Sulfanilamide kills 107 people
  (many children) because the solvent (glycerin) is
  heavily contaminated with diethylene glycol.
• Prosecution is successful only because the term
  elixir required the use of ethyl alcohol.
  Product was therefore misbranded and a recall was
  possible.
• 60 years later an almost identical event will
  kill 87 children in Haiti. Acetaminophen was the
  active ingredient.

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History of U.S. Food and Drug Law 1938a.

• 1938 Food, Drug, and Cosmetic Act (FDCA) is
  passed.
• Extends control to cosmetics and therapeutic
  devices.
• Requires that new drugs be shown to be safe
  before marketing.
• Eliminates requirement to prove intent to defraud
  in drug misbranding.
• Adds court injunctions to previous seizures and
  prosecutions as penalties.

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History of U.S. Food and Drug Law 1938b.

• Wheeler-Lea Act The Federal Trade Commission
  (FTC) is charged with regulating advertising of
  FDA products with the exception of prescription
  drugs. This situation still exists.
• 1940 FDA is transferred from the USDA to the
  Federal Security Agency. First commissioner named.

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History of U.S. Food and Drug Law 1943.

• U.S. v Dotterweich Supreme court rules that
  responsible officials and the corporation itself
  may be prosecuted for violations.
• It need not be proven that the officials intended
  or even knew, of the violations.
• 1944 Public Health Service Act covers regulation
  of biologics and control of communicable
  diseases.
• Places biologics under the Public Health Service.

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History of U.S. Food and Drug Law 1949.

• First FDA Guidance to Industry known as the
  Black Book.
• Title was Procedures for the Appraisal of
  Toxicity of Chemicals in Food.
• 1950 Alberty Foods Products v U.S. Court rules
  that directions for use on a drug label must
  include the purpose for which the drug is
  offered. Therefore a worthless remedy cannot
  escape the law by not stating the condition it is
  supposed to treat.

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History of U.S. Food and Drug Law 1951.

• Durham-Humphrey Amendment Defined the kinds of
  drugs that require medical supervision and
  restricted their sale to prescription.
• 1953 Federal Security Agency becomes the
  Department of Health, Education and Welfare
  (DHEW).
• 1953 Factory Inspection Amendment clarifies
  previous rules and requires inspectors to provide
  written reports of inspection observations.

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History of U.S. Food and Drug Law 1955.

• NIH biologics control function becomes the
  Division of Biologics Control.
• This is after a scandal where 260 cases of polio
  result from the release of a vaccine that was
  supposed have been inactivated.
• (Inactivation method was ineffective due to
  process error. Laboratory testing did not detect
  this, and permission to release was given.)

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History of U.S. Food and Drug Law 1960.

• Color Additive Amendment Requires manufacturers
  to establish safety of color additives in foods,
  drugs, and cosmetics. Delaney clause prevents use
  of any color additive shown to cause cancer in
  humans or animals.
• 1962 Consumer Bill of Rights proclaimed by John
  F. Kennedy in message to congress. Includes
  right to safety, to be informed, to choose, and
  right to be heard.

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History of U.S. Food and Drug Law 1962.

• Kefauver-Harris Drug Amendments
• Requires that manufacturer prove that drugs are
  efficacious before marketing them.
• Previous requirement was only for safety.
• 1966 Initiates an NAS/NRC contract to study
  efficacy of 4,000 drugs approved between 1938 and
  1962.
• These will be known as DESI products.

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History of U.S. Food and Drug Law 1966.

• Fair Packaging and Labeling Act.
• All consumer products in interstate commerce must
  be honestly and informatively labeled.
• FDA enforces provisions on foods, drugs,
  cosmetics and medical devices. Note This covers
  labeling, not advertising.
• 1968 FDA Bureau of Drug Abuse Control is
  combined with Treasury Dept. Bureau of Narcotics
  to form Bureau of Narcotics and Dangerous Drugs
  (BNDD) in the Justice Dept.

22
History of U.S. Food and Drug Law 1968.

• FDA is placed in the Public Health Service along
  with CDC NIH.
• Drug Efficacy Study Implementation (DESI)
  implements recommendations of NAS/NRC efficacy
  studies.
• Animal Drug Amendments place new animal drugs and
  medicated feeds under FDA.
• EPA established and takes over FDA pesticide
  tolerance program.

23
History of U.S. Food and Drug Law 1970.

• Upjohn v. Finch Court rules that commercial
  success alone does not constitute substantial
  evidence of safety and efficacy.
• 1972 Review of over-the counter (OTC) drugs to
  determine safety, efficacy, and appropriate
  labeling.
• 1972 Regulation of biologics transferred from
  NIH to FDA. DBS becomes BoB.

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History of U.S. Food and Drug Law 1976.

• Medical Device Amendments passed to cover safety
  and efficacy of devices and includes diagnostic
  products. Registration with FDA now required and
  GMPs must be followed.
• Vitamins and Minerals Amendments (Proxmire
  amendments) stop FDA from establishing standards
  limiting the potency of vitamins and minerals in
  food supplements or regulating them as drugs
  based on their potency.

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History of U.S. Food and Drug Law 1977.

• Saccharin Study and Labeling Act.
• Prevents FDA from banning it but requires label
  about carcinogenicity.
• 1980 Infant Formula Act. FDA controls on
  nutrition and safety.
• 1982 Tamper-Resistant Packaging Regulations
  issued by FDA as GMP.
• 1983 Orphan Drug Act. Promotes research and
  marketing.

26
History of U.S. Food and Drug Law 1984.

• Fines Enhancement Laws Increase penalties for
  all federal offenses.
• 100K for individuals, 250K for felonies or if
  violation causes death. Amounts are doubled for
  corporations.
• Drug Price Competition and Patent Term
  Restoration Act.
• Generics can be marketed without repeating full
  safety and efficacy studies
• Brand-names can receive additional 5 yr of patent
  coverage to make up for delays due to approval
  process.

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History of U.S. Food and Drug Law 1988.

• Food and Drug Administration Act.
• Places FDA in the Department of Health and Human
  Services (DHHS) with a commissioner appointed by
  the President with advice and consent of the
  Senate.
• 1990 Safe Medical Devices Act (SMDA). Requires
  post approval monitoring of medical devices and
  permits FDA to order the recall of medical
  devices.

28
History of U.S. Food and Drug Law 1992.

• Prescription Drug User Fee Act (PDUFA) requires
  fees for drug and biologics submissions and
  services.
• 1994 Dietary Supplement Health and Education
  Act.
• Established a regulatory framework and authorized
  FDA to develop GMPs. Defines nutraceuticals as
  foods.

29
History of U.S. Food and Drug Law 1997.

• Food and Drug Administration Modernization Act
  (FDAMA)
• Accelerates review of devices.
• Short cuts GMPs in some cases.
• Regulates advertising of unapproved uses of
  approved drugs and devices (off label uses).
• Regulates health claims for foods.
• Mainly by defining meanings and restricting
  wording.

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Cultivate the habit of attention and try to gain
opportunities to hear wise men and women talk.
Indifference and inattention are the two most
dangerous monsters that youll ever meet.
Interest and attention will ensure to you an
education.

• Robert Millikan