Federal Food, Drug and Cosmetic Act of 1938

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Federal Food, Drug and Cosmetic Act of 1938

• Example of Administrative Government
• Enabling document.
• Agencies have three basic functions
• rule making authority -- very analogous to
  statutes passed by the legislatures.
• investigative or enforcement authority - an
  executive kind of power.
• dispute-resolution, or judicial authority.
• Right to judicial review of agency determinations
  via Constitution.

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Historical Perspective

• The Food, Drug, and Cosmetic Act
• Born of public health calamities and disasters.
• Original Food and Drug Act of 1906.
• no requirement to disclose ingredients.
• A largely unregulated industry was causing
  numerous public health problems.

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1906 Food and Drug Act of Congress

• prohibited sale of adulterated and misbranded
  drugs in interstate commerce.
• US v Johnson case
• The act did not prohibit false therapeutic
  claims, only false claims about ingredients.
• Sherley Amendment - 1912
• specifically prohibits false claims.

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1937 sulfanilamide crisis

• (ethylene glycol / propylene glycol mix-up)
• Congress passed the FDC Act in 1938
• products must be safe (or non-toxic).
• labeling defined written, printed or graphic
  matter accompanying the product.

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1951 - The Durham-Humphrey Amendments.

• How were pharmacists to make consistent
  determinations about which drugs could be given
  adequate directions on the label?
• The DH amendments gave FDA the responsibility to
  clarify which drugs are
• Habit-forming,
• Not safe except under a practitioners
  supervision, and,
• Drugs limited to prescription sale as part of the
  approval of a New Drug Application.
• Required Caution Federal Law Prohibits
  Dispensing Without a Prescription. (Today Rx
  Only.)
• Prescription exemption (for manufacturers)
• Pharmacists must label prior to dispensing.

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DH Amendments also established

• process for receiving, recording, and dispensing
  oral telephone prescriptions,
• the refill process, and
• minimum information for prescription labels.

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Late 1950s thalidomide crisis.

• Congress improved the NDA process to enhance the
  safety of medications.

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The Drug Amendments of 1962 (Kefauver-Harris)

• enhanced the pre-marketing testing requirements,
• mandated standard Good Manufacturing Practices,
  
• broadened the role of FDA,
• regulated advertising, and
• required informed consent in the clinical testing
  process.
• Kefauver-Harris imposed the efficacy requirement
  prior to NDA approval by FDA.

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1983 - Orphan Drug Act

• For diseases involving fewer than 200,000
  persons.
• The drugs often had no patent protection
• could not be profitably sponsored for such a
  limited market.
• market exclusivity (like a patent) and tax breaks
  to stimulate activity

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1984 - Drug Price Competition and Patent Term
Restoration Act

• a.k.a. Waxman-Hatch
• generic companies got clearer path to approval of
  their products
• brand-name companies got patent extensions for
  medications with lengthy NDA approval process
  times and for some pediatric medications.

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1987 - Prescription Drug Marketing Act

• The PDMA banned
• diversion of prescription drugs outside of
  legitimate commercial channels.
• re-importation of prescription medication (with
  minor exceptions),
• the trafficking (sale, trade, and purchase) of
  samples, and
• all but limited re-sales by hospitals and
  health-care entities.

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1992 - Prescription Drug User Fee Act (PDUFA)

• added to promote the prompt approval of safe and
  effective new drugs.
• allows payment of a user fee to expedite review
  of an NDA.

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1997 - Food and Drug Administration Modernization
Act (FDAMA).

• process for dissemination of off-label
  information (indications that are not approved by
  manufacturers).
• federal legend shortened to Rx only.
• provided for additional patent protection RE
  particular pediatric clinical assessments
• fast-track review
• life-threatening conditions or unmet medical
  needs.

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FDAMA distinguished compounding from manufacturing

• exempted traditional compounding practice from
  characterization of products as new drugs and
  the CGMP requirements as long as certain
  conditions are met.
• Thompson v Western States Medical Center
• cannot prohibit advertising under the First
  Amendment.
• protected commercial speech
• entire compounding aspect of FDA was
  unenforceable ? re-instituted a compliance
  policy guide discussing compounding.

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FDA compounding considerations

• Compounding drugs in anticipation of receiving
  prescriptions.
• Compounding unsafe drugs removed from market.
• Compounding finished drugs from bulk active
  ingredients not FDA approved.
• Receiving, storing, or using drug substances
  without proper assurances.
• Receiving, storing, or using drug components that
  do not meet official compendia requirements.
• Using commercial scale manufacturing or testing
  equipment.
• Compounding drugs for resale or wholesaling.
• Compounding commercially available products or
  virtual copies of same.
• Failing to comply with applicable state pharmacy
  practice law.

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Important Definitions

• See also www.fda.gov/opacom/laws/fdcact/fdcact1.h
  tm.
• All labeling is considered misbranded if it is
  not truthful or is misleading.
• this provision (along with adulteration) has its
  roots in the 1906 Food and Drug Act

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Important Misbranding Issues

• missing poison prevention or tamper-resistant
  packaging
• OTC products w/o adequate directions for use or
  prescription package w/o adequate information
  for use are misbranded.

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Example

• Suppose a prescription for amoxicillin 250mg was
  filled with amoxicillin 500mg and labeled as if
  dispensed correctly (Amoxicillin 250mg).
• Obviously the product is misbranded under the
  law.
• Prosecutions are rare, but possible.
• Note that the product is also adulterated (a
  frequent MPJE question).

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Dietary Supplements

• 1994 - Dietary Supplement and Health Education
  Act
• treats products more like foods for regulatory
  purposes
• prohibits regulation by FDA unless proof that the
  product is unsafe.
• Compare to NDA process
• NDA requires the manufacturer to prove safety and
  efficacy.
• DSHEA shifts the burden of proof from the
  manufacturer to FDA.
• New dietary supplements may be placed on the
  market within 30 days

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Types of Supplements

• A vitamin
• A mineral
• An herb or other botanical
• An amino acid
• A dietary substance for use by man to supplement
  the diet by increasing the total dietary intake
  or
• A concentrate, metabolite, constituent, extract,
  or combination of any ingredient described in
  clause (A), (B), (C), (D), or (E)

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Supplements (cont.)

• Note the distinction between treatment of
  disease and structure/function
• claims to effectively treat high blood pressure
  are therapeutic
• claims to lower blood pressure - not intended
  to diagnose, treat, cure, or prevent disease.
• DSHEA specifically exempts dietary supplements
  from drug status and therefore FDA regulation.
• State law conflict problems (even when state law
  was stricter)

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New Drug Approval Process

• See the FDAs website
• www.fda.cov/cder/learn/CDERLearn/default.htm
• Prohibited Acts
• placing an unapproved new drug in interstate
  commerce,
• adulteration, and
• misbranding.

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Administrative Enforcement Tools of the FDA

• power to grant and review licenses and to approve
  manufacturing
• FDA Rulemaking power
• FDA civil enforcement authority.
• injunctions,
• seizures,
• fines.
• complaint filed, with a subsequent hearing
• Criminal prosecution of intentional violations
  rare yet powerful penalty.

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Voluntary Recalls

• Class I strong likelihood ofadverse
  consequences or death,
• Class II temporary orreversible adverse health
  consequences,
• Class III not likely to cause adverse health
  consequences.
• Also a simpler market withdrawal if the risks
  are minor.
• hybrid action by the FDA is the Warning
  Letter.

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Drug Product Identification Tools

• National Drug Code (NDC) number
• labeler code,
• drug product code,
• package code
• Unique imprint code for oral solids.
• Required by 21 CFR 206
• allows identification of medications removed from
  their original package.
• Many states, including Wyoming, outlaw
  manufacture of non-imprinted products.

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Package Safety Issues

• Poison Prevention Packaging Act (PPPA)
• not part of the Food, Drug, and Cosmetic Act.
• administered by the Consumer Product Safety
  Commission (CPSC).
• packaging that is significantly difficult for
  children under 5 years of age to open.
• Few exceptions exist, but must be known. (see
  appendix)

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Package Safety 2

• Some OTC and other household items must comply
• acetaminophen,
• aspirin (w/ exceptions),
• iron-containing products,
• ibuprofen,
• diphenhydramine
• methanol, ethylene glycol, turpentine, lighter
  fluids, KOH, NaOH, and furniture polish.

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Anti-Tampering Amendment to the FDC Act

• often confused with the PPPA.
• Passed in 1982 in response to the Tylenol scare.
• Certain products not offered in tamper-evident
  packaging or properly labeled are considered
  adulterated or misbranded
• Also, any two-piece, hard gelatin capsule must be
  sealed using an acceptable tamper-evident
  technology.

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Drug Product Problem Reporting

• Med-Watch program
• FDA hotline for intervention when necessary
• Database of information from voluntary reporting
  by health care practitioners.
• things to be reported
• problems with the quality of drug products
  including the packaging
• adverse drug reactions (ADR) and medication
  errors (ME).
• (800-FDA-1088)
• www.fda.gov/medwatch/index.html
• fax transmission
• still a voluntary procedure.