FDA - INTRODUCTION TO DRUG
REGULATION
Edward P. Richards
Director, Program in Law, Science, and
Public Health
Louisiana State University Law Center
http://biotech.law.lsu.edu
Basic Mission
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Safety
Efficacy
 Drugs
 Medical Devices
Truthful Labeling
 Adulteration
 Misbranding
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FDA's Structure and Organization
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The Commissioner
 President Appoints, Senate Confirms
 4th Tier in HHS
Not an Independent Agency
Insulation From Politics (Old Days)
 Few Political Appointees
 Scientific Basis of Its Decisions
 Visibility Protects It From Presidential Pressure 3
Does Congress Defer to the FDA?
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No, Congress Constantly Reviews the Agency in
Committee Meetings
Why?
 Lots of Money
 Lots of Powerful Interests
 Drugs, Food Labeling
 Food and Drug Cranks
4
Political Control - Food Supplements
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Did Regulate Food Supplements and “Health
Foods”
 Began to Crack Down on Unproven Claims and
Raise Questions about Safety
 Congress was Lobbied (Oren Hatch)
Pulled the FDA Authority to Regulate Food
Supplements
 Can Only Act on Evidence of Post-Marketing
Harm
 No Pre-Market Approval
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What Does the FDA Regulate?
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Food (with Agriculture Department)
Drugs
Biologics
Medical Devices
Cosmetics
Anything That Produces Dangerous Radiation
25% of the Consumer Dollar
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What Is a Drug? 201(g)
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(A) Articles Recognized in the Official United
States Pharmacopoeia, Official Homeopathic
Pharmacopoeia of the United States, or Official
National Formulary, or Any Supplement to Any of
Them
 Does the FDA Really Treat Every Thing in These
As Drugs?
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What Is a Drug? 201(g)
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(B) Articles Intended for Use in the Diagnosis, Cure,
Mitigation, Treatment, or Prevention of Disease in Man
or Other Animals
How Do You Judge This?
 Manufacturer or Seller's Representations
 Are These Limited to Labels and Advertising?
 No, Sec Info Is an Example
 Can Consider Consumer Expectations in Exceptional
Circumstances
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What Is a Drug? 201(g)
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(C) Articles (Other Than Food) Intended to Affect
the Structure or Any Function of the Body of Man
or Other Animals
 Do They Really Mean This? (Guns, Bullets)
(D) Articles Intended for Use As a Component of
Any Article Specified in Clauses (A), (B), or (C) of
This Paragraph.
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Prescription Drug Regulation
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Good Old Days
 In the Early 1900s You Could Get Anything You Wanted
 No Concern for People Poisoning Themselves
 Few Effective Drugs
 Limited Rationale for Physician Supervision
Harrison Narcotics Act
 Heroin Was the Hero Drug Because It Saved People
From Morphine
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Getting a Drug Approved
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Isolate or Synthesize the Agent
 Many are Biologicals
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Cyclosporin
Tamoxifen
Structure Activity Design
 Genetic Engineering
Do Animal or in Vitro Studies to Determine Activity
Apply for an Investigational New Drug (Ind) Permit
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Requirements for Approval for Sale in
Interstate Commerce
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Safe
 As compared to what?
 How is this relative to the underlying condition
being treated?
Effective
 How effective?
 Compared to placebo?
 Compared to other drugs?
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Submit for FDA Approval
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Clinical Trials Can Take Years
Very Expensive >>$200,000,000
Most Drugs are Not Approved
Labeling is Key to Approval
 Narrow Use allows More Dangerous Drugs
 Broader Use Means More Money
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Clinical Trials
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Phase I
 What are the side effects?
 Is it safe enough to test?
Phase II
 Does it work at all?
 What is the dosage range?
Phase III
 Is it better than placebo?
 Is it better than other treatments?
 What are the side-effects
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Conflicts in Clinical Trials
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Life Saving Drugs
 Patients want a cure
 Drugs probably do not work
 What if the drug is available outside the trial?
 Do you quit a drug that works to get on the trial?
 What if the patient Lies?
Non-Life Saving Drugs
 Pay the subjects?
Docs get paid by the patient
Companies want positive results
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The Drug Lag
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What Is the Drug Lag?
What Are the Conflicts?
FDA Risk Aversion?
Freedom of Choice?
What Are the Conflicting Expectations That the
FDA Faces?
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Sources of Law on Drug Labels
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Federal Trade Commission
FDA
State Deceptive Trade Practices Laws
State Tort Laws
No FDA preemption of state requirments
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Why Is Labeling So Important?
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All Drugs Pose Risks
 Inherent Risks
 Risks Due To Interactions With Other Drugs
 Risks Due To Disease States
 Risk Of Over and Under Dosage
NO RISKS ARE OBVIOUS!
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Manufacturers Have The Most Information
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Clinical Trials Under The IND
 Proprietary Information
 Controlled By The Manufacturer
 Should Be Reported To The FDA
Post-Market Information
 Manufacturer Gets Primary Reports
 Should Pass Information To The FDA
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What is a Label - I
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"Brochures, booklets, mailing pieces, detailing pieces,
file cards, bulletins, calendars, price lists, catalogs,
house organs, letters, motion picture films, film strips,
lantern slides, sound recordings, exhibits, literature, and
reprints and similar pieces of printed, audio or visual
matter descriptive of a drug and references published (for
example, the Physician's Desk Reference)
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What is a Label - II
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for use by medical practitioners, pharmacists, or
nurses, containing drug information supplied by
the manufacturer, packer, or distributor of the
drug and which are disseminated by or on behalf
of its manufacturer, packer, or distributor are
hereby determined to be labeling as defined in
section 201(m) of the FD&C Act."
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Rx Drugs
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Physician Information
 Package Insert
 Information Sheets For Physicians
Depends on Expertise of Physician
 What about non-physician prescribers?
Rarely, Patient Package Insert
 When Patients Have Significant Control Over Choice
of Drugs
 Birth Control Pills
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OTC
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On The Box
Insert In The Box
Must Allow Safe Use By Consumer
Labeling Issues Often Determine Whether A Drug
Is OTC or Rx
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Labels Can Make The Drug
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Apple Cider Vinegar Alone is not a Drug
 Apple Cider Vinegar with a Label that Says It
Will Cure Cancer is a Drug, Subject to FDA
Regulation
 Also Subject to FTC Regulation
Does a Book Saying it Treats Cancer Make it a
Drug?
Is the Author Guilty of Misrepresentation?
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FDA Standards for Labels
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A Drug is Misbranded If:
 [Its] "labeling is false or misleading in any
particular" or
 the labeling does not bear "adequate directions
for use."
Drugs are Misbranded if the Manufacturer Does
Not Use the FDA Approved Label Information
Misbranded Products Cannot Be Sold
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Federal Trade Commission Standards for
Labels
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Misleading Or Deceptive
FTC Looks At All Advertising And Promotional Materials
Penalties
 Civil Fines
 Criminal Prosecution
Usually Secondary To The FDA For Drugs
Governs Medical Products That Are Not Under the FDCA
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Tort Law Standards for Labels
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Must Provide Full Prescribing Information
Must Provide All Side-effects and
Contraindications
Must Anticipate Misuse and Warn Against it
Must Quickly Add Any New Information about the
Drug
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What the Label Cannot Have
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Unapproved Uses
 Only Uses From Approved NDAs
 Hence "Off-Label" Uses
Disputes with the FDA
No Over-Warning
 CYA in Tort Cases
 Interferes with Rational Prescribing
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Patient Package Inserts
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Legal Authority To Require?
Regulatory History
Why Did Physicians Oppose Them?
What Drugs Must Have Them Now?
Why Is The FDA Interested In Them Again?
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Promotional Materials
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Real Issues
 Off Label Uses
 Inappropriate Use
FDA Authority Over Promotional Materials
 Can The FDA Control What Detailmen Say?
 How Have Companies Gotten In Trouble?
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Providing Information On Unapproved
Uses
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The Manufacturer Cannot Advertise Unapproved Uses
The Manufacturer Can Send Out Medical Journal Reprints
On Unapproved Uses
 Must Log and Notify FDA
 May Have to Retract if the Science Changes
Must A Manufacturer Warn Against Known Unapproved
Uses?
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Requirements for Direct to Consumer Ads
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All the contraindications
All the warnings
All the major precautions
All other frequently occurring side effects that are
likely to be drug-related
Include Contact Phone and URL
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Internet Information
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WWW Pages are Subject To FDA Regulation
Non-Manufacturer Sites
 Can Pharmacies Tout Unapproved Uses?
 What about Access to Rx Drugs without an Rx?
Can Manufacturers Link To Non-Manufacturer
Sites?
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Direct to Patient Marketing and OTC
Switch
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Are the Vast Majority of People Prepared for Selfmedication?
 What Is the Products Liability Problem?
 Labels for Idiots
Social Policy for Communicable Diseases?
 Defeats the Reporting System
 Improper Antibiotics Use Leads to Drugresistant Infections
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Tort Implications of Direct Advertising
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Undermines Learned Intermediary Defense
Can Trigger a Duty to Warn the Patients Directly
 Makes Rx Drugs More Like OTC
 Must the FDA Approve a Voluntary PPI?
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Future Issue
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Commercial Speech Restrictions On FDA
Authority
Blurring of OTC And RX Labeling Because Of
Internet Sales
Shifting Of Warning Duties To Pharmicists
Changing Labeling Standards As States License
Non-Physician Prescribers
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Controlled Substances
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Drug Enforcement Administration (DEA)
What Are the 5 Schedules?
 I High Potential for Abuse and No Currently Accepted
Medical Use (in the Us) - Heroin
 II High Potential for Abuse but a Medical Use
 III Moderate Potential for Abuse
 IV Low Potential for Abuse
 V Lowest Potential for Abuse
Constitutional Right to Do Dope?
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Post-Market Surveillance - The Vioxx
Question
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Clinical Trials Are Limited in Time and Scope
 Many Serious Side-effects Cannot be Detected in
Trials
 Dangerous to Include Pregnant Women, so no
tetragons are detected
Docs are Supposed to Report Side-effects
 Not always very effective
Large Scale Trials Should Continue
 Who will fund them?
 Drug Companies do not want to undermine their
products
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History of Drug Liability
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FDA History is the History of Drug Injuries
FDA Regulation Tries to Prevent Future Injuries
Tort Litigation Compensates for Past Injuries
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Multiple Sovereigns
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Tort Law for Drugs is State Law
 Basic Theories are the Same
 Significant Variation on Details
 Federal Courts Apply State Law
Individual Judges Have Great Discretion
 Many Case Depend on Whether the Judge
Admits the Plaintiff's Evidence
 Forum Shopping
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Negligence
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Traditional Cases Were Usually Based in
Negligence
Had to Show Legal Relationship – Privity
 No Relationship Between Patient and Drug
Company
 Ended with Pharmacist
Made Sense when Pharmacists Compounded all
the Drugs
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Fall of Privity
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Courts Found Privity Out of Date with the
Industrial Revolution
Thomas v. Winchester (1852)
 Supplier Provided Belladonna rather than
Dandelion
 Privity would have Blocked the Claim
 Court Limited Privity for Dangerous Activities
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Early Strict Liability
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Many States Imposed Strict Liability for
Ultrahazardous Activities
 Blasting
 Impounding Water
Plaintiff did not need to Show Negligence, only
Injury Due to the Activity
Very Limited Application – not generally extended
to Drugs
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Limits of Negligence
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Must Show Breach of Standard of Care
 What a Reasonable Manufacturer Would Do?
 Only Evidence is Other Manufacturers
Must Show What Happened to the Specific Batch
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Warranty Theories
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Predate Strict Liability
Related to UCC Warranties
Cannot Disclaim for Personal Injuries
Based on Promises
Special Problem for Promoting Off-Label Uses
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Express Warranty
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Manufacturer Is Held to Specific Promises
Shatterproof Windshield Case
 Claimed It Was Just “Puffing”
 Court Said It Was a Clear Promise
 Did Not Matter If It Was Impossible
Can Be Written or Verbal
Can Physicians Give Binding Warranties About
Products?
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Implied Warranties
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Implied From the Context of the Sale
 A Product Is Safe for What It Is Sold for
 FDA Approved Drugs Have Only the Stated
Risks
Implied Warranty of Fitness for a Specific Purpose
 Manufacturer or Seller Says the Product Is
Good for Something Other Than Its Usual
Purpose
 Use of Drugs For Unapproved Purposes
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Jeep Case
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Jeep Sold for off the Road Use
 Rolled and Killed and Injured Passengers
 Made Like a Sardine Can
 Manufacturer Claimed Improper Use
How Do You Prove?
 Advertising
 Representations by Sales Persons
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Shift to Strict Liability
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Hard to Prove Negligence for Products
 Generic Goods - No Specific Information
 Defendant’s Have Lots of Resources
Defects Affect Lots of People
Strict Liability Encourages Safety
 Cannot Escape Liability by Just Doing What
Others Do
 Safer Products = Lower Costs
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