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
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
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
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
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
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?
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
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.
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
Getting a Drug Approved
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Isolate or Synthesize the Agent
 Many are Biologicals
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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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Cyclosporin
Tamoxifen
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
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
Submit for FDA Approval
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Clinical Trials Can Take Years
Very Expensive >>$100,000,000
Most Drugs are Not Approved
Labeling is Key to Approval
 Narrow Use allows More Dangerous Drugs
 Broader Use Means More Money
Modern Labeling
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Labeled for the Physician
 Physician Chooses the Drug
 Physician Is Assumed to Know Pharmacology
and Therapeutics
 Must Provide All Information About Side-effects
and Contraindications
Huge Issue When States Allow Non-physicians to
Prescribe Drugs
Labeling and Promotion
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Label Limited to Proven Efficacy
Until Recently, Promotions Limited to Proven
Efficacy
What Is the PDR?
 Private Listing of Drug Info and Promotions
 Info Provided in the PDR in a Label
 Must Be the Same As the Package Insert
“Off Label” Use
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Any Use That Is Not FDA Approved
Why Not Get Approval?
 Time
 Money
FDA Does Not Regulate Physicians
Many Common Uses Are off Label
Plaintiff’s Try to Make It Negligence
OTC Drugs
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Labeling Is the Key
 Directions for Safe Use
 Recognize Complications
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Recognize Contraindications
X-OTC Switch
Why?
 When?
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Self-treatment and Care?
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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
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?
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?
Post-Market Surveillance
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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