FDA - INTRODUCTION TO DRUG REGULATION

1. 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

2. Basic Mission • Safety • Efficacy • Drugs • Medical Devices • Truthful Labeling • Adulteration • Misbranding

3. FDA's Structure and Organization • 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

4. Does Congress Defer to the FDA? • No, Congress Constantly Reviews the Agency in Committee Meetings • Why? • Lots of Money • Lots of Powerful Interests • Drugs, Food Labeling • Food and Drug Cranks

5. What Does the FDA Regulate? • Food (with Agriculture Department) • Drugs • Biologics • Medical Devices • Cosmetics • Anything That Produces Dangerous Radiation • 25% of the Consumer Dollar

6. Food Supplements • 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

7. What Is a Drug? 201(g) • (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?

8. What Is a Drug? 201(g) • (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

9. What Is a Drug? 201(g) • (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.

10. Prescription Drug Regulation • 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

11. Getting a Drug Approved • Isolate or Synthesize the Agent • Many are Biologicals • Cyclosporin • Tamoxifen • Structure Activity Design • Genetic Engineering • Do Animal or in Vitro Studies to Determine Activity • Apply for an Investigational New Drug (Ind) Permit

12. Clinical Trials • 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

13. Conflicts in Clinical Trials • 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

14. Submit for FDA Approval • 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

15. Modern Labeling • 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

16. Labeling and Promotion • 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

17. “Off Label” Use • 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

18. OTC Drugs • Labeling Is the Key • Directions for Safe Use • Recognize Complications • Recognize Contraindications • X-OTC Switch • Why? • When?

19. Self-treatment and Care? • Are the Vast Majority of People Prepared for Self-medication? • What Is the Products Liability Problem? • Labels for Idiots • Social Policy for Communicable Diseases? • Defeats the Reporting System • Improper Antibiotics Use Leads to Drug-resistant Infections

20. Controlled Substances • 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?

21. The Drug Lag • What Is the Drug Lag? • What Are the Conflicts? • FDA Risk Aversion? • Freedom of Choice? • What Are the Conflicting Expectations That the FDA Faces?

22. Post-Market Surveillance • 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