FDA INTRODUCTION TO DRUG REGULATION Edward P Richards

FDA - INTRODUCTION TO DRUG REGULATION Edward P. Richards Director, Program in Law, Science, and Public Health Louisiana State University Law Center

Basic Mission n Safety Efficacy n Drugs n Medical Devices Truthful Labeling n Adulteration n Misbranding

FDA's Structure and Organization n The Commissioner n President Appoints, Senate Confirms n 4 th Tier in HHS Not an Independent Agency Insulation From Politics (Old Days) n Few Political Appointees n Scientific Basis of Its Decisions n Visibility Protects It From Presidential

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

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

Food Supplements n n Did Regulate Food Supplements and “Health Foods” n Began to Crack Down on Unproven Claims and Raise Questions about Safety n Congress was Lobbied (Oren Hatch) Pulled the FDA Authority to Regulate Food Supplements n Can Only Act on Evidence of Post. Marketing Harm n No Pre-Market Approval

What Is a Drug? 201(g) n (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 n Does the FDA Really Treat Every Thing in These As Drugs?

What Is a Drug? 201(g) n n (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? n Manufacturer or Seller's Representations n Are These Limited to Labels and Advertising? n No, Sec Info Is an Example n Can Consider Consumer Expectations in Exceptional Circumstances

What Is a Drug? 201(g) n n (C) Articles (Other Than Food) Intended to Affect the Structure or Any Function of the Body of Man or Other Animals n 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 n n Good Old Days n In the Early 1900 s You Could Get Anything You Wanted n No Concern for People Poisoning Themselves n Few Effective Drugs n Limited Rationale for Physician Supervision Harrison Narcotics Act n Heroin Was the Hero Drug Because It Saved People From Morphine

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

Clinical Trials n n n Phase I n What are the side effects? n Is it safe enough to test? Phase II n Does it work at all? n What is the dosage range? Phase III n Is it better than placebo? n Is it better than other treatments? n What are the side-effects

Conflicts in Clinical Trials n n Life Saving Drugs n Patients want a cure n Drugs probably do not work n What if the drug is available outside the trial? n Do you quit a drug that works to get on the trial? n What if the patient Lies? Non-Life Saving Drugs n Pay the subjects?

Submit for FDA Approval n n Clinical Trials Can Take Years Very Expensive >>$100, 000 Most Drugs are Not Approved Labeling is Key to Approval n Narrow Use allows More Dangerous Drugs n Broader Use Means More Money

Modern Labeling n n Labeled for the Physician n Physician Chooses the Drug n Physician Is Assumed to Know Pharmacology and Therapeutics n Must Provide All Information About Side-effects and Contraindications Huge Issue When States Allow Nonphysicians to Prescribe Drugs

Labeling and Promotion n Label Limited to Proven Efficacy Until Recently, Promotions Limited to Proven Efficacy What Is the PDR? n Private Listing of Drug Info and Promotions n Info Provided in the PDR in a Label n Must Be the Same As the Package

“Off Label” Use n n n Any Use That Is Not FDA Approved Why Not Get Approval? n Time n Money FDA Does Not Regulate Physicians Many Common Uses Are off Label Plaintiff’s Try to Make It Negligence

OTC Drugs n Labeling Is the Key n Directions for Safe Use n Recognize Complications n n Recognize Contraindications X-OTC Switch Why? n When? n

Self-treatment and Care? n n Are the Vast Majority of People Prepared for Self-medication? n What Is the Products Liability Problem? n Labels for Idiots Social Policy for Communicable Diseases? n Defeats the Reporting System

Controlled Substances n n n Drug Enforcement Administration (DEA) What Are the 5 Schedules? n I High Potential for Abuse and No Currently Accepted Medical Use (in the Us) - Heroin n II High Potential for Abuse but a Medical Use n III Moderate Potential for Abuse n IV Low Potential for Abuse n V Lowest Potential for Abuse Constitutional Right to Do Dope?

The Drug Lag n n n 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 n n n Clinical Trials Are Limited in Time and Scope n Many Serious Side-effects Cannot be Detected in Trials n Dangerous to Include Pregnant Women, so no tetragons are detected Docs are Supposed to Report Side-effects n Not always very effective Large Scale Trials Should Continue n Who will fund them? n Drug Companies do not want to undermine their products