Food and Drug Law Fall 2010

1. Food and Drug LawFall 2010 Ralph F. Hall September 7, 2010

2. U.S. v. French Bronze Tablets888 F2d 945 (2d. Cir. 1989) “We now commence our tortuous journey through the Food, Drug and Cosmetic Act.” “[W]e are mindful of Learned Hand’s consoling words on his foray through the Internal Revenue Act: ‘cross-reference to cross-reference, exception upon exception – couched in abstract terms … successfully concealed …which it is my duty to extract, but … only after the most inordinate expenditure of time.”

3. Happy Birthday!!!(a bit belated)

4. FDA Centennial Anthem

5. FDA Overview • Regulates 25-30% of U.S. Economy • Old line administrative agency • One of the first consumer protection agencies • Helped develop administrative law • Mixes law, public policy, science, medicine and politics • Long institutional memory impacts decisions • Thalidomide and Dr. Kelsey • Poison Squad • Generic drug scandal

6. Why Study the FDA • Broad, cross disciplinary skills • Classic administrative agency • Transferable skills • Oldest existing consumer protection agency • Processes and structure used in other agencies • Develop analytical skills in complex area • Subject specific factors • FDA has a key impact on daily life • Cutting edge issues • Life sciences are in a state of revolutionary development • Involved in major policy debates • If FDA or regulated industry make a mistake people die • Huge economic impacts

7. “Somebody has to do something and it’s just incredibly pathetic that it has to be us” - Jerry Garcia The Grateful Dead

8. The Challenge of FDA Law

9. FDA Law • FDA law and logic can seem bizarre • What is a maggot? • What is mouthwash? • Cosmetic • Drug • Device • What is the difference between a frozen cheese pizza and a frozen pepperoni pizza? • What happens if I put a sealed top on the water I sell? • Circular definitions

10. FDA Law • Definition of “food” • “The term ‘food’ means 1) articles used for food or drink for man or other animals, 2) chewing gum …” 21 USC § 321(f)

11. Policy Issues • Imagine you have been diagnosed with terminal cancer. Existing FDA approved therapies are ineffective. A new drug is in FDA regulated clinical trials. This drug is your only hope. • You don’t qualify for the clinical trial. • Do you have a right to try the new therapy? • Assume full disclosure of risks • It’s your life

12. Tools for Regulation • Food Drug and Cosmetic Act • Related regulations and guidance documents • Enforcement actions and court decisions • Ancillary laws and regulatory systems • Office of Inspector General (OIG) • Federal Trade Commission (FTC) • Securities and Exchange Commission (SEC) • General civil and criminal laws • Product recalls • Public opinion

13. Policy and Economic issues Year Cost per NCE Total R&D # of NCEs 1990 $445 MM $16 BB 23 1996 $608 MM $29 BB 53 2000 $802 MM $44 BB 27 2005 $1.7 BB $68 BB 20 2006 $1.8 BB (est) $70 BB (est) 18 2008 ? ? 22

14. Policy and Economic issues • High cost of drugs • 10 years and $1.5 BB • 5-10 years of patent protection • Investment return • $125 MM (time value at 7%) • $180-360 MM per year for principle • Assuming 40% margin • Company must sell $800 MM + per year • If 20,000 patients, cost per patient = $40,000

15. Course Overview

16. Course overview • Class process • Text • Supplemental material • Statutes • Regulations • Guidance documents • Glossary & acronyms • Class lecture and participation • Attendance • Final exam

17. Class Process • Reading assignments • Hutt, Merrill & Grossman • Often more of a thesis • READ the related statutes • Current events • Class lecture & discussion • Horizontal, cross functional approach • Occasional “deep dives” • Final Exam

18. Course Objectives • Substantive knowledge • Jurisdictional issues • Core regulatory processes and concepts • Adulteration • Misbranding • Policy challenges • Administrative process • Enforcement • Regulatory development • “Real life” as an FDA/administrative lawyer

19. Course Objectives • Identification and analysis of current major issues • Abigail Alliance • 1st Amendment and off-label promotion • Cost/benefit issues • Product approval issues • Comparative effectiveness • Food safety • 510(k) reform • Understand interface between law, health policy, medical care and economics

20. My Background • Several decades in-house counsel • Eli Lilly • Guidant Corp. • Retired 2003 • Senior VP and Deputy General Counsel • GC of division with over $1 BB in sales • Academic role • Of counsel to Baker & Daniels (Indianapolis) • CEO – MR3 Medical LLC • Start up device company

21. Key Success Attributes

22. Overview of the FDA

23. FDA Scope and Jurisdiction

24. Health Care Policy Makers • Congress • Executive branch (White House, HHS, etc.) • FDA • What therapies are available • Cost profile • New drug costs $800 MM - $1.5 BB • Safety and efficacy • Physicians and physician groups • Payors • CMS • Payment, coverage, “rationing” • Private carriers • Patients and advocacy groups

25. Health Care Policy • FDA gets involved (dragged?) into many political and policy debates • Life style issues (tobacco, obesity) • 1st Amendment rights (promotion restrictions) • Abortion rights (RU 486, Plan B) • Personal choice (dietary supplements) • Right to treatment (access to unapproved products - AIDS and cancer therapies) • Health care cost (Drug importation) • Economic fraud (laetrile) • Product liability (Vioxx and preemption)

26. FDA BalancesCompetingPolicies Innovation Certainty Access Final Policy Safety Controls FDA These Polices are often Inconsistent Risk Elimination Cost Therapy Needs Personal Choice

27. Recent High Profile Events • Plan B • Tobacco • Vioxx • Allegations of lax approval and surveillance • Flu vaccine • Access to therapies (including cost issues) • Product issues and recalls • Food (spinach, lettuce, meat recalls) • Drugs (Avandia, Vytorin, Zetia) and devices (ICDs) • Food safety • Bioterrorism • Product liability (Reigel, Wyeth) • 510(k) reform

28. FDA Mission Statement • The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

29. FDA Mission§393(b) • [P]romote public health by promptly reviewing clinical research and marketing applications • ensure that • foods are safe • drugs are safe and effective • reasonable assurance that devices are safe and effective • global regulatory harmonization • consultation with experts, consumers, manufacturers, etc.

30. FDA Mission • Advance public health • Role of life style choices • Safety of all regulated products • Efficacy of certain products • “Speed innovation” • Affordability of products • Information source • Are these consistent?

31. Major FDA Policy Debates • Assist with approvals or act in a command/control fashion • Encourage new therapies • new developments include risk • the known is less risky • Information v. control • Who decides, the individual or FDA • Determine risk/benefit ratio • Penicillin v. Rogaine • Local v. national v. global control

32. Key Reminders • FDA does not regulate the practice of medicine • The source of FDA’s authority is interstate commerce • Broad definition • Definitions are key • Jurisdiction • Regulatory structure • Obscure definitions and regulations are often the key • Other agencies have related authority • USDA – meat, eggs, etc. • CMS • FTC • EPA

33. What is FDA? • Science based decision maker • Role of Science • Decisions based on science • Policy maker • Risk/benefit decisions • Science as just a part of decision making • Information agency • Consumer/patient autonomy • Enforcement agency • Adulteration and misbranding prohibitions • Promoter of innovation

34. FDA Structure • Part of HHS • Led by Commissioner • Congressional approval • Three key subparts • Program offices (Centers) • Field offices • General and administrative • Chief Counsel’s office • Policy and legislative activity • International • HR, finance, IT, etc.

35. FDA Structure

38. Center for Devices and Radiological Health (CDRH) Clinical trials Approvals Enforcement Product Surveillance

39. Efficient, Effective, and Predictable Product Development Total Product Life Cycle Ensuring the Safety of Marketed Medical Devices Enabling Technology and Innovation

40. Development of the FDCA and FDA

41. Development of FDA Law • FDCA amended hundreds of times since 1906 • FDAAA – 2007 • Tobacco - 2009 • Two key drivers for new FDA laws • Health crisis • Political pressures • Major statutory developments have been crisis driven • Congress and FDA often reactive • Rise of consumerism • Role of stakeholders • Industry • “Public interest” groups • Issue specific advocacy groups

42. Development of FDA Law • FDA regulatory systems have followed key social, political and scientific movements • Urbanization • Industrialization • Explosion in health care capabilities • Health and life expectations • Longer life spans • Life style choices • New technologies • Computers and information technology • Globalization • Patient control • Health care cost

43. Development of FDA Law • 1906 • Events: “The Jungle”, industrialization, public outcry and public health movement • Reaction: Creation of the modern FDA and passage of the FDCA • Key concepts: Prohibits adulteration (safety) Prohibits misbranding (fraud) Food focus

44. Development of FDA Law • 1938 • Event: Death of 100+ adults and children due to elixer of sulfanilimide w/ diethyleneglycol • Enforcement action based on “elixir” definition • Reaction: Creation of premarket approval requirements for drug safety • Key concept: drugs had to establish safety, premarket approval process

45. Development of FDA Law • 1962 • Event: Thousands of birth defects due to thalidomide; product not approved in US • Reaction: Passage of 1962 amendments relating to drug approval and safety • Key concepts: drug must demonstrate safety and effectiveness; New Drug Application process enhanced • Issues: “old” drugs and GRAS • Major cultural event for FDA (Dr. Kelsey)

46. Development of FDA Law • 1976 • Event: rise of complexity and use of medical devices (pacemakers, MRIs, orthopedics) • Dalkon shield, Shiley heart valve issues • Reaction: Regulate medical devices • Key concepts: premarket approval for medical devices; safety and effectiveness • Issues: “old” devices, low risk devices and “me too” devices

47. Development of FDA Law • 1980s • Event: human subject research • Reaction: Regulations protecting human subjects • Event: health care cost, fewer new products and generics • Reaction: Generic drug approval legislation and patent term restoration • Event: AIDS, cancer and access to therapy • Reaction: expanded access to investigational therapies

48. Development of FDA Law • 1980s • Event: Tylenol tampering • Reaction: Tamper resistant packaging laws and regulations • Event: Rare disorder awareness • Reaction: Orphan Drug Act • Event: Lack of agency resources and delays in drug approvals • Reaction: User fees, increased enforcement

49. Development of FDA Law • 1990s • Event: consumer awareness about food • Reaction: Nutrional Labeling and Education Act (NLEA) • Event: Popularity of health food and supplements • Reaction: Dietary Supplement Health and Education Act (DSHEA) • Event: Pressure for regulatory reform, need for resources and speed • Reaction: FDAMA and device user fees

50. Development of FDA Law • 2000s • Event: 9/11 • Reaction: Bioterrorism initiatives • New technologies • Nanotechnology, stem cells, etc. • Recalls and product issues (Vioxx) • FDAAA • Tobacco • Open issues: • Gene therapy • Dietary supplements • 1st amendment • Cost • Safety (particularly with “lifestyle” drugs)