1. Regulation of Labeling and Promotion Edward P. Richards Harvey A. Peltier Professor of Law Louisiana State University School of Law richards@lsu.edu http://biotech.law.lsu.edu Click Here For Updated Slides

2. 2 Sources of Law Federal Trade Commission FDA State Deceptive Trade Practices Laws State Tort Laws

3. 3 Legal Risks Drug Cannot Be Marketed Drug Can Be Removed From The Market Civil Fines Criminal Prosecution Tort Judgments Bankruptcy

4. 4 Why Is Labeling So Important? 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!

5. 5 Manufacturers Have The Most Information 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

6. 6 What is a Label - I "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)

7. 7 What is a Label - II 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."

8. 8 Rx Drugs Physician Information Package Insert Information Sheets For Physicians Depends on Expertise of Physician Rarely, Patient Package Insert When Patients Have Significant Control Over Choice of Drugs Birth Control Pills

9. 9 OTC On The Box Insert In The Box Must Allow Safe Use By Consumer Labeling Issues Often Determine Whether A Drug Is OTC or Rx

10. 10 Labels Can Make The Drug 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?

11. 11 Product Independent Labels Pamphlets And Flyers Are They Provided With The Drug Or To Persons Who Buy The Drug? Are They Necessary To Use The Drug? Do They Undermine Or Conflict With The FDA Approved Label? What If The Pharmacy Provides Them Independently of the Manufacturer?

12. 12 FDA Standards 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

13. 13 Federal Trade Commission Standards 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

14. 14 Tort Law Standards 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

15. 15 FDA Standard for an Rx Drug Label Labeling must include the established name, proprietary name (if any), adequate directions for use, and adequate warnings. The agency considers the approved product labeling, sometimes called the full prescribing information, to be adequate directions for use and adequate warning.

16. 16 Are there exceptions to the requirements for labeling? Reminder labeling, as defined in 21 CFR 201.100(f), is exempted. Reminder labeling calls attention to the name of the drug product but does not include indications or dosage recommendations for use. Reminder labeling may contain only the proprietary name of the drug, the established name of each active ingredient, and optionally, information relating to quantitative ingredient statements, dosage form, quantity of package contents, price, and other limited information.

17. 17 What the Label Cannot Have 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

18. 18 Patient Package Inserts 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?

19. 19 Promotional Materials 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?

20. 20 FDA Definition of Prescription Drug Advertising 21 CFR 202.1(l)1 states that advertisements subject to Section 502(n) of the Food, Drug, and Cosmetic Act (FD&C Act) include advertisements published in journals, magazines, other periodicals, and newspapers; and broadcast through media such as radio, television, and telephone communications systems. This is not a comprehensive list of advertising media subject to regulation. For example, FDA also regulates advertising conducted by sales representatives, on computer programs, through fax machines, or on electronic bulletin boards.

21. 21 What must a prescription drug advertisement include? Under section 502(n) of the FD&C Act, advertisements must include: the established name, the brand name (if any), the formula showing quantitatively each ingredient, and information in brief summary which discusses side effects, contraindications, and effectiveness. The brief summary is further discussed in 21 CFR 202.1(e)(1).

22. 22 Are there exceptions to the advertising regulations? Yes, there are a few exceptions but only to the requirement to provide a true statement of information in brief summary as required under 21 CFR 202.1(e)(1).

23. 23 21 CFR 202.1(e)(2) describes which ads are exempt: Reminder advertisements advertisements which call attention to the name of the drug product but do not include indications or dosage recommendations for use of the product, or any other representation. Reminder ads contain the proprietary name of the drug and the established name of each active ingredient. They may also contain additional limited information, such as the name of the company, price, or dosage form. Advertisements of Bulk-sale drugs Advertisements of prescription-compounding drugs promote sale of a drug for use as a prescription chemical or other compound for use by registered pharmacists.

24. 24 Providing Information On Unapproved Uses 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?

25. 25 Requirements for Direct to Consumer Ads 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

26. 26 Internet Information 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?

27. 27 Tort Implications of Direct Advertising 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?

28. 28 Future Issue 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