1. Regulation of
Labeling and
Promotion
By
DR.Alaa Essmat

2. Legal Risks
• Drug Cannot Be Marketed
• Drug Can Be Removed From The
Market
• Civil Fines
• Criminal Prosecution
• Tort Judgments
• Bankruptcy
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3. 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!
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4. 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
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5. 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)
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6. 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."
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7. 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
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8. 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
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9. 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?
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10. 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?
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11. 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
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12. 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
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13. 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
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14. 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.
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15. 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.
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16. 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
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17. 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?
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18. 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?
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19. 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.
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20. 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).
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21. 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).
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22. 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. 22

23. 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?
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24. 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
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25. 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?
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26. 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?
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27. 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
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