FDA, Labeling, and
Marketing
David W Feigal, Jr MD MPH
Adjunct Professor, O’Connor College of Law, ASU
January 16, 2016
Workshop: Pharmaceutical Pricing
and Marketing: Markets versus
Regulation
“When I use a word” Humpty Dumpty
said in a rather scornful tone, “it means
just what I chose it to mean – neither
more nor less.”
Lewis Carroll
What’s in a word (to FDA) ?
Label
Container and packaging labels
“Accompanying Materials”
Brochures, pamphlets, books…
Labeling
Exchange of Scientific Information
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Why is labeling important to FDA?
The Pure Food and Drug Act 1906
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Labeling (Speech) determines if an article is a Drug
In the FDCA, the term "drug“ means —
articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease, and
articles (other than food) intended to affect the structure
or any function of the body.
The same compound could be a drug or not – depending
on the intended use.
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Intent is determined by labeling (speech) ,i.e., the
packaging
The Courts and Labeling: False Claims
United States v. Johnson 1911
“This is an indictment for delivering for shipment from Missouri to
Washington, D.C., packages and bottles of medicine bearing labels that stated
or implied that the contents were effective in curing cancer, the defendant
well knowing that such representations were false. ”
“…a word as to what Congress was likely to attempt. It was much more
likely to regulate commerce in food and drugs with reference to plain matter
of fact, so that food and drugs should be what they professed to be …”
In other words, the Supreme Court interpreted that false and misleading
applied only to the contents of a drug packaging, not the health claims
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The Shirley Amendment 1912
Misbranding: IN CASE OF DRUGS:
“If its package or label shall bear or contain any statement, design, or
device regarding the curative or therapeutic effect of such article or any of
the ingredients or substances contained therein, which is false and
fraudulent.”
37 Stat. 416 (1912)
Note:
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Now a stricter standard than false and misleading for claims
Removed from the FDCA in 1938
Moot after 1979 when the drug approval process included strict labeling
requirements before marketing – labeling which cannot be changed without
FDA approval
Label and Labeling Court Decisions
1906 - 1938
1911 – Supreme Court: false and misleading does not apply to
medical claims
1912 – Shirley Amendment – Fraudulent medical claims prohibited
1916 -Supreme Court agrees that labeling definition includes
“accompanying materials”
Court cases for the next three decades define “accompanying” and the
boundaries of “interstate commerce”
1922 – Supreme Court: false claims constitute unfair competition
False drug claims become the majority of the FTC case load
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The “Elixer of Sulfanilamide”
FDA Takes Misbranding Action
The labeling described the product as an “Elixir of
Sulfanilamide”
For drug products an elixir contains alcohol
As there was no alcohol in the product FDA could seize
and destroy the product
Only the Misbranding (Speech) allowed FDA to take
action to seize and destroy the product
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What’s in a word (to FDA) ?
Label
Labeling
Prescribing Information (Package Insert)
Instructions for Use (Medical Devices)
Medication Guide (Safety information for patients)
Consumer Labeling (e.g., Food label, OTC label)
Promotion
Advertising
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Exchange of Scientific Information
1938 Food Drug & Cosmetic Act
Established basic structure of today’s law
Gave FDA authority to require New Drug Applications
FDA could block new drugs if it concluded that additional
safety testing needed
Prohibition of false therapeutic claims (not just fraud)
FDA now needed to define “New Drugs”
Misbranding is the authority that FDA uses to control
unapproved drugs
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Definitions: “New” Drug
The term "new drug“ means:
Any drug, the composition of which is
not generally recognized, among experts qualified by
scientific training and experience to evaluate the safety
and effectiveness of drugs, as safe and effective for use
under the conditions prescribed, recommended, or
suggested in the labeling thereof.
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Adequate Directions for Use
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OTC v RX “Adequate Directions for Use”
“Adequate Directions for Use” only applies to products
sold directly to consumers
An OTC product that cannot provide adequate
directions for use is a prescription product (Rx)
Until 1945 Rx drugs could not mention intended uses
An prescription (Rx) product is exempt from “adequate
directions for use” if it follows the prescription labeling
and promotion regulations
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Label and Labeling
1938 - 1962
1948 – Supreme Court: Labeling is defined “functionally”
1956 – Court of Appeals: Sales force materials are labeling
1960 – Congressional Hearings on biased materials supplied to
physicians by manufacturers
1960 – FDA asks medical textbook author to warn of unsafe
(off-label) uses
1962 – Kefauver Amendments return Rx advertising to FDA
(from FTC)
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Off label use v. Off label promotion
Off label use
Use in the practice of medicine of a product for indication not
included in FDA prescribing labeling
Not prohibited
Often standard of care
Often reimbursed
Off label promotion
Proactive communications about an indication not included in
FDA prescribing information
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What is “Off-Label” promotion?
Not a term found in the
Food Drug and Cosmetic Act, nor the
Regulations, and
not very often in FDA Guidance documents
The FDA Term is “Misbranded”
(but not every type of misbranding is off-label…)
FDA uses violations of the “New Drug” requirements to
prohibit off-label use
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Label and Labeling
1962 to 1997
1968 – Congressional hearings on off-label use of methotrexate for psoriasis
1971 – FDA ‘educational approach’ through journal articles …Congress not
impressed
1972 – FDA proposed rule to take action when physician off-label use created
public health threat
Vigorous push back from medical groups
FDA shifts emphasis to manufacturers
1984 Direct to Consumer advertising of Rx drugs begins
1991 FDA prohibit distribution of text books by manufacturers if they contain
off-label uses
FDA takes actions against manufacturers for distribution of medical literature
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What is in a word (to FDA) ?
Label
Labeling
Exchange of Scientific Information
Response to requests for information about an labeled or
unlabeled indication
Most companies differentiate between their sales force (detailers) and
have a separate group to respond to requests (often called Medical or
Scientific Affairs
Distribution of journal articles, professional society recommendations,
white papers, company safety experience
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FDA Review of Labeling
Organization of Prescription Drug Labeling Reviews
New Drug Divisions
Prescribing Information, Medguides, some patient materials
- Approves labeling changes
Division of Drug Marketing, Advertising and Communication
(old Name)
Office of Prescription Drug Promotion
Advertisements, sales force materials, web-sites
- Issues ‘notice of violation’ and ‘warning’ letters
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Off Label Promotion vs. Scientific
Exchange
Proactive Marketing v. Reactive Information Requests
1995 FDA refers off-label promotion cases to DOJ
1996 and 1997 FDA guidances to create safe harbors
Enjoined after WLF suit
1997 FDAMA
Compromise that no one liked
Off label use could be proactively marketed if a company was pursing an Efficacy
Supplement to their NDA to add that application
WLF decision / Appeal decision based on “safe harbor”
Law sunsets 2006
Subsequent 2009 Guidance by FDA on Scientific Exchange
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Labeling and Social Media
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Is Off Label Promotion Illegal?
“Promoting an approved drug for off-label uses is not itself a
prohibited act under the FDCA, nor is it an element of any
prohibited act.” Brief of United States, United States v.
Caronia, Nos. 09-5006, 10-0750, 2010 WL 6351497, at *51 (2d
Cir., filed Oct. 8, 2010).†
However
Is it evidence of intent to defraud, infringe patents,
misbrand a product?
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† as discussed in http://druganddevicelaw.blogspot.com/ January 15, 2016
Off-Label Promotion: Why does it
Matter?
Enforcement actions by FDA for misbranding
Whistle-blower suits for defrauding the government
health care purchasers
Violations of anti-kick back laws
Exposure to ‘failure to warn’ product liability actions
(Wyeth v. Levine)
Pre-empted for generic drugs which do not control their own
labeling (Pliva v. Mensing)
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Off-Label and the 1st Amendment
Commercial Free Speech
? Is off-label promotion entitled to 1st amendment
protection
? Does the government have an interest in restricting
dissemination of truthful information
? Who vettes “truthful”
? Are there alternatives to categorical prohibition
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FDA’s Dilemmas
Categorical prohibition of Off-Label information
While only applying to manufacturers – manufacturers often
possess more information about their use than any other source
FDA acknowledges the public health importance of off-label use
How is the public health served by off-label use without
off-label information? Is the patient held hostage to
FDA’s goal of encouraging NDA applications?
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