This presentation was delivered to RAPS Convergence to update attendees about the state of the intended use rule and its impact on liability for communications in advertising and promotional labeling of prescription products.

1. Intended Use Rule
Update

2. What is the Intended Use Rule?
Intended use is defined in parallel for drugs and
devices
• 21 CFR § 201.128 (drugs)
• 21 CFR § 801.4 (devices)

3. Importance of Intended Use
Two primary ways for determining regulatory
category:
• Fiat (US Pharmacopoeia, National Formulary,
or Homeophathic Pharmacopoeia)
—21 USC § 321(g)(1)(A)
• Intended use
“articles intended for use in the diagnosis,
cure, mitigation, treatment, or prevention of
disease in man or other animals”
—21 USC § 321(g)(1)(B)

4. Impact of Intended Use Determination
Category determination affects:
• Premarket approval requirement
• Manufacturing requirements
• Approval pathway
• Labeling
• Commercialization
• Promotion
• Post-marketing reporting requirements

5. 21 CFR § 201.128
“The words intended uses or words of similar import ... refer to the objective intent of
the persons legally responsible for the labeling of drugs. The intent is determined by
such persons' expressions or may be shown by the circumstances surrounding the
distribution of the article. This objective intent may, for example, be shown by labeling
claims, advertising matter, or oral or written statements by such persons or their
representatives. It may be shown by the circumstances that the article is, with the
knowledge of such persons or their representatives, offered and used for a purpose
for which it is neither labeled nor advertised. The intended uses of an article may
change after it has been introduced into interstate commerce by its manufacturer. If,
for example, a packer, distributor, or seller intends an article for different uses than
those intended by the person from whom he received the drug, such packer,
distributor, or seller is required to supply adequate labeling in accordance with the
new intended uses. But if a manufacturer knows, or has knowledge of facts that would
give him notice, that a drug introduced into interstate commerce by him is to be used
for conditions, purposes, or uses other than the ones for which he offers it, he is
required to provide adequate labeling for such a drug which accords with such other
uses to which the article is to be put.”

6. Essential Elements of IU
4 key elements
• Standard for determining IU: Objective Intent
• Evidentiary basis: Expressions or
circumstances
• Variability: Can change after approval
• Knowledge Sentence

7. Knowledge Sentence
“[I]f a manufacturer knows, or has knowledge of
facts that would give him notice, that a drug
introduced into interstate commerce by him is
to be used for conditions, purposes, or uses
other than the ones for which he offers it, he is
required to provide adequate labeling for such a
drug which accords with such other uses to
which the article is to be put.”
—21 CFR § 201.128

8. Infamy of the Knowledge Sentence
• Different in kind from the other parts of the
definition
• Actions leading to knowledge sentence basis
for IU originate with others than manufacturer
• Mental state (knowledge of) rather than
behavior (such as labeling and promotion)
• Manufacturer might object to such uses

9. Why Change?
• Congress granted FDA regulatory authority over
tobacco products
• Law made use of “intended use” to define
tobacco products
• Law also excluded drugs, devices, and
combination products from FDA’s tobacco
authority
• FDA stated there was “ambiguity” about when a
product made or derived from tobacco was a
drug or device and when it was a tobacco product

10. FDA’s Initial 2015 Proposal
• Delete the knowledge sentence
• Tweak the rest of 21 CFR § 201.128 &
21 CFR § 801.4

11. FDA’s “Final” 2017 Proposal
Added a new sentence:
“And if the totality of the evidence establishes that a
manufacturer objectively intends that a drug introduced
into interstate commerce by him is to be used for
conditions, purposes, or uses other than ones for which it
is approved (if any), he is required, in accordance with
section 502(f) of the Federal Food, Drug, and Cosmetic
Act, or, as applicable, duly promulgated regulations
exempting the drug from the requirements of section
502(f)(1), to provide for such drug adequate labeling that
accords with such other intended uses”

12. Objections
• Created a new standard
“totality of the evidence”
• FDA asserted “may rely on any relevant source
of evidence of intended use”
• Promulgated as part of the “final rule”
• No comment period
• MIWG filed a petition to delay the rule
• New administration

13. FDA’s Response
• Initial 30-day delay (blanket administration
policy)
• Further one-year delay (citing MIWG)
• Indefinite delay in March of 2018
(promulgating the rest of the rule)

14. Where Things Stand
• We’re back to the pre-2015 definition of
intended use
• Agency claims to be “diligently” working to
clarify the definition

15. Key Takeaways
• Impossible to predict timeframe for action
• Need to pay attention to seemingly unrelated
rules
• FDA assertion of ability to “rely on any
relevant source of evidence” (emphasis in
original) to determine IU

16. QUESTIONS?
Contact info:
Dale Cooke
DCooke@PhillyCooke.com
@PhillyCooke

17. Dale Cooke
Dale Cooke is the president of PhillyCooke Consulting, which helps companies communicate about FDA-
regulated products using 21st century tools, while remaining compliant with regulations written in the
1960s. Dale has worked with more than 50 pharmaceutical and medical device clients and more than 20
advertising agencies around the world. His insights have been featured in the Wall Street Journal’s
Health blog, The Pink Sheet, Stat News, Law360, and other publications. Dale is an active member of
the Regulatory Affairs Professionals Society (RAPS), Drug Information Association (DIA), Food and Drug
Law Institute (FDLI), the Alliance for a Stronger FDA, and the Google Health Advisory Board.
Dale is the author of Effective Review and Approval of Digital Promotional Tactics, which is now in its
second edition in FDLI’s Topics in Food and Drug Law series. He is regularly invited to speak at industry
conferences on topics including FDA enforcement trends, best practices for review processes, global
review practices, and life sciences use of social media. Previously, Dale served as the head of Regulatory
for Digitas Health LifeBrands, which is part of the Publicis Healthcare Communications Group.
Dale earned his B.A. in Philosophy from Southern Methodist University, an M.A. in Philosophy from the
University of Arizona, and studied Epidemiology and Biostatistics at Drexel University’s School of Public
Health and Healthcare Compliance at Seton Hall University’s School of Law. Dale is currently enrolled at
Drexel University’s Kline School of Law with anticipated JD completion in 2019.