RAC Study Group Chapter 16
Prescription Drug Labeling,
Advertising and Promotion
Labels and Labeling
• “label” - defined in the act as a display of written,
printed or graphic material on the immediate
container of a drug
• “labeling” is a broader term encompassing any
written, printed or graphic material on the drug
product, any of its containers or wrappers or any
material issued in association with the drug
Labeling
• FDA-approved professional labeling (information for healthcare
professionals about approved uses of the drug), also referred to as the
prescribing information or the “package insert” (PI)
• FDA-approved patient labeling (drug information directed to patients) for
some drug products with serious risk(s) in the form of a Medication Guide
• Promotional labeling any material containing information intended to
promote the use of the drug. Even oral statements by sales representatives
are subject to regulation by FDA as “promotional labeling.” Unlike the PI
and patient labeling, promotional labeling is disseminated by a company
without a specific “approval” of the materials by FDA.
Title 21 of the Code of Federal Regulations
(CFR) Part 201
• Manufacturer, packager or distributor’s name and address (21 CFR 201.1)
• Location of National Drug Code (NDC) numbers (requested but not required) (21
CFR 201.2) (note: the determination of NDC numbers is included in 21 CFR
207.35)
• Statement of ingredients (21 CFR 201.10), including required warning statements
for specific ingredients (e.g., FD&C Yellow No. 5 (21 CFR 201.20))
• Location of expiration date (21 CFR 201.17) and significance of control numbers
(21 CFR 201.18)
• Bar code label requirements (21 CFR 201.25)
• Statement of identity (21 CFR 201.50)
• Declaration of net quantity of contents (21 CFR 201.51)
• Statement of dosage (21 CFR 201.55)
Additional 201
• Subpart C has the requirements for Over the Counter (OTC) products
• Subpart G has requirements for specific products like hormones,
sprays and powders
• FDAAA added safety update requirements
Physician Labeling
• Professional labeling, or package insert
• Compilation of product information based on FDA’s comprehensive review of
the sponsor’s approved NDA/BLA
• Adequate directions for use,” written to direct healthcare professionals’ use
of a drug product
• Amended in 2006 with the Physician Labeling Rule (PLR)
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Standard format with 3 main sections
Requires inclusion of contact information for adverse events reporting
Multiple FDA guidances to assist Sponsors
Specific font requirements and rules for amendments
Structured Product Labeling (SPL) is the electronic format for markups
Prescription Drug Promotion
• Office of Prescription Drug Promotion, or OPDP (formerly the Division
of Drug Marketing, Advertising and Communications, or DDMAC)
• Regulations covering prescription drug promotion are found in 21 CFR
202 and are cross-referenced to 21 CFR 201
• Administrative tools include Notice of Violation letters (NOV), or
“Untitled Letters;” issuing Warning Letters; ordering a recall; and
calling for the delay, suspension or withdrawal of a product approval,
or issuance of “Dear Doctor Letter”
• Judicial tools – barely used
• “Bad Ad” program
Advertisement and Promotion Requirements
• 21 CFR 312.7 “shall not represent in a promotional context that an
investigational new drug is safe or effective for the purposes for which
it is under investigation.”
• Must submit at time of dissemination, except subpart H – 30 days
prior to dissemination and those released within 120 days of
approval, must be submitted prior to approval
• Regulations require the most prominent mention of the brand name
to be accompanied by the generic name “in letters at least half as
large as the letters comprising the proprietary name or designation
with which it is joined
Advertisement and Promotion Requirements
• Risk information must have comparable prominence to the promotional
claims = Fair Balance
• No off label claims can be promoted
• Section 114 of the Food and Drug Administration Amendments Act of 1997
(FDAAA) provides for a legal mechanism to allow the promotion of
pharmacoeconomic claims – less stringent requirements
• Prescription drug advertising contain “True statement of information in
brief summary relating to side effects, contraindications, and effectiveness”
(21 CFR 202.1(e)). Promotional labeling that is not an advertisement (or
reminder labeling, as described below) must be disseminated with a copy
of the FPI
• Reminder advertising – not as stringent, not allowed for black box products
Advertisement and Promotion Requirements
• The PhRMA Code, which is a voluntary non-regulatory standard,
prohibits distribution of non-educational and practice-related
promotional materials, including such reminder items as pens,
notepads and mugs with product logos on them, even if the item is of
minimal value and related to the healthcare professional’s work or for
the benefit of the patient
• Help-seeking advertisement is intended to inform consumers about a
specific medical condition and encourage them to talk to their
healthcare professionals about the condition
• Neither bulk-sale drugs nor compounding drugs are permitted to
make safety or efficacy claims
Direct-To-Consumer (DTC) Advertising
• Television and radio must include a “major statement” of the product’s
primary risks
• A similar guidance is available for restricted medical devices
• Required – “You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit
www.fda.gov/Safety/MedWatch/default.htm, or call 1-800-FDA-1088”
• No social media guidance available, still discussing education versus
promotion
• FDA works with other agencies such as the US Attorney’s Office and OIG in
prosecuting companies alleged to be in violation of the FCA (False Claims
Act) or Anti-Kickback Statute through off-label promotion
In Summary
• All drug labeling, including container labels, package inserts, patient
labeling, Medication Guides and promotional labeling (including oral
statements), is subject to FDA regulation
• FDA monitors prescription drug advertising and promotion through the
OPDP. No drug can be promoted until the NDA has been approved by FDA
• All promotional materials must include a “fair balance” of efficacy and risk
information, with the exception of reminder labeling (not allowed for
products with a Boxed Warning). Broadcast advertisements must include a
“major statement” of risk
• All non-reminder promotional materials must be accompanied by the full
prescribing information; advertisements require an accompanying “brief
summary” of the FPI. Broadcast advertisements must include “adequate
provision” for the dissemination of the approved labeling