1. RAC Study Group Chapter 16
Prescription Drug Labeling, Advertising and Promotion

2. 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

3. 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.

4. 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 )
Statement of ingredients (21 CFR ), including required warning statements for specific ingredients (e.g., FD&C Yellow No. 5 (21 CFR ))
Location of expiration date (21 CFR ) and significance of control numbers (21 CFR )
Bar code label requirements (21 CFR )
Statement of identity (21 CFR )
Declaration of net quantity of contents (21 CFR )
Statement of dosage (21 CFR )

5. 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

6. 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)
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

7. 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

8. Advertisement and Promotion Requirements
21 CFR “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

9. 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 (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

10. 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

11. 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 or call 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

12. 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