Regulatory Class - Nov 7 Flashcards
What groups oversee advertising of prescription drugs, biologics and devices?
CDER - Office of Prescription Drug Promotion [OPDP] (formerly DDMAC)
CBER - Advertising and Promotional Labeling Branch
CDRH - Office of Compliance
Act specifically gives right for enforcement of drugs but it also applies to biologics and devices
Label vs Labeling
Label - written, printed, or graphic material on the drug’s immediate container (physical packing item)
Labeling - any written, printed or graphic material on the drug product; containers or wrappers; any materials issued in association with the drug (including drug promotion)
Requirements for Non-promotional drug labeling
Contain summary of essential scientific info
Be submitted to FDA with marketing application
Be updated when new safety info becomes available (require supplement)
Cannot contain false or misleading statement
Cannot be promotional
Package Insert: Highlights Section
Package inserts are made for pharmacists
Statement that not info is included in the highlights
Drug names, dosage form, route of administration
Date of initial FDA approval
Boxed warning
List of recent (w/in 1 yr) changes to labeling
Indications for use
Contraindications, warnings and precautions, adverse reactions, and drug interactions
Use in specific populations
Patient counseling info
Date of most recent revision
Package Insert: Full Prescribing Info
Contents Boxed Warning Indications and usage Dosage and administration Dosage forms and strengths Contraindications (known hazards) Warnings and precautions (AEs with frequency) Adverse reactions (only those associated with drug) Drug interactions Use in specific populations (pregnancy, pediatrics, geriatrics) Drug abuse and dependence Overdose Drug description Clinical pharmacology (Mechanism of action, PK) Nonclinical toxicology Clinical Studies How supplied, and storage and handling Patient counseling info
Patient Labeling
Derived from professional labeling
Written in consumer friendly language
Focus on directions for use and risks associated with drug
The medication guide
Medication Guide
For certain drugs with serious and significant risks
Distributed to patients each time the drug is dispensed
Device Labeling Contents
Manufacturer name and principal place of business (so, they can be contacted) Device name and Established name Description Indications and usage Contraindications Warnings Precautions Use in specific patient populations Adverse reactions Prescription device statement Date of issue/revision of labeling Need to include operations, servicing, and calibration info and any info necessary for the user (usually given as a user's manual)
Fair Balance
All claims of effectiveness must be accompanied by info about product’s risks
Marked by the amount of info and its format (where it’s located in the Ad)
Applies to each piece of promo material
Must be an adequate representation of all risks
Must refer readers to risk info in multipage Ad
Most frequently violated
General package label requirements
Manufacturer, packager or distributor’s name and
address
Statement of ingredients Expiration date
Bar codes
Statement of identity
Quantity of contents
Statement of dosage
Professional labeling
For product use by healthcare professionals
Package insert - full prescribing info
Specific populations addressed in full prescribing info
These populations must be address in the prescribing info, even if only to say, not applicable. Pregnancy Labor and delivery Nursing mothers Pediatric use Geriatric use
For devices without clinical trials (510k), what are the side effects?
Side effects and warnings are listed as those typical of that type of device and/or procedures related to device use
Distributing materials for off-label use
A lot of constraints, so not used too much
Must be a plan in place for a trial for this use
Cannot use a competitor’s materials
Must submit to FDA 60 days prior to dissemination
Must maintain records of persons receiving the info
Constraints:
Drug is approved for another use
Information is directed to healthcare practitioner
Reprint/copy of article in peer-reviewed scientific or medical journal discussing scientifically sound clinical trial
Does not pose significant risk to public health
Not false or misleading
Not derived from clinical trial conducted by another manufacturer
Disclose that use is not approved/cleared
Comparative or Superiority Claims
Cannot make claims that a product is better, safer, more effective, unless demonstrated by substantial evidence
Substantial evidence must include:
Usually requires 2 adequate and well-controlled trials
Head-to-head clinical trials
Comparison must be clinically and statistically significant
Pharmacoeconomic (PE) claims
Cost-effectiveness claims, do not include clinical efficacy
Must be based on competent and reliable evidence, directly related to an approved indication
Data not based on studies but scientific cost-modeling
May only be provided to formularies, insurance companies, manage-care providers
FDA monitoring promo activity
Don’t care who in the company says it, only cares what is said
Monitors all promo exhibits at medical conferences and meetings
Preapproval promo (drugs)
Cannot represent that an investigational drug (or use) is safe and effective
Exceptions:
Institutional Ads - company states it’s doing research in an area but can’t mention drug name: goal is to get physicians to call about the study and then any convo about the drug is not promotional
Coming Soon promo - can only reveal the name, no suggestions of use for indications or claims of safety or efficacy, cannot be used for drugs with black box warnings
Must choose only 1 of the 2 exceptions, not both
Preapproval promo (devices)
Can advertise when device is pending approval or clearance but must disclose current regulatory status
Cannot:
Take orders
Make claims regarding safety or effectiveness
Make comparative claims
General advertising regulations
Must contain a brief summary of side effects, warnings, precautions and contraindications (taken from product label and usually printed on adjacent page)
Must include reference to generic drug name (most everytime the brand name is mentioned; directly right or beneath brand name; font size at least half as large)
Reminder Ads
Call attention to the name of the drug
Do not make claims or include indications or dosage recommendations for use
Not allowed for products with Boxed Warning in the label
Include brand name and generic name
Help-seeking Ad
Inform consumers about a specific medical condition
and
Encourage them to talk to their healthcare provider about the condition
Do not mention any product name
May identify company and provide telephone number or website
Identifies the condition, not the drug
Using Spokespersons
Company must disclose affiliation
Physicians hired to speak on behalf of the company subject to regulations
Information must be presented in compliant manner
Direct to Print Consumer Ads
Must include statement: You are encouraged to report negative side effects of prescription drugs to the FDA.
Written in language understood by consumers
Include statement that risk information is not comprehensive
Provide toll-free telephone number and/or website for more information
Direct-to-Consumer Broadcast Ads
Must not be false or misleading
Present fair balance
Provide all information relevant to product’s indication
Include a “major statement” of primary risks in audio/video presentation
Make brief summary or provide for dissemination of approved package labeling (doesn’t relieve duty of fair balance)
Submission of drug promo material
All promotional materials must be submitted to OPDP at the time of initial publication or dissemination (first use)
Use Form FDA 2253
Under standard review, not required to submit promotional materials for prior review and comment
Although industry practice to submit
Direct-to-consumer TV ads generally submitted to OPDP for preclearance prior to dissemination
Not required but industry practice
FDA may require preclearance if the company has
committed serious or repeated violations
Submission of drug promo material - accelerated review
Accelerated approval – must submit draft promotional materials for FDA comment ≥ 30 days prior to dissemination
Until FDA removes this requirement
During initial NDA review under accelerated approval, all promotional materials intended to be used in the first 120 days following approval must be submitted to OPDP for review
Submission of device promo materials
CDRH does not require submission of advertising and promotional materials
Draft labeling is included in marketing submissions
Can submit promo material for preclearance, but it’s considered advice, not binding
Press Releases
FDA regulated, and must show:
Fair balance
No false or misleading content No preapproval promotion
FDA does not take action against companies when their communications are exclusively to financial community
“Good idea” to submit major announcements to the FDA prior to release
Scientific Exchange
Occurs at CE events (must be non-promotional)
Scientific activity must be independent of manufacturer influence
Can respond to unsolicited requests for info from healthcare professionals
This (off-label) solicited info must come from scientific department in the company and not the sales reps.
Regulations of type of article for reprints for unapproved uses
Scientific or medical journal:
Published by organization with an independent, expert editorial board and a policy of full disclosure of conflict of interest
Peer-reviewed
Not funded by manufacturer
Not primarily distributed by manufacturer
Not written, edited or published at the request of or significantly influenced by manufacturer
Scientific or medical journal article addresses adequate and well-controlled study:
Scientifically sound
Not false or misleading
Does not pose significant risk to public health
Does not include: letters to editor, abstracts, Phase I studies in healthy subjects
Other requirements for disseminating articles for unapproved uses
Manufacturer must provide:
Unabridged reprint
Not marked, highlighted or characterized by manufacturer
Approved labeling
Bibliography of publications regarding the off-label use
Representative publication with different conclusions regarding the off-label use
Include:
Statement that off-label use not approved/cleared by FDA Disclose if authors have financial interest
Identify any significant risks not included in journal article
Promotional materials must be distributed separately
FDA’s “Bad Ad” Program
Educate healthcare practitioners regarding their role in reporting false or misleading promotional activities
Help FDA prevent misleading promotion of prescription drugs
Administrative Actions
Notice of Violation (NOV) letters
Warning Letters
Recalls
Delay, suspension or withdrawal of product approval
*ultimately, the FDA declares the product misbranded
Notice of Violation (NOV) letters
Also called, untitled letter
Minor health or safety issues
Require manufacturer to immediately stop using the violating materials
Not all are publicly available
Warning Letters
Serious health issues or repeated minor issues
Require response within 15 days and corrective action in addition to stopping violating action
Publicly available
Sponsor has 15 days to respond to the letter
Corrective Actions
Dear Health Care Professional Letters
Corrective Advertising
Recalls
Delay, suspension or withdrawal of product approval
Dear Health Care Professional Letters (DHCPs)
Sent to HCPs who use the company’s products
Typically appear in same venue as violating materials
E.g. journal advertisement – letter would be in same journal for same time period that ad ran
Corrective Advertising
Reviewed and approved by FDA
Identified as corrective ad and required by FDA
Explain how it addresses violations
Run in same publication as violating ad
Judicial Actions
Injunction
Seizure
Criminal prosecution
Injunction
FDA enjoins company from disseminating promotional
materials – and possibly the product also
Also, prevent them from selling the product
Corporate Integrity Agreements (CIA)
between Companies and the Office of Inspector General (OIG)
Made with companies with serious violations and charges of false claims
Companies claim responsibility for all promotional materials and investigational materials
Companies must payback medicare/medicaid for payment of the fraudulent drug promotion
Requires 5 years of compliance and follow-up with additional oversight, training, and reporting to OIG
Ads exempt from Brief Summary
Help-seeking Ads
Ads for bulk-sale
Reminder Ads
Ads for prescription compounding drugs
Quality of Life Claims
claims drug as favorable, relative to patients daily life
Difficult to obtain as endpoint is too broad
Ways FDA is made aware of non-compliant oral statements
Healthcare professionals inform FDA
Competitors inform FDA
FDA sends employees to events to monitor
Primary difference between broadcast and print regulations
Print: brief summary accompanies Ad
Broadcast: clear info about where consumer can get prescribing info
Don’ts for Prescription drug advertising
Ingredient info must be complete and uninterrupted
No fanciful proprietary name
Don’t feature inactive ingredients as beneficial
Display at least one specific dosage form
Can use a single term for a group of side effects
Cannot use favorable nonclinical lab data to suggest clinical significance
Cannot use statistical significance to demonstrate clinical significance
