Regulatory Class - Nov 7

Question 1

What groups oversee advertising of prescription drugs, biologics and devices?

Answer 1

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

Question 2

Label vs Labeling

Answer 2

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)

Question 3

Requirements for Non-promotional drug labeling

Answer 3

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

Question 4

Package Insert: Highlights Section

Answer 4

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

Question 5

Package Insert: Full Prescribing Info

Answer 5

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

Question 6

Patient Labeling

Answer 6

Derived from professional labeling
Written in consumer friendly language
Focus on directions for use and risks associated with drug
The medication guide

Question 7

Medication Guide

Answer 7

For certain drugs with serious and significant risks

Distributed to patients each time the drug is dispensed

Question 8

Device Labeling Contents

Answer 8

 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)

Question 9

Fair Balance

Answer 9

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

Question 10

General package label requirements

Answer 10

 Manufacturer, packager or distributor’s name and
address
 Statement of ingredients  Expiration date
 Bar codes
 Statement of identity
 Quantity of contents
 Statement of dosage

Question 11

Professional labeling

Answer 11

For product use by healthcare professionals

Package insert - full prescribing info

Question 12

Specific populations addressed in full prescribing info

Answer 12

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

Question 13

For devices without clinical trials (510k), what are the side effects?

Answer 13

Side effects and warnings are listed as those typical of that type of device and/or procedures related to device use

Question 14

Distributing materials for off-label use

Answer 14

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

Question 15

Comparative or Superiority Claims

Answer 15

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

Question 16

Pharmacoeconomic (PE) claims

Answer 16

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

Question 17

FDA monitoring promo activity

Answer 17

Don’t care who in the company says it, only cares what is said
Monitors all promo exhibits at medical conferences and meetings

Question 18

Preapproval promo (drugs)

Answer 18

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

Question 19

Preapproval promo (devices)

Answer 19

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

Question 20

General advertising regulations

Answer 20

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)

Question 21

Reminder Ads

Answer 21

 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

Question 22

Help-seeking Ad

Answer 22

 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

Question 23

Using Spokespersons

Answer 23

 Company must disclose affiliation
 Physicians hired to speak on behalf of the company subject to regulations
 Information must be presented in compliant manner

Question 24

Direct to Print Consumer Ads

Answer 24

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

Question 25

Direct-to-Consumer Broadcast Ads

Answer 25

 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)

Question 26

Submission of drug promo material

Answer 26

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

Question 27

Submission of drug promo material - accelerated review

Answer 27

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

Question 28

Submission of device promo materials

Answer 28

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

Question 29

Press Releases

Answer 29

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

Question 30

Scientific Exchange

Answer 30

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.

Question 31

Regulations of type of article for reprints for unapproved uses

Answer 31

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

Question 32

Other requirements for disseminating articles for unapproved uses

Answer 32

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

Question 33

FDA’s “Bad Ad” Program

Answer 33

Educate healthcare practitioners regarding their role in reporting false or misleading promotional activities  Help FDA prevent misleading promotion of prescription drugs

Question 34

Administrative Actions

Answer 34

Notice of Violation (NOV) letters Warning Letters Recalls Delay, suspension or withdrawal of product approval *ultimately, the FDA declares the product misbranded

Question 35

Notice of Violation (NOV) letters

Answer 35

Also called, untitled letter  Minor health or safety issues  Require manufacturer to immediately stop using the violating materials Not all are publicly available

Question 36

Warning Letters

Answer 36

 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

Question 37

Corrective Actions

Answer 37

 Dear Health Care Professional Letters  Corrective Advertising  Recalls  Delay, suspension or withdrawal of product approval

Question 38

Dear Health Care Professional Letters (DHCPs)

Answer 38

 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

Question 39

Corrective Advertising

Answer 39

 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

Question 40

Judicial Actions

Answer 40

Injunction Seizure Criminal prosecution

Question 41

Injunction

Answer 41

FDA enjoins company from disseminating promotional materials – and possibly the product also Also, prevent them from selling the product

Question 42

Corporate Integrity Agreements (CIA)

Answer 42

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

Question 43

Ads exempt from Brief Summary

Answer 43

Help-seeking Ads Ads for bulk-sale Reminder Ads Ads for prescription compounding drugs

Question 44

Quality of Life Claims

Answer 44

claims drug as favorable, relative to patients daily life | Difficult to obtain as endpoint is too broad

Question 45

Ways FDA is made aware of non-compliant oral statements

Answer 45

Healthcare professionals inform FDA Competitors inform FDA FDA sends employees to events to monitor

Question 46

Primary difference between broadcast and print regulations

Answer 46

Print: brief summary accompanies Ad Broadcast: clear info about where consumer can get prescribing info

Question 47

Don'ts for Prescription drug advertising

Answer 47

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