Highlights of Recent FDA Guidances
0, 2015 | 90 minutes | 2:00 – 3:00 p.m. EST
Speakers:
Julie Chronis, Regulatory Counsel, Office of Prescription Drug Promotion, Center for Drug Evaluation and Research, Office of Medical Products and Tobacco, FDA
Roberta Szydlo, Senior Regulatory Review Officer, Office of Prescription Drug
Promotion, Center for Drug Evaluation and Research, Office of Medical Products and Tobacco, FDA
Moderated by Michael Sauers, Staff Supervisor, Office of Prescription Drug
Promotion, Center for Drug Evaluation and Research, Office of Medical Products and Tobacco, FDA
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Revised Draft Guidance for Industry:
Brief Summary and Adequate Directions for
Use: Disclosing Risk Information in
Consumer-Directed Print Advertisements and Promotional Labeling for
Prescription Drugs – Revision 2
Julie Chronis, J.D.
Senior Regulatory Counsel
Office of Prescription Drug Promotion
FDLI – Advertising and Promotion
Oct. 2, 2015

• The revised draft guidance:
– applies to prescription drug product (and biological product) DTC advertisements in print media
– Refers to the requirement that an advertisement for a drug disclose each side effect, warning, precaution, and contraindication from the labeling as the brief summary requirement (See 21 U.S.C. 352(n); 21 CFR
202.1(e)(1), (e)(3)(iii))
Does not refer to the presentation of risk information in the main body of the ad

• 2004 draft guidance: Brief Summary:
Disclosing Risk Information in Consumer-
Directed Print Advertisements
(CDER, CBER)
– 2004 draft guidance recommended
1. FDA-approved patient labeling
2. Highlights
3. Consumer-friendly language
– Asked for specific information to be addressed in comments to be submitted to docket

• 37 comments received to the 2004 docket
• Social Science research
– Aikin, KJ, AC O’Donoghue, J Swasy, and HW
Sullivan, 2011, A Randomized Trial of Risk
Information Formats in Direct-to-Consumer
Prescription Drug Advertisements, Medical Decision
Making, 31:23-33
– http://www.fda.gov/AboutFDA/CentersOffices/Officeof
MedicalProductsandTobacco/CDER/ucm090276.htm

• Feb. 2015 revised draft guidance – Brief
Summary and Adequate Directions for
Use: Disclosing Risk Information in
Consumer-Directed Print Advertisements and Promotional Labeling for Human
Prescription Drugs – Revision 1
CDER/CBER
• Received comments to the docket

• Aug. 2015 - Revision 2 - [same title]
CDER/CBER /CVM
• Revision 2 was issued to incorporate animal prescription drugs; there are no other revisions
• Docket closes Oct. 5, 2015
– It is not necessary to resubmit comments

Importance of This Revised Draft Guidance
• Incorporates animal prescription drugs
– There are no other differences between Revision 1 and 2
• Responds to stakeholder requests for clarification
– Clarifies risk information that should be included
– Recommends formatting options

Importance of This Revised Draft Guidance
• Contains new recommendations for consumer-directed print promotional labeling
– Recommends the full PI not be included
– Instead, use the same content and format as the “consumer brief summary”
• Advances FDA’s mission in protecting public health

Which format or formats present risk information in the most useful manner?
• Traditional
• Question & Answer
• Highlights
• Prescription Drug Facts Box

Traditional

Highlights

Q&A

Prescription Drug
Facts Box

• Mall-intercept with 300 participants
• Ever been told by HCP you were overweight & needed to lose > 15 pounds?

• Computer-administered
• Viewed 1 of 4 formats
• Viewed all 4 formats
Questions
Questions

12 “True or False” questions
“You must be at least 18 years old to take Oncazil”

9 Questions
“ How confident are you that you could identify which drugs interact with Oncazil?”
0 ( no confidence ) -- 10 ( complete confidence )

10 Questions
“The way the information was presented on this page was useful”
1 ( strongly disagree ) to 5 ( strongly agree )

6 questions
“How easy it is to read this page”
1----2----3----4----5----6----7----8----9----10
Not at all easy
Extremely easy

Please rank the versions by clicking on the ad you prefer most

Of the remaining ads, click on the ad you prefer most

Drug Facts Box > Traditional

Drug Facts Box > Traditional

Drug Facts Box > Highlights, Traditional
Q & A > Traditional

Drug Facts Box > All others
Q & A > Highlights, Traditional

1
3 2 4
Drug Facts Box
Q & A Traditional Highlights

Drug Facts Box
Q & A Traditional Highlights

Aikin KJ, O’Donoghue AC, Swasy J, Sullivan HW.
A randomized trial of risk information formats in direct-to-consumer prescription drug advertisements.
Medical Decision Making, 2011;31:E23-E33.

“Consumer Brief Summary”
Consumer-directed print advertisements or promotional labeling for prescription drug products
1. Advertisements – brief summary requirement
2. Promotional Labeling – adequate directions for use requirement (the requirement that certain information set forth in 21 CFR 201.100(d) or 201.105(d) be included
(generally fulfilled by including the PI) (see p. 2-4)
For purposes of the revised draft guidance, the consumerdirected document recommended as an alternative to the full PI or the risk portions of the PI is referred to as the “ consumer brief summary .”

Recommendations regarding the
“Consumer Brief Summary”
• Language
– Consumer-friendly language
• Avoid medical jargon
• Engage the reader
• Readability
– Use known elements to improve
• White space
• Branded colors

Recommendations regarding the
“Consumer Brief Summary”
• Content
-
– Clinically significant information on the most serious and most common risks associated with the product
• Not necessarily every single risk
– Look to Highlights
• But include additional details

Recommendations regarding the
“Consumer Brief Summary”
• Content cont. -
– Boxed Warning
– All Contraindications
– Certain information regarding Warnings and
Precautions
• Most clinically significant information
• Information that would affect a decision to prescribe or take a drug
• Lab tests
• Special precautions (not in other portions)
• Measures that can prevent or mitigate harm

Recommendations regarding the
“Consumer Brief Summary”
• Content cont.
-
– Most frequently occurring Adverse Reactions
– Other material information regarding risks
– Statement regarding how to obtain more information
– Indication, Interactions, Special Populations
– Don’t need certain information, e.g., dosage and administration

Recommendations regarding the
“Consumer Brief Summary”
• Format # 1 – Prescription Drug Facts Box
– Similar to OTC Drug Facts Box
• Standardized headings, e.g. Uses, Warning, Ask a health care provider before use if . . .
• Format #2 – Question and Answer
– Present information in Q&A format - e.g.
• What is [drug X] used for?
• When should I not take [drug X]?
• What should I tell my health care provider?

Summary
• Revision 2 draft was issued to include animal prescription drugs.
• FDA recommends firms include the same information in consumer-directed print advertising and promotional labeling pieces, i.e., the “consumer brief summary.”
• Specific recommendations regarding the content and format of the consumer brief summary are set forth in the revised draft guidance.
• FDA does not intend to object for a failure to include certain other information or the entire PI to fulfill the brief summary and adequate directions for use requirements if firms follow the revised draft guidance.

Specific Comments Requested
• Is the recommended content and format the most useful information for consumers in determining whether to take a medication or seek more information about a product, and if not, what information would be more useful?
• What relevant research has been conducted and what alternative formats were developed after we received comments on the 2004 draft guidance?
• In the revised draft guidance, FDA suggests that the adequate directions for use requirement be fulfilled by providing the consumer brief summary rather than the full PI for the product. FDA seeks comments regarding this recommendation.

Open Comment Period
• Comments due Oct. 5, 2015
– Online at www.regulations.gov
– In writing to the Division of Dockets Management
• Docket #FDA-2004-D-0500
– https://www.federalregister.gov/articles/2015/08/06/2015-
19244/brief-summary-and-adequate-directions-for-use-disclosingrisk-information-in-consumer-directed-print ( Federal Register
Notice )
– Brief Summary and Adequate Directions for Use: Disclosing Risk
Information in Consumer-Directed Print Advertisements and
Promotional Labeling for Prescription Drugs, Guidance for
Industry (PDF - 126KB) ( guidance link )

The Food and Drug Law Institute’s
Advertising and Promotion Conference
October 1-2, 2015
Washington, DC
Providing Regulatory Submissions in Electronic and NonElectronic Format ‒ Promotional
Labeling and Advertising Materials for Human
Prescription Drugs
CDR Roberta Szydlo, RPh, MBA, RAC, CGP
Office of Prescription Drug Promotion
FDA

• Background
• Why is the draft guidance important?
• When – Timeline for submissions in eCTD
• How to submit in eCTD
• What have we learned so far?
• Who – Contact information
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• Draft Guidance, Providing Regulatory
Submissions in Electronic and Non-Electronic
Format —Promotional Labeling and Advertising
Materials for Human Prescription Drugs, issued
April 21, 2015
• Explains how manufacturers, packers, and distributors (firms) that may either be the applicant or acting on behalf of the applicant, should make submissions pertaining to promotional materials for human prescription drugs and biologic products
(“drugs”) to the FDA
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• Pertains to submissions made to CDER (OPDP) and
CBER (APLB)
• Applies to human prescription drugs, including biological products that are defined as drugs. Does
NOT apply to devices that CBER regulates as biological products.
• Describes the various types of submissions of promotional materials and general considerations for submissions in paper or electronic format
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• Describes specific aspects of submission of promotional materials using module 1 (M1) of the electronic Common
Technical Document (eCTD) using version 3.3 or higher of the us-regional-backbone file
• The terms “promotional materials” and “promotional pieces” collectively refer to advertising (ads) and promotional labeling materials, regardless of the format, manner, or medium by which they are presented (For example television ads, detailing pieces, print ads, and radio ads)
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• For all types of submissions of promotional materials (both eCTD and non-eCTD):
– Formalized recommendations regarding what should be included with various types of submissions (e.g., subject lines, how many copies to include if paper, how to submit if in eCTD format)
– Provided formal definitions of various types of submissions (e.g., Withdrawal versus General
Correspondence)
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• Biggest change from
OPDP perspective: the draft guidance facilitates acceptance of eCTD submissions using the new M1 as of June 15, 2015
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– Faster and more efficient delivery to the reviewer
– Ability to accept non-2253 submissions in an electronic format (i.e., no paper submission necessary)
– Ability to receive eCTD 2253 and non-2253 submissions over same electronic submission gateway (ESG)
– Submission is available for all staff to see so secondary review and consultation of other offices is more efficient
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– Capability to automatically populate tracking database to improve processing efficiency
– Electronic search and filtering capabilities
– Opportunity for companies to develop streamlined processes to submit high volume
2253s electronically over the electronic submission gateway (ESG)
– Alignment with submission process for other submissions in CDER
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• Section 745A(a) of the Federal Food, Drug, and
Cosmetic Act (FD&C Act), added by section
1136 of the Food and Drug Administration
Safety and Innovation Act (FDASIA), requires that submissions under section 505(b), (i), or (j) of the FD&C Act, and submissions under section
351(a) or (k) of the Public Health Service Act
(PHS Act), be submitted in electronic format specified by FDA, beginning no earlier than 24 months after FDA issues a final guidance specifying such electronic submission format.
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Two types of promotional material-related submissions are considered subject to the requirements of section 745A(a):
• Promotional materials submitted in fulfillment of the postmarketing reporting requirements (i.e., Form FDA 2253 submissions or “2253 submissions”)
• Presubmission of promotional materials for accelerated approval products
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• Therefore, 24 months after the issuance of this guidance in final form, firms will be required to submit all promotional submissions that fall within section 745A(a) electronically (e.g., in eCTD format)
• Firms may ‒ and are strongly encouraged to ‒ submit electronically other types of promotional material submissions
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• All promotional submissions should:
– Include appropriate NDA, ANDA, or BLA number(s)
– Use the most specific material type (from Form FDA 2253)
– Submit different types of promotional material submissions separately (e.g., do not combine together a postmarketing 2253 and request for advisory submission)
– Submit promotional submissions separately from other types of submissions not related to promotion
– Submit promotional materials directed to HCPs separately from those directed to consumers
– Use Form FDA 2253 appropriately for OPDP vs. APLB
– NOT include Form 356h
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• Docket officially closed July 21, 2015
– Six submissions to the docket from stakeholders; currently under review.
• OPDP has been receiving a steady flow of
FDA Form 2253 submissions in eCTD since the week of June 15, 2015
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1. Be careful to use the correct version of M1.
– OPDP and APLB can both accept submission of promotional materials using version 3.3 or higher of the us-regional-backbone file
– APLB will continue to accept eCTD submissions using previous versions of
M1until 24 months after publication of the final version of this guidance
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2. Please do NOT include promotion-related correspondence in sections of eCTD used to provide correspondence for other parts of the agency (e.g., Section 1.2).
– Section 1.15.1 is dedicated to correspondence for promotional materials.
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3. Be careful to use the correct date format for eCTD submissions.
– The date format to be used is yyyymmdd
(four-digit year, two-digit month, and two-digit day)
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4. For 2253s, annotated versions of the promotional material(s), annotated labeling, and references are helpful to FDA, but optional.
– Only the clean version of the material in section 1.15.2.1.1 is required (along with current product labeling in Section 1.14.6).
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5. In cases where a company that holds the application collaborates with another firm in order to promote the drug, the application holder should send a general correspondence to OPDP/APLB describing the agreement.
• Subsequent submissions of promotional materials should also indicate the business relationship (e.g., Comments section on 2253 form, cover letter, etc.)
• For eCTD submissions, both companies should be using the same version of the us-regional-backbone file
• Both companies should work together to come up with a system for generating sequence numbers in order to avoid the use of duplicate sequence numbers (e.g., assign a block of numbers to a particular vendor)
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6. Please ensure that the most current FDA Form
2253 is submitted to ensure FDA database fields are automatically populated correctly and prevent processing delays.
– The most current FDA 2253 Form is available on the FDA Forms website .
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• Firms are encouraged to submit sample promotional submissions. To begin the process, email the Electronic Submission Support Team at ESUB@fda.hhs.gov
• CDER’s Office of Business Informatics’ eCTD
Webpage – contains Guidances, specifications, archives of eCTD presentations
• OPDP’s website substantially revised – check draft guidance first, then PMs are best resource for submission-related questions
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•
• Email address for questions regarding the draft guidance or eCTD submissions to OPDP:
OPDPeCTD@fda.hhs.gov
• Email address for general submission questions for OPDP: CDER-OPDP-RPM@fda.hhs.gov
• Email address for technical questions about eCTD: ESUB@fda.hhs.gov
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• Building 51 on White Oak Campus
– Suites 3200 & 3300
• Fax numbers
– (301) 847-8444 or (301) 847-8445
• Telephone number
– (301) 796-1200
• Submission address
Food and Drug Administration
Center for Drug Evaluation and Research
Office of Prescription Drug Promotion
ATTN: OPDP Project Manager
5901-B Ammendale Road
Beltsville, MD 20705-1266
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