1. Patient Engagement in the FDA Process
Highlights of Recent FDA Guidances0, 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

2. FDLI – Advertising and Promotion
Revised Draft Guidance for Industry: Brief Summary and Adequate Directions for Use: Disclosing Risk Information in Consumer-Directed Print Advertisements and Promotional Labeling for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

3. “Brief Summary Requirement”
The revised draft guidance: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

4. History of Revised Draft Guidances
2004 draft guidance: Brief Summary: Disclosing Risk Information in Consumer-Directed Print Advertisements (CDER, CBER)
2004 draft guidance recommended
FDA-approved patient labeling
Highlights
Consumer-friendly language
Asked for specific information to be addressed in comments to be submitted to docket

5. History of Revised Draft Guidances
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

6. History of Revised Draft Guidances
Feb revised draft guidance – Brief Summary and Adequate Directions for Use: Disclosing Risk Information in Consumer-Directed Print Advertisements and Promotional Labeling for Human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

7. History of Revised Draft Guidances
Aug 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

8. 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

9. 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

10. Brief Summary Format Study
Which format or formats present risk information in the most useful manner?
Traditional
Question & Answer
Highlights
Prescription Drug Facts Box

11. Traditional

12. Highlights

13. Q&A

14. Prescription Drug Facts Box
This format is based on the OTC Drug Facts format, which is in turn based on much research conducted in the 1990s.

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

16. Method Computer-administered Viewed 1 of 4 formats Questions
Viewed all 4 formats Questions

18. Selected Measures . . .

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

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

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

22. Attitude toward the Ad 2
6 questions
“How easy it is to read this page”
Not at all Extremely
easy easy

23. Preference Please rank the versions
by clicking on the ad you prefer most

24. Preference
Of the remaining ads, click on the ad you prefer most

25. Significant Results

26. Drug Facts Box > Traditional
Risk Comprehension
Drug Facts Box > Traditional

27. Drug Facts Box > Traditional
Confidence
Drug Facts Box > Traditional

28. Drug Facts Box > Highlights, Traditional
Attitude toward the Ad
Drug Facts Box > Highlights, Traditional
Q & A > Traditional

29. Attitude toward the Ad 2 Drug Facts Box > All others
Q & A > Highlights, Traditional

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

31. Summary
Drug Facts Box
Q & A
Traditional
Highlights

32. Reference 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.

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

34. 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

35. 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

36. 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

37. 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

38. 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?

39. 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.

40. 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.

41. Open Comment Period Comments due Oct. 5, 2015 Docket #FDA-2004-D-0500
Online at
In writing to the Division of Dockets Management
Docket #FDA-2004-D-0500
(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)

42. Thank you!

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

44. Presentation Outline 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

45. Background
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

46. Background (cont’d)
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

47. Background (cont’d)
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)

48. Why is the draft guidance important?
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)

49. Why is the draft guidance important?
Biggest change from OPDP perspective: the draft guidance facilitates acceptance of eCTD submissions using the new M1 as of June 15, 2015

50. Benefits to Submission in eCTD
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

51. Benefits to Submission in eCTD (cont’d)
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

52. FDASIA Requirement
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.

53. Consistent with Presidential Directive

54. Promotional Materials under Section 745A(a)
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

55. When ‒ timeline for submissions in eCTD
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

56. How to submit 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

57. Overview of M1 Promotional Material Section

58. What have we learned so far?
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

59. What tips have we learned?
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

60. Tips (cont’d)
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 is dedicated to correspondence for promotional materials.

61. Tips (cont’d)
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)

62. Tips (cont’d)
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 is required (along with current product labeling in Section ).

63. Tips (cont’d)
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)

64. Tips (cont’d)
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.

65. CDER Resources
Firms are encouraged to submit sample promotional submissions. To begin the process, the Electronic Submission Support Team at
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

66. Who to contact in CDER
address for questions regarding the draft guidance or eCTD submissions to OPDP:
address for general submission questions for OPDP:
address for technical questions about eCTD:

67. OPDP Contact Information
Building 51 on White Oak Campus
Suites 3200 & 3300
Fax numbers
(301) or (301)
Telephone number
(301)
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

68. Thank you!

69. Questions? ? ? ?