This presentation was initially delivered at the NJ/NY RAPS chapter on November 19, 2015. It reviews the FDA guidance on providing ad-promo submissions in electronic and print formats, explains the complex nature of the guidance and its scope, and includes the latest from FDA on how the guidance is being implemented.

1.
Getting Ad-Promo on
Board the eCTD Train
Presented by:
Dale Cooke
PhillyCooke Consulting
DCooke@PhillyCooke.com
19 November 2015

2. Disclosure: PhillyCooke Consulting is not a law
firm, and nothing provided in this presentation
should be construed as offering legal advice.
Specific details of each company’s promotional
efforts might require adjustments of the
information provided in this presentation.

3. PhillyCooke Consulting helps companies
communicate about FDA-regulated products
using 21st century tools, while remaining
compliant with regulations written in the 1960s.
PhillyCooke Consulting services focus on
1. Review & Approval Process Improvement
2. Training
3. Promotional Review of Tactics
4. Policy Development
5. Agency Submission Preparation

4. Topics
1.Background
2.Guidance Requirements
3.Launch Submissions
4.Paper Submissions
5.Material Types
6.Tips from FDA
7.Next Steps
4

5. Background

6. Move to Electronic Submissions
‣ As part of FDASIA, Congress authorized FDA to
mandate that certain submissions to FDA be
electronic, such as
• NDAs
• INDs
• BLAs
• ANDAs
‣ FDA has been releasing multiple guidances
about different types of submissions
6
Providing Regulatory Submissions in Electronic Format —Certain Human Pharmaceutical Product
Applications and Related Submissions Using the eCTD Specifications available at
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
UCM333969.pdf

7. The CTD of eCTD
7

8. eCTD Format
‣ An XML file structure for submissions to
regulatory authorities*
‣ Establishes a common table of contents for
information
‣ Module 1 (of 5) is used as a catch-all
‣ Promotional submissions use Module 1
8
*For more on eCTD, see http://www.fda.gov/Drugs/DevelopmentApprovalProcess/
FormsSubmissionRequirements/ElectronicSubmissions/ucm153574.htm

9. Guidance Requirements

10. Submitting Ad/Promo Materials
‣ CBER/APLB has been accepting electronic
submissions via portal for years
‣ CDER/OPDP now accepts electronic
submissions via portal, as of June 15, 2015
• Guidance for Industry: Providing Regulatory Submissions in
Electronic and Non-Electronic Format—Promotional
Labeling and Advertising Materials for Human Prescription
Drugs
• Must use version 3.3 or higher of eCTD
10
OPDP Link: http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDER/ucm090181.htm
CBER/APLB Link: http://www.fda.gov/BiologicsBloodVaccines/Development
ApprovalProcess/AdvertisingLabelingPromotionalMaterials/ucm118171.htm

11. 11
April 2015
http://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/UCM443702.pdf

12. A Guidance Like Few Others
“FDA guidances ordinarily contain standard language
explaining that guidances should be viewed only as
recommendations unless specific regulatory or statutory
requirements are cited. FDA is not including this standard
language in this guidance because it is not an accurate
description of all of the effects of this guidance. This
guidance contains both binding and nonbinding
provisions. Insofar as this guidance specifies the format for
electronic submissions pursuant to section 745A(a) of the
FD&C Act, it will have binding effect.”
—page 3
12

13. Guidance Scope
The guidance covers ALL submissions of
promotional materials to OPDP & APLB*
Two types of submissions
1. Mandatory (final samples, subpart H & E)
2. Non-mandatory (DTC TV (for now), advisory
comment, etc.)
13
* CDRH & CVM are not covered by this guidance. CDRH does not require
promotional materials submissions.

14. Mandatory Submissions
For mandatory submissions, some (but not all)
aspects of this guidance will become binding two
years from the date of issuance of the final
version of the guidance
Binding aspects
‣ File formats
‣ File nomenclature
Non-binding aspects
‣ Particular recommendations about FDA’s preferences
14

15. Non-mandatory Submissions
‣ For non-mandatory submissions, all parts of this
guidance will be non-binding
‣ It is highly recommended that companies adopt
these practices
‣ These practices should NEVER be used for
competitor promotion complaints
15

16. All Promo Submissions
Requirements
1. Include NDA, ANDA, or BLA number of
product(s) being promoted
2. Specific material type from 2253 list
3. Separate HCP and consumer material
submissions
4. Separate different submission types (e.g.,
final samples vs. advisory comments)
5. Submit ads and promo labeling separately
from other submissions (e.g., NDAs,
postmarketing reports) 16

17. Mandatory Submissions
All submissions mandated by 505(b), (i), or (j) of
FDCA & 351(a) or (k) of PHS
1. Final samples (2253 submissions)
2. Subpart H (& E) preapproval submissions
3. Subpart H (& E) 30-day submissions
17

18. Overview of 1.15 Organization
18

19. OPDP vs. APLB Discrepancies
‣ Because APLB has been accepting gateway
submissions for years, can use older versions of
eCTD
‣ Both OPDP & APLB can accept version 3.3 or
higher of us-regional-backbone file
‣ For OPDP, Form 2253 ONLY accompanies final
samples
‣ For APLB, Form 2253 accompanies both draft &
final samples
‣ Consequently, must fill out box 14 for APLB
submissions, but not for OPDP
19

20. 20

21. 21

22. Final Samples Suggestion
“Firms are also encouraged to submit annotated versions of
the promotional material(s) cross-referenced to the product
labeling and references, if applicable.”
—Guidance for Industry: Providing Regulatory Submissions
in Electronic and Non-Electronic Format—
Promotional Labeling and Advertising Materials
for Human Prescription Drugs FDA 2015, page 6
22
Though the submission of the
2253 final samples
via eCTD is mandatory,
this change is not.

23. TV Prereview
‣ FDA permitted to mandate 45-day
predissemination submission under 503C of
FDCA
‣ Not subject to mandatory eCTD submission
‣ 2012 predissemination guidance NOT
implemented
‣ 2015 promo submissions guidance directs to that
2012 guidance
23

24. Prereview of Television Ads
‣ FDAAA authorizes FDA to mandate
submission of the FINAL TV spot 45 days
prior to use (in addition to 2253 filing)
‣ FDA draft guidance on implementation
released
• Draft guidance should NOT be followed
• Draft did not require ALL TV spots be submitted
• Prioritized first TV spots, products with
enforcement actions
24
http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDER/ucm090159.htm

25. PhRMA Guidelines on Prereview
Although FDAAA 45-day requirement has NOT
been implemented, PhRMA Guidelines state:
“Principle 8: Companies should submit all new DTC
television advertisements to the FDA before releasing these
advertisements for broadcast.”
Q&A on Principle 8:
“…Under Principle 8, while not intending to place additional
burdens on FDA, companies commit to submitting new DTC
television advertisements to FDA earlier than currently
required and a reasonable time in advance of first use to
give FDA the opportunity to comment, consistent with its
priorities and resources…”
25

26. Non-mandatory eCTD
Submissions
1. Requests for advisory comments
a. Launch
b. Non-launch
2. Follow-up to advisory comments
a. Resubmissions
b. General correspondence
c. Amendments
d. Withdrawal requests
e. References (previously missing)
3. Response to FDA action
a. Untitled and warning letters
b. Requests for information
26

27. Non-mandatory eCTD
Submissions
‣ It will be permissible to continue these
submissions in paper, even after the
guidance is finalized
‣ FDA “strongly encourage[s]” companies to
adopt eCTD even for these submissions
27

28. Complaints
Do NOT submit
complaints about
competitor’s promotion
via eCTD
28

29. Launch Submissions

30. NDA
Filed
NDA
Accepted
Establishes
PDUFA Date
PDUFA Date
10 (or 6) months
after NDA
acceptance
Standard Drug Approval Timeline
Day of Approval
(DOA)
FDA Advisory
Comments
Submission
FDA Advisory
Comments
Received
(~45 days later) Signify
Voluntary
Events

31. FDA Guidance on Launch
Comments
Core launch materials defined as
1. One HCP promo (e.g., vis aid) 12 pages or less
2. One HCP advertisement (e.g., journal ad) 4 pages
or less (excluding brief summary)
3. One DTC promo (e.g., patient brochure) 12 pages
or less
4. One DTC advertisement (e.g., print ad) 4 pages or
less (excluding brief summary)
5. HCP and/or DTC website 12 pages or less (each)
Guidance for Industry: Providing Regulatory Submissions in Electronic and Non-Electronic Format—
Promotional Labeling and Advertising Materials for Human Prescription Drugs FDA 2015, pages 8-9
31

32. Subpart H (& E) Approvals
“FDA may grant marketing approval for a new drug [or biological]
product on the basis of adequate and well-controlled trials
establishing that the drug [or biological] product has an effect on a
surrogate endpoint that is reasonably likely, based on
epidemiologic, therapeutic, pathophysiologic, or other evidence, to
predict clinical benefit or on the basis of an effect on a clinical
endpoint other than survival or irreversible morbidity.”
– Guidance for Industry Fast Track Drug Development Programs –
Designation, Development, and Application Review, FDA 2006, page 3
“The [subpart H or E approval] does not apply to a product alone,
but applies to a combination of the product and specific indication
for which it is being studied.”
– Guidance for Industry Fast Track Drug Development Programs –
Designation, Development, and Application Review, FDA 2006, page 3
32

33. NDA
Filed
NDA
Accepted
Establishes
PDUFA Date
PDUFA Date
10 (or 6) months
after NDA
acceptance
Subpart H (or E) Drug Approval Timeline
Day of Approval
(DOA)
FDA Advisory
Comments
Received
Signify
Voluntary
Events
FDA Advisory
Comments
Submission
(Mandatory)
90 Days Post
Approval
(Begin 30-day
submissions)
Initial 120-
Marketing Period
Ends
Subpart H
Restrictions
Lifted

34. Paper Submissions

35. 35—page 16

36. 36

37. Material Types

38. eCTD Elements
Section VI of guidance provides directions for
specific submission eCTD procedures for all
submission types, including
‣ File structures
• Where to include product label
• Where to include the annotated file (when applicable)
‣ File naming conventions
‣ Attributes
‣ How to submit multiple materials together
‣ Leaf titles and how to make them informative for reviewers
38

39. Presentation of Materials
Section VII of guidance provides directions and
examples for specific types of promotional
materials
Overarching considerations include
‣ Legibility
‣ Comprehensibility
• Annotate as needed to explain what it is, actual sizes,
functionality, etc.
‣ Comprehensive
• Fully functioning websites requested (“whenever possible”)
• All possible permutations and views (e.g., all possible two-
page spreads of a three-page brochure)
39

40. Special Considerations
‣ Materials requiring manipulation
‣ Multi-page spreads
‣ Kits
40

41. Electronic Materials
‣ Submission should represent “how the
promotional piece will look and convey
messages to the end user”
—page 30
‣ FDA requests that the materials be fully
interactive, just like the original
‣ FDA suggests submitting a video as an
alternative
41

42. Tips from FDA

43. eCTD Submissions Happening
‣ New M1 was released June 15, 2015
‣ Some companies have already begun submitting
to OPDP in eCTD
‣ At Food & Drug Law Institute Advertising &
Promotion conference, FDA presented on
lessons learned so far
43

44. Tip 1: Use version 3.3+ of eCTD
‣ OPDP can ONLY accept submissions in version
3.3 or higher
‣ APLB can accept older versions of eCTD
‣ APLB will STOP accepting older versions 24
months after guidance is finalized
44

45. Tip 2: Ad-Promo Correspondence
‣ Do NOT include correspondence related to ad-
promo in other sections (e.g., Section 1.2)
‣ Section 1.15.1 is dedicated solely to ad-promo
correspondence
45

46. Tip 3: Use Correct Date Format
‣ The date format to be used is yyyymmdd (four-
digit year, two-digit month, and two-digit day)
E.g., 20151119
46

47. Tip 4: Annotated Versions Optional
‣ For final sample submissions, annotated
versions are helpful, but not required
‣ Required elements for final samples
• Clean version (Section 1.15.2.1.1)
• Current label (Section 1.14.6)
• Completed Form 2253 (Section 1.1)
For multiple products, include leaf with Form 2253
47

48. Tip 5: Handling JV Relationships
When there is a joint venture partnership, license
holder should send general correspondence
explaining the partnership
‣ Subsequent submissions should note that
partnership (e.g., in comments on Form 2253)
‣ Both companies should use the same version of
eCTD
‣ Coordinate numbering sequencing among the
companies to avoid duplicate submissions
48

49. Tip 6: Use Correct 2253 Version
‣ Use of older versions of Form 2253 can delay
processing
‣ Current version of Form 2253 always available
from FDA forms website:
http://www.fda.gov/AboutFDA/
ReportsManualsForms/Forms/default.htm
49

50. Next Steps

51. Timeline
Guidance is draft
Comment period closed July 21, 2015
‣ Comments can always be submitted on any guidance (draft
or final), but comments received prior to close of comment
period are guaranteed to be considered in subsequent
versions of guidance
‣ Six comments were filed and can be viewed at:
http://www.regulations.gov/#!
docketBrowser;rpp=25;po=0;dct=PS;D=FDA-2015-
D-1163;refD=FDA-2015-D-1163-0001
Two years (24 months) from issuance of final
guidance, SOME aspects of this guidance will be
mandatory
51

52. In the Meantime…
‣ Review your existing submissions standards
against the standards proposed in the guidance
‣ Determine the feasibility of adopting FDA’s
recommendations
‣ Talk with vendors (e.g., review systems) and
internal operations about adopting eCTD
‣ Develop and implement transitional measures
(e.g., adopting file naming conventions)
‣ File comments with FDA
‣ Train marketing ops personnel on eCTD
52

53. Questions?
Dale Cooke
PhillyCooke Consulting
DCooke@PhillyCooke.com
@PhillyCooke on Twitter
PhillyCooke.com
www.Scribd.com/Dale_Cooke
www.slideshare.net/PhillyCooke
53

54. Speaker Bio: Dale Cooke
Dale Cooke is the owner of PhillyCooke Consulting, which provides advice and training to
companies about developing compliant promotional materials for FDA-regulated products. Dale
has worked with more than 30 pharmaceutical and medical device clients around the world. His
insights have been featured in the Wall Street Journal’s Health blog, The Pink Sheet, MedAdNews,
PharmExec, and others. Dale is an active member of the Regulatory Affairs Professionals Society
(RAPS), Drug Information Association (DIA), Food and Drug Law Institute (FDLI), and the Alliance
for a Stronger FDA. He also serves on the faculty of the University of California San Francisco’s
American Course in Drug Development and Regulatory Sciences program.
Dale is the author of Effective Review and Approval of Digital Promotional Tactics, which is part of
FDLI’s primer series. He is regularly invited to speak at industry conferences on topics including
FDA enforcement trends, best practices for review processes, global review practices, and life
sciences use of social media. Previously, Dale served as the head of Regulatory for Digitas Health
LifeBrands, which is part of the Publicis Healthcare Communications Group.
Dale earned his B.A. in Philosophy from Southern Methodist University, an M.A. in Analytical
Philosophy from the University of Arizona, and studied Epidemiology and Biostatistics at Drexel
University’s School of Public Health and Healthcare Compliance at Seton Hall University’s School
of Law.
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