Providing Regulatory 
Submissions in Electronic and 
Non-Electronic Format  
Promotional Labeling and 
Advertising Materials for 
Human Prescription Drugs 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
April 2022 
Electronic Submissions 
Revision 1 
 
OMB Control No. 0910-0001 
Current expiration date available at https://www.reginfo.gov 
 (Search ICR and enter OMB control number 0910-0001) 
See additional PRA statement in section VIII of this guidance.
10366535fnlrv1PRAupdate04-21-23.docx   
Providing Regulatory 
Submissions in Electronic and 
Non-Electronic Format  
Promotional Labeling and 
Advertising Materials for Human 
 
Prescription Drugs
 
Guidance for Industry 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
April 2022 
Electronic Submissions 
Revision 1 
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Electronic Submissions to FDA Under Section 745A(a) of the Federal Food, Drug, and 
Cosmetic Act ........................................................................................................................................... 2 
B.  Promotional Labeling and Advertising ........................................................................................ 4 
III.  GENERAL CONSIDERATIONS ................................................................................... 4 
IV.  CONTENT FOR SPECIFIC TYPES OF SUBMISSIONS ........................................... 5 
A.  Promotional Materials Submitted in Fulfillment of the Postmarketing Reporting 
Requirements (Form FDA 2253 Submissions) ..................................................................................... 6 
B.  Presubmission of Promotional Materials for Accelerated Approval Products ........................ 7 
C.  Promotional Materials Submitted Voluntarily for Advisory Comments ................................. 8 
1. Requests for Comments on Draft Promotional Materials Other Than DTC TV Ads Under 21 CFR 
202.1(j)(4) ............................................................................................................................................ 8 
2. Requests for Comments on Proposed DTC TV Ads Under 21 CFR 202.1(j)(4) ............................ 10 
D.  Resubmissions .............................................................................................................................. 11 
E.  General Correspondence ............................................................................................................. 12 
F.  Amendments (Submission of Previously Missing or Rejected Materials) .............................. 13 
G.  Withdrawal Requests................................................................................................................... 14 
H.  Response to Untitled Letter or Warning Letter ........................................................................ 16 
I.  Response to Information Request ............................................................................................... 16 
J.  Reference Document .................................................................................................................... 16 
K.  Complaints .................................................................................................................................... 17 
V.  FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS IN 
PAPER COPY ............................................................................................................................. 17 
A.  Submitting Paper Copy Promotional Materials to OPDP ....................................................... 19 
B.  Submitting Paper Copy Promotional Materials to APLB........................................................ 19 
VI.  FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS 
ELECTRONICALLY................................................................................................................. 20 
A.  Submission-Description Element ................................................................................................ 21 
B.  Submission-Type and Submission-Sub-Type ............................................................................ 21 
C.  Form Element ............................................................................................................................... 23 
D.  Promotional Audience Type ........................................................................................................ 24 
E.  Correspondence Related to Promotional Materials (Section 1.15.1) ...................................... 24 
i 
  Contains Nonbinding Recommendations 
 
F.  Materials (Section 1.15.2) ............................................................................................................ 26 
1. Attributes ........................................................................................................................................ 26 
2. Clean Version of Materials Submitted (Section 1.15.2.1.1) ........................................................... 27 
3. Annotated Version of Promotional Materials (Section 1.15.2.1.2) ................................................ 27 
G.  Product Labeling (Section 1.14.6 and Section 1.15.2.1.3) ......................................................... 28 
1. Product Labeling Accompanying Form FDA 2253 Submissions (Section 1.14.6) ........................ 28 
2. Annotated Product Labeling (Section 1.15.2.1.3) .......................................................................... 28 
H.  Annotated References (Section 1.15.2.1.4) ................................................................................. 28 
I.  Including Multiple Promotional Materials in One Submission ............................................... 29 
J.  Submission of Promotional Materials Referencing More Than One Application (Grouped 
Submissions) .......................................................................................................................................... 30 
K.  Leaf Titles ..................................................................................................................................... 30 
L.  Use of Operator Attributes ......................................................................................................... 31 
VII.  PRESENTATION ISSUES ............................................................................................ 31 
A.  General Presentation Considerations......................................................................................... 31 
B.  Visibility of Text and Images ...................................................................................................... 32 
C.  Concise Description of Use .......................................................................................................... 32 
D.  Layout Indicators ......................................................................................................................... 33 
E.  Websites, Electronic Interactive Programs, and Electronic Detail Aids ................................ 33 
F.  Materials Requiring Physical Manipulation by the End User ................................................. 34 
G.  Three-Dimensional Promotional Materials ............................................................................... 34 
H.  Multi-Page Spreads ...................................................................................................................... 35 
I.  Kits ................................................................................................................................................ 35 
J.  Dimensions .................................................................................................................................... 35 
K.  Examples of Appropriately Submitted Promotional Materials ............................................... 35 
VIII.  PAPERWORK REDUCTION ACT OF 1995 .............................................................. 37 
ii 
  Contains Nonbinding Recommendations 
 
1  Providing Regulatory Submissions in Electronic and Non-Electronic 
2  Format  Promotional Labeling and Advertising Materials for 
3  Human Prescription Drugs 
4  Guidance for Industry1 
5   
6   
7  This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
8  this topic.  It does not establish any rights for any person and is not binding on FDA or the public.2  You 
9  can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
10  To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
11  title page. 
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This guidance pertains to submissions of promotional materials for human prescription drugs 
18  (drugs)3 to the Food and Drug Administration (FDA or Agency) made by manufacturers, 
19  packers, and distributors (firms), whether the applicant or an entity acting on behalf of the 
20  applicant.  Specifically, this guidance pertains to submissions made to the Office of Prescription 
21  Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) and the 
22  Advertising and Promotional Labeling Branch (APLB) in the Center for Biologics Evaluation 
23  and Research (CBER).  This guidance also explains certain aspects of electronic submission of 
 
1 This guidance has been prepared by the Office of Prescription Drug Promotion (OPDP) in the Center for Drug 
Evaluation and Research (CDER) in cooperation with the Advertising and Promotional Labeling Branch (APLB) in 
the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA).  You may 
submit comments on this guidance at any time.  Submit comments to Docket No. FDA-2015-D-1163 (available at 
https://www.regulations.gov/docket/FDA-2015-D-1163). 
 
2 This sentence does not apply to the discussion regarding the format for electronic submissions under section 
745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). 
 
3 The recommendations in this guidance apply to biological products that are approved for marketing under section 
351 of the Public Health Service Act (PHS Act) and that also meet the definition of drug under section 201(g) of 
the FD&C Act.  For such products, the provisions of the FD&C Act applicable to drugs also apply, as well as the 
regulations implementing these provisions, except that a biological product licensed under section 351 of the PHS 
Act is not required to have an approved new drug application under section 505 of the FD&C Act (21 U.S.C. 355).  
See section 351(j) (42 U.S.C. 262(j)) of the PHS Act.  Therefore, references to drugs in this guidance also include 
human biological products that fall within the definition.  However, this guidance does not apply to those devices 
that CBER regulates as biological products under section 351 of the PHS Act.  These submissions are subject to the 
requirements under section 745A(b) of the FD&C Act.  The electronic submission requirements of section 745A(b) 
fall outside the scope of this guidance and are not discussed in this guidance.  We note, however, that FDA issued 
the guidance for industry and FDA staff eCopy Program for Medical Device Submissions (December 2015) that 
implements the electronic copy provisions of section 745A(b) for medical device submissions to FDA.  We update 
guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA guidance web 
page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.  
  1  Contains Nonbinding Recommendations 
 
24  promotional materials in module 1 of the electronic common technical document (eCTD), using 
25  version 3.3 or higher of the us-regional-backbone file. 
26   
27  For the purpose of this guidance, the term promotional materials collectively refers to 
28  promotional labeling and advertising materials, regardless of the format, manner, or medium by 
29  which they are presented.  Promotional materials may include, but are not limited to, television 
30  advertisements (ads), brochures, booklets, detailing pieces, internet websites, print ads, exhibits, 
31  sound recordings, and radio ads. 
32   
33  The contents of this document do not have the force and effect of law and are not meant 
34  to bind the public in any way, unless specifically incorporated into a contract.  This 
35  document is intended only to provide clarity to the public regarding existing requirements 
36  under the law.  FDA guidance documents, including this guidance, should be viewed only 
37  as recommendations, unless specific regulatory or statutory requirements are cited.  The 
38  use of the word should in Agency guidance means that something is suggested or 
39  recommended, but not required. 
40   
41  An exception to that framework derives from section 745A(a) of the Federal Food, Drug, and 
42  Cosmetic Act (FD&C Act), wherein Congress granted authorization to FDA to require that 
43  submissions under section 505(b), (i), or (j) of the FD&C Act and submissions under section 
44  351(a) or (k) of the Public Health Service Act (PHS Act) be submitted in an electronic format 
45  specified by FDA through guidance.  Accordingly, insofar as this guidance requires that 
46  submissions under section 505(b), (i), or (j) of the FD&C Act and submissions under section 
47  351(a) or (k) o33f the PHS Act be submitted in electronic format specified by FDA, this 
48  document is not subject to the usual restriction in FDAs good guidance practice regulations that 
49  guidances not establish legally enforceable responsibilities.4  Therefore, the portion of this 
50  guidance that establishes the requirement for electronic submissions under section 745A(a) of the 
51  FD&C Act has binding effect, as indicated by the use of the words must, shall, or required.   
52   
53   
54  II.  BACKGROUND 
55   
56  A.  Electronic Submissions to FDA Under Section 745A(a) of the Federal Food, 
57  Drug, and Cosmetic Act 
58   
59  Section 745A(a) of the FD&C Act, added by section 1136 of the Food and Drug Administration 
60  Safety and Innovation Act (FDASIA) (Public Law 112-144), requires that submissions under 
61  section 505(b), (i), or (j) of the FD&C Act and submissions under section 351(a) or (k) of the 
62  PHS Act be submitted in electronic format specified by FDA beginning no earlier than 24 
63  months after FDA issues a guidance specifying such electronic submission format.  Certain types 
64  of promotional-material-related submissions discussed in this guidance are submissions under 
65  subsection (b), (i), or (j) of section 505 of this Act or subsection (a) or (k) of section 351 of the 
66  Public Health Service Act and are, therefore, subject to the requirements of section 745A(a).  
67  Specifically, this includes the following: 
 
4 See 21 CFR 10.115(d). 
  2  Contains Nonbinding Recommendations 
 
68   
69    Postmarketing submissions of promotional materials using Form FDA 2253 (required by 21 
70  CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4)) 
71   
72    Submissions of promotional materials for accelerated approval products (required by section 
73  506(c)(2)(B) of the FD&C Act, 21 CFR 314.550, and 21 CFR 601.45) and other products 
74  where such submissions are required for approval5 under section 505(b), (i), or (j) of the 
75  FD&C Act    
76   
77  The guidance for industry Providing Regulatory Submissions in Electronic Format  
78  Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (December 
79  2014) (the 745A(a) Implementation Guidance) sets forth general information on how FDA 
80  interprets and intends to implement the electronic submission requirements of section 745A(a) of 
81  the FD&C Act.  The 745A(a) Implementation Guidance states that it is not feasible to describe 
82  and implement the electronic format(s) that would apply to all the submissions covered by 
83  section 745A(a) in one guidance document.  Instead, FDA will periodically issue guidances 
84  specifying the electronic format for certain types of submissions.  The guidance for industry 
85  Providing Regulatory Submissions in Electronic Format  Certain Human Pharmaceutical 
86  Product Applications and Related Submissions Using the eCTD Specifications (April 2018) (the 
87  eCTD Guidance) specifies the general format for certain types of electronic submissions using 
88  the eCTD, including the specifications for module 1.6  
89   
90  In addition to the more general information and implementation timeline found in those 
91  guidances, this guidance provides additional information regarding the format to use for 
92  electronic submission of promotional labeling and advertising materials, using the eCTD.  
93  Accordingly, 24 months after the issuance of this guidance, firms will be required to submit 
94  electronically all promotional submissions that fall within the scope of section 745A(a) as 
95  specified in this guidance.  As of that date, paper copies will no longer be accepted for such 
96  submissions.  Note that although only the promotional submissions discussed in sections IV.A 
97  and IV.B that fall within the scope of section 745A(a) will be required to be submitted 
98  electronically in the format specified in this guidance, firms may voluntarily choose to submit 
99  electronically other types of promotional material submissions discussed in this guidance.7   
 
5 In the Federal Register of May 31, 2002 (67 FR 37988), FDA published final regulations (21 CFR 314.640 
(subpart I) and 21 CFR 601.94 (subpart H)) under which the Agency would allow appropriate studies in animals, in 
certain cases, to provide substantial evidence of the effectiveness of new drug and biological products used to reduce 
or prevent the toxicity of chemical, biological, radiological, or nuclear substances.  This rule applies when adequate 
and well-controlled clinical studies in humans cannot be ethically conducted and field efficacy studies are not 
feasible.  Sponsors with products approved under these provisions are subject to similar presubmission requirements 
as accelerated approval products and can use the same procedures outlined in this guidance for submitting 
promotional materials to FDA.   
 
6 The current version of the associated technical specification The eCTD Backbone Files Specification for Module 1 
provides additional information.  See the FDA eCTD website at https://www.fda.gov/ectd. 
 
7 Firms may immediately begin to submit promotional submissions electronically, whether or not the submissions 
fall within the scope of section 745A(a) of the FD&C Act (i.e., it is not necessary to wait until 24 months after the 
issuance of this guidance). 
 
  3  Contains Nonbinding Recommendations 
 
100   
101  This document also discusses types of promotional materials that are not subject to the 
102  mandatory electronic submission requirement in section 745A, (i.e., all promotional materials 
103  discussed in this document other than postmarketing submissions of promotional materials using 
104  Form FDA 2253 and submissions of promotional materials for accelerated approval products, as 
105  discussed in sections IV.C through K of this guidance).   
106   
107  B.  Promotional Labeling and Advertising 
108   
109  Section 201(m) of the FD&C Act defines labeling as all labels and other written, printed, or 
110  graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying 
111  such article (21 U.S.C. 321(m)).8  The U.S. Supreme Court has explained that the language 
112  accompanying such article in the labeling definition is interpreted broadly to include materials 
113  that supplement or explain an article.  No physical attachment between the materials and the 
114  article is necessary; rather, it is the textual relationship between the items that is significant 
115  (Kordel v. United States, 335 U.S. 345, 350 (1948)).   
116   
117  FDA generally recognizes two types of labeling for drugs:  (1) FDA-required labeling and 
118  (2) promotional labeling.  FDA-required labeling is labeling that is necessary to fulfill the 
119  minimum requirements of the FD&C Act and its implementing regulations.  For prescription 
120  drugs, the required labeling is the labeling, drafted by the manufacturer, that is reviewed and 
121  approved by FDA as part of a new drug application (NDA), an abbreviated new drug application 
122  (ANDA), or a biologics license application (BLA) (21 CFR 314.50(c)(2), 314.94(a)(8), and 
123  601.2(a)).  Promotional labeling is generally any labeling, other than the FDA-required labeling, 
124  that is devised for promotion of the product.  Examples of materials that may be considered 
125  promotional labeling pieces for prescription drugs are described in 21 CFR 202.1(l)(2).   
126   
127  The FD&C Act does not define what constitutes an advertisement, but FDA regulations provide 
128  several examples including, but not limited to, materials in published journals, magazines, other 
129  periodicals, and newspapers and in advertisements broadcast through media such as radio, 
130  television, and telephone communication systems (21 CFR 202.1(l)(1)). 
131   
132   
133  III.  GENERAL CONSIDERATIONS  
134   
135  All submissions of promotional materials should meet a set of criteria in order to be reviewed by 
136  the Agency.  Firms should ensure that the following information is provided and considerations 
137  are met when submitting promotional materials, regardless of the format in which the materials 
138  are submitted:  
139   
140    Include the appropriate NDA, ANDA, or BLA number.  
141   
142    For OPDP, address submissions that require correspondences to the attention of the OPDP 
143  Project Manager. 
 
8 See 21 CFR 1.3(a). 
  4  Contains Nonbinding Recommendations 
 
144   
145    Use the most specific material type (from Form FDA 2253) to describe the promotional 
146  material that is the subject of the submission (e.g., do not use the code promotional 
147  labeling when another code is available that gives a more specific description of the 
148  promotional material). 
149   
150    Submit different types of promotional material submissions separately (e.g., do not submit 
151  materials on Form FDA 2253 per the requirement in 21 CFR 314.81(b)(3)(i)) together with 
152  a voluntary request for advisory comments9 on launch materials).  
153   
154    Submit promotional materials separately from other types of submissions (i.e., submissions 
155  not related to promotional materials).  
156   
157    Submit promotional materials directed to health care professionals separately from 
158  submissions of promotional materials directed to consumers. 
159   
160  Occasionally, promotional materials may be directed to both consumers and health care 
161  professionals.  In those circumstances, firms should identify the audience type based on the end-
162  user for the bulk of the information.  For example, press releases should be submitted as 
163  consumer-directed materials unless they are specifically intended for health care professionals.  
164  Websites with distinct sections for health care professionals and consumers should be divided 
165  into two separate submissions.  If the website does not have distinct sections for each audience 
166  and is not intended to be directed solely to health care professionals, firms should submit the 
167  entire website as a consumer submission.   
168   
169  In cases where a company that holds the application collaborates with another firm to promote 
170  the drug (e.g., a collaborative marketing agreement where another firm that is not the application 
171  holder disseminates and submits promotional materials based on a contractual agreement with 
172  the application holder), the application holder should send a general correspondence submission 
173  to OPDP or APLB describing the agreement.  In addition, the business relationship should be 
174  indicated in subsequent submissions of promotional materials.   
175   
176   
177  IV.  CONTENT FOR SPECIFIC TYPES OF SUBMISSIONS10 
178   
179  The content of various types of submissions to the Agency relating to promotional materials is 
180  described below and applies to submissions in both eCTD and non-eCTD format.  Also, as 
181  described in section II of this guidance, submissions described below under sections IV.A and 
182  IV.B must be submitted electronically per the requirements in section 745A(a) of the FD&C Act.  
 
9 Reference in this guidance to the voluntary request for advisory comment(s) on proposed promotional materials by 
firms is distinct from and not to be confused with the process identified in 21 CFR 10.85. 
 
10 Please refer to section VI of this guidance for information on how to submit promotional materials in module 1 of 
the eCTD using us-regional-v3-3.dtd or higher.  Note that complaints should not be submitted using this process. 
 
  5  Contains Nonbinding Recommendations 
 
183  The advertising and promotional labeling submissions described below represent the types of 
184  submissions that FDA currently receives.       
185   
186  A.  Promotional Materials Submitted in Fulfillment of the Postmarketing 
187  Reporting Requirements (Form FDA 2253 Submissions) 
188   
189  Under the FD&C Act and FDA's regulations implementing postmarketing reporting 
190  requirements, applicants must submit specimens of mailing pieces and any other labeling or 
191  advertising devised for promotion of the drug product at the time of initial dissemination of the 
192  labeling and at the time of initial publication of the advertisement for a prescription drug product 
193  (21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4)).  Each submission (also referred to as a 2253 
194  submission) is required to be accompanied by a completed fillable Form FDA 2253 (Transmittal 
195  of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use) and is 
196  required to include a copy of the products current professional labeling (21 CFR 314.81(b)(3)(i) 
197  and 21 CFR 601.12(f)(4)).11 
198   
199  The following provides details on submitting promotional materials in fulfillment of 
200  postmarketing reporting requirements.  OPDP and APLB have different procedures, so firms 
201  should pay careful attention to the following information. 
202   
203  Firms are required to include the following: 
204   
205    Form FDA 2253:  Transmittal of Advertisements and Promotional Labeling for Drugs and 
206  Biologics for Human Use.  (For OPDP submissions, submit this form with final promotional 
207  materials only.)  Firms must use the most current version of the fillable Form FDA 2253.12,13 
208   
209    On Form FDA 2253, box titled For CBER Products Only: 
-
210    OPDP:  Do NOT check the Draft or Final boxes.   
o
211    APLB:  Check the Final box only for Final postmarketing submissions. 
o
212   
213    For cases where promotional materials mention multiple products, note the lead 
-
214  application number on Form FDA 2253 and include an attachment that identifies the 
215  other referenced products (e.g., application type and number, trade name, established 
216  name). 
217   
218    Promotional material(s). 
219   
220    Current product labeling. 
 
11 For more information, see the draft guidance for industry Fulfilling Regulatory Requirements for Postmarketing 
Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics (January 
2014).  When final, this guidance will represent FDAs current thinking on this topic.  
 
12 The most current version of Form FDA 2253 and Form FDA 2253 Instructions Supplement can be found at 
https://www.fda.gov/about-fda/reports-manuals-forms/forms. 
 
13 Do not include Form FDA 356h for submissions to OPDP or APLB. 
 
  6  Contains Nonbinding Recommendations 
 
221   
222  Firms are also encouraged, but not required, to submit annotated versions of the promotional 
223  material(s) cross-referenced to the product labeling and references, if applicable. 
224   
225  Professional and consumer materials should be submitted separately and should not include a 
226  cover letter or correspondence.  For 2253 submissions to OPDP, if a drug has multiple approved 
227  indications that are covered by different reviewers in OPDP,14 firms should submit (when 
228  possible) promotional materials that only promote one indication separately from promotional 
229  materials that promote only another indication.  In such cases, firms may choose to communicate 
230  the indication being promoted in the promotional materials in the Comments section of Form 
231  FDA 2253.  
232   
233  B.  Presubmission of Promotional Materials for Accelerated Approval Products 
234   
235  Applicants whose drug products are approved under the accelerated approval framework (section 
236  506(c) of the FD&C Act, 21 CFR 314 (subpart H), and 21 CFR 601 (subpart E)) and applicants 
237  with other products where such submissions are required for approval must submit promotional 
238  materials to OPDP and APLB as required under section 506(c)(2)(B) of the FD&C Act, 21 CFR 
239  314.550, and 21 CFR 601.45.  Under section 506(c)(2)(B) of the FD&C Act, FDA may grant 
240  accelerated approval of a drug product on the condition, among others, that the sponsor submit 
241  copies of all promotional materials related to the product during the preapproval review period 
242  and, following approval and for such period thereafter as the Agency determines to be 
243  appropriate, at least 30 days before dissemination of the materials.  Additionally, there may be 
244  other situations when the Secretary of Health and Human Services15 may establish 
245  presubmission conditions on promotional materials similar to those in place for accelerated 
246  approval products (e.g., section 564(e)(4)(A) of the FD&C Act).  In such situations, like the drug 
247  products approved under the accelerated approval framework, sponsors will be required to use 
248  the format for electronic submission outlined in section VI of this guidance, no earlier than 24 
249  months after publication of this guidance.   
250   
251  According to 21 CFR 314.550 and 21 CFR 601.45, unless otherwise informed by the Agency, 
252  applicants being considered for accelerated approval must submit to the Agency, during the 
253  preapproval review period, copies of all promotional materials, including both promotional 
254  labeling and ads, intended for dissemination or publication within 120 days following marketing 
255  approval (launch).  Under the same regulatory provisions, after 120 days following marketing 
256  approval, unless otherwise informed by the Agency, the applicant must submit promotional 
257  materials at least 30 days before the intended time of initial dissemination of the labeling or 
258  initial publication of the advertisement (non-launch). 
259   
 
14 For information about OPDP reviewer assignments, email the OPDP Project Manager at CDER-OPDP-
RPM@fda.hhs.gov.    
 
15 The authority for this provision has been delegated to FDA. 
  7  Contains Nonbinding Recommendations 
 
260  The submission should include the following: 
261   
262    Correspondence stating that it is a presubmission of promotional material(s) for an 
263  accelerated approval product (Please refer to section VI.E of this guidance for additional 
264  details on what to include in the correspondence.) 
265   
266    A clean version of the draft promotional material(s) that does not include annotations to the 
267  label or references 
268   
269    An annotated copy of the proposed promotional material that clearly identifies the source of 
270  support for each claim (e.g., specific page and lines of the FDA-approved full prescribing 
271  information (PI) or specific page and column/paragraph from other references) 
272   
273    The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or 
274  Medication Guide with annotations cross-referenced to the proposed promotional material 
275   
276    If applicable, annotated references to support product claims not contained in the PI, cross-
277  referenced to the proposed promotional material 
278   
279    If applicable, annotated references to support disease or epidemiology information, cross-
280  referenced to the proposed promotional material 
281   
282  For draft promotional materials submitted to APLB under 21 CFR 601.45, use Form FDA 2253 
283  with box titled For CBER Products Only checked as Draft.  Do not use Form FDA 2253 for 
284  submissions of draft promotional materials for accelerated approval products to OPDP under 21 
285  CFR 314.550 or 21 CFR 601.45. 
286   
287  C.  Promotional Materials Submitted Voluntarily for Advisory Comments 
288   
289  Section 21 CFR 202.1(j)(4) provides firms with a voluntary opportunity to submit promotional 
290  materials to FDA for advisory comment before the dissemination or publication of those 
291  promotional materials.  Firms may request advisory comments on draft promotional materials 
292  and receive comments in writing from the Agency.  Because this process is intended to provide 
293  input before dissemination or publication, if the Agency learns that the materials submitted or 
294  that substantially similar claims or presentations have been disseminated or published
295  including after submission for commentsthe Agency will generally not review the materials 
296  under the voluntary advisory comment process. 
297   
298  1.  Requests for Comments on Draft Promotional Materials Other Than DTC TV Ads 
299  Under 21 CFR 202.1(j)(4) 
300   
301  Launch materials are draft promotional materials that are voluntarily submitted by a firm to 
302  OPDP or APLB during the launch phase (i.e., the first 120 days that an FDA-approved product, 
303  indication, delivery system, formulation, dosage form, dosing regimen, strength, or route of 
304  administration is marketed to the public) for review and comment before dissemination or 
305  publication.  
  8  Contains Nonbinding Recommendations 
 
306   
307  Requesting comments on promotional materials before launch is encouraged.  Review of core 
308  launch materials is a high priority for Agency reviewers.  Core launch materials generally 
309  include the following: 16 
310   
311    One comprehensive promotional labeling piece directed toward professionals (e.g., sales aid, 
312  visual aid, detail aid, or exhibit panel (if there is a major conference within the launch 
313  phase)), limited to 12 or fewer pages  
314   
315    One advertisement directed toward professionals (e.g., journal ad), limited to 4 or fewer 
316  pages, not including the PI or brief summary  
317   
318    One comprehensive direct-to-consumer (DTC) labeling piece (e.g., patient brochure), limited 
319  to 12 or fewer pages  
320   
321    One DTC advertisement (e.g., magazine ad), limited to 4 or fewer pages, not including the 
322  brief summary  
323   
324    A professional and/or DTC product website (limited to 12 printed legible pages each) or 
325  electronic sales aid if it is a derivative (i.e., contains similar claims and/or presentations) of a 
326  comprehensive labeling piece that is also submitted for voluntary advisory comment   
327   
328  Launch materials other than those listed above (e.g., slide kits and materials longer than the page 
329  limits listed above) are considered non-core launch materials.  Non-core launch materials are a 
330  lower priority than core launch materials.  The Agency recommends that firms apply the 
331  Agencys comments on the core materials to non-core materials.  
332   
333  Non-launch materials consist of draft promotional materials that a firm voluntarily submits to 
334  OPDP or APLB for review and comment before their first use in the public domain but after the 
335  launch phase (i.e., after the first 120 days that an FDA-approved product, indication, delivery 
336  system, formulation, dosage form, dosing regimen, strength, or route of administration is 
337  marketed to the public).   
338   
339  In general, the submission should include the following: 
340   
341    Correspondence stating that it is a voluntary request for advisory comments (Please refer to 
342  section VI.E of this guidance for additional details on what to include in the 
343  correspondence.)17 
344   
 
16 FDA may determine that the materials submitted do not meet the definition of core materials if they exceed 
content or page limitations. 
 
17 For draft promotional materials submitted voluntarily to APLB for advisory comment, please use the fillable Form 
FDA 2253 with the box titled For CBER Products Only checked as Draft.  Please do not use Form FDA 2253 
for submissions of draft promotional material submitted voluntarily to OPDP. 
 
  9  Contains Nonbinding Recommendations 
 
345    A clean version of the draft promotional material(s) that does not include annotations to the 
346  label or references 
347   
348    An annotated copy of the proposed promotional material(s) that clearly identifies the source 
349  of support for each claim (e.g., specific page and lines of the PI or specific page and 
350  column/paragraph from other references) 
351   
352    The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or 
353  Medication Guide with annotations cross-referenced to the proposed promotional material 
354   
355    If applicable, annotated references to support product claims not contained in the PI, cross-
356  referenced to the promotional material 
357   
358    If applicable, annotated references to support disease or epidemiology information, cross-
359  referenced to the promotional material 
360   
361  The following are recommendations for voluntarily submitting draft promotional materials
362  other than TV adsfor advisory comments: 
363   
364    Draft promotional materials submitted for comment should be consolidated together into one 
365  submission for each intended audience (i.e., one submission with professional materials and 
366  one submission with consumer materials).   
367   
368    It is also suggested that draft core launch materials be consolidated into a single submission 
369  for each intended audience rather than sending the materials piecemeal in several 
370  submissions over the course of a few days or weeks.   
371   
372    In cases when the firm intends to submit professional and consumer launch core materials at 
373  around the same time, it is suggested that both submissions be sent on the same day.   
374   
375    Likewise, it is suggested that draft non-core launch promotional materials be consolidated 
376  into single submissions for each intended audience to the extent possible.   
377   
378    Submissions of draft DTC TV ads should not be included in submissions with other types of 
379  materials.  (See section VI of this guidance for information on how to submit.)   
380   
381  2.  Requests for Comments on Proposed DTC TV Ads Under 21 CFR 202.1(j)(4)  
382   
383  The submission should include the following: 
384   
385    Correspondence stating it is a voluntary request for advisory comments on a proposed TV ad 
386  (Please refer to section VI.E of this guidance for additional details on what to include in the 
387  correspondence.) 
388   
  10  Contains Nonbinding Recommendations 
 
389    A clean version of the storyboard of the proposed TV ad that does not include annotations to 
390  the label or references 
391   
392    An annotated version of the storyboard of the proposed TV ad that clearly identifies the 
393  source of support for each claim (e.g., specific page and lines of the PI or specific page and 
394  column/paragraph from other references) 
395   
396    The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or 
397  Medication Guide with annotations cross-referenced to the storyboard 
398   
399    Other appropriate documentation if any of the following apply: 
400   
401    Annotated references to support product claims not contained in the PI, cross-referenced 
-
402  to the storyboard  
403   
404    If the advertisement identifies a person as an actual patient (e.g., a spokesperson) or 
-
405  actual health care professional, a signed statement by that person verifying that he or she 
406  has in fact used or prescribed the drug product for the advertised indication and is not 
407  merely an actor or model 
408   
409    Verification, in the form of a signed statement by the translator, that an official 
-
410  translation of a foreign-language TV ad is accurate 
411   
412    Annotated references to support disease or epidemiology information, cross-referenced to 
-
413  the storyboard 
414   
415    Optionally, submissions for advisory review may include a video or animatic of the 
-
416  proposed TV ad (if included, the video or animatic should be in an acceptable file 
417  format18) 
418   
419  Materials unrelated to a proposed TV ad being voluntarily submitted for advisory comment 
420  should not be included in the review package.  However, more than one TV ad proposal for a 
421  particular indication for a product may be submitted in the same submission.   
422   
423  D.  Resubmissions19 
424   
425  After FDA has responded to a voluntary request for advisory comments or has commented on an 
426  accelerated approval presubmission, firms may revise and resubmit draft materials.  
427   
428  In general, the resubmission should include the following: 
 
18 The document on Specifications for File Format Types Using eCTD Specifications is in the eCTD Submission 
Standards on the FDA eCTD website at https://www.fda.gov/ectd. 
  
19 Please note that resubmissions are not to be used for submissions under Form FDA 2253, Transmittal of 
Advertisements and Promotional Labeling for Drugs and Biologics for Human Use. 
 
  11  Contains Nonbinding Recommendations 
 
429   
430    Correspondence stating that it is a voluntary request for advisory comments on a revised 
431  submission (Please refer to section VI.E of this guidance for additional details on what to 
432  include in the correspondence.) 
433   
434    A clean version of the draft promotional material(s) that does not include annotations to the 
435  label or references 
436   
437    An annotated copy of the proposed promotional material that clearly identifies the source of 
438  support for each claim (e.g., specific page and lines of the PI or specific page and 
439  column/paragraph from other references) 
440   
441    The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or 
442  Medication Guide with annotations cross-referenced to the proposed promotional material 
443   
444    If applicable, annotated references to support disease or epidemiology information, cross-
445  referenced to the proposed promotional material 
446   
447    If applicable, annotated references to support product claims not contained in the PI, cross-
448  referenced to the proposed promotional material 
449   
450  E.  General Correspondence 
451   
452  General correspondence includes any correspondence submitted to FDA that may or may not 
453  reference a specific drug product application and that does not fall into one of the other 
454  categories (e.g., 2253 submission, voluntary request for advisory comments).  Please note that 
455  complaints should not be submitted under the category of general correspondence.   
456   
457  Examples of types of correspondence to submit under this category include the following: 
458   
459    Letters in which a firm informs OPDP or APLB of an error that occurred in its promotional 
460  material(s) or activities for its drug product(s) 
461   
462    Safety update letters in which a firm informs OPDP or APLB that it will promptly revise all 
463  of its promotional materials for a particular drug(s), to be consistent with new safety 
464  information added to the product labeling20 
465     
466    General responses to comments from FDA provided in response to advice (voluntary request 
467  for comments or general) when no revised materials are included and there is no further 
 
20 This type of correspondence is not necessary if the firm notifies FDA in another correspondence (e.g., a 
presubmission for accelerated approval products) that it intends to comply with 21 CFR 314.70(a)(4) or 21 CFR 
601.12(a)(4).  If this type of correspondence is submitted, the recommended subject line is General 
Correspondence  Intent to Comply. 
  
  12  Contains Nonbinding Recommendations 
 
468  voluntary request from the firm to FDA for advisory comments (include the Marketing & 
469  Advertising (MA) number)21 
470   
471    Notifications from a firm to FDA that it plans to disseminate or publish promotional 
472  materials for accelerated approval products previously submitted as required under 21 CFR 
473  314.550 or 601.45 before receipt of comments by FDA (e.g., after 30 days for a non-launch 
474  presubmission or after application approval for a launch submission)22 
475   
476    Notifications from a firm regarding agreements with other companies for the promotion of 
477  the product 
478   
479    Notifications from a firm regarding a change in promotional labeling and advertising contact 
480  information 
481   
482  The submission should include the following: 
483   
484    Correspondence stating that it is a general correspondence (Please refer to section VI.E of 
485  this guidance for additional details on what to include in the correspondence.) 
486   
487  F.  Amendments (Submission of Previously Missing or Rejected Materials) 
488   
489  If a previous voluntary request for advisory comments, a presubmission for accelerated approval 
490  product, or a 2253 submission to FDA is missing one or more of the promotional materials listed 
491  in the correspondence or on Form FDA 2253, these materials should be submitted as 
492  amendments.  Amendments may also be submitted if an incorrect document file was included 
493  with a submission in eCTD format.  
494   
495  For voluntary requests for advisory comments, the submission should include the following: 
496   
497    Correspondence stating that it is an amendment that includes accompanying materials that 
498  were previously missing (Please refer to section VI.E of this guidance for additional details 
499  on what to include in the correspondence.) 
500   
501    Promotional material(s) or the correct document that was omitted from a previous submission 
502  to FDA  
503   
 
21 The MA number is the tracking number that CDER uses to identify a submission.  CBER uses the CBER 
secondary number.  When the term MA number is used in this guidance, it refers to both the MA number and CBER 
secondary number, as applicable. 
 
22 Please also refer to section IV.H of this guidance regarding withdrawal requests.  If a firm plans to disseminate or 
publish promotional materials for accelerated approval products submitted as required under 21 CFR 314.550 or 
601.45 without waiting for comments from FDA, the firm should notify OPDP or APLB in a general 
correspondence submission.  If a firm decides that it does not intend to disseminate or publish promotional materials 
for accelerated approval products, the firm should notify OPDP or APLB in a withdrawal request submission.     
  13  Contains Nonbinding Recommendations 
 
504    Annotated copy of the promotional materials that were omitted from a previous submission 
505  to FDA  
506   
507    The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or 
508  Medication Guide with annotations cross-referenced to the proposed promotional material 
509   
510    If applicable, annotated references to support disease or epidemiology information, cross-
511  referenced to the proposed promotional material that was previously omitted from a 
512  submission to FDA 
513   
514    If applicable, annotated references to support product claims not contained in the PI, cross-
515  referenced to the proposed promotional material that was previously omitted from a 
516  submission to FDA 
517   
518  If an incorrect document was included or if FDA notifies a firm that promotional materials are 
519  missing from a previous 2253 submission that was submitted in paper or non-eCTD format, the 
520  firm should resubmit the entire 2253 submission rather than submitting an amendment.  If part of 
521  a non-eCTD 2253 submission is rejected (e.g., a video does not play), the entire 2253 submission 
522  should be resubmitted.   
523   
524  If the 2253 submission was in eCTD format, the firm should submit an amendment and include 
525  the following: 
526   
527    Correspondence stating that it is an amendment that includes accompanying promotional 
528  materials that were previously missing or rejected (Please refer to section VI.E of this 
529  guidance for additional details on what to include in the correspondence.) 
530   
531    Promotional materials that were missing or rejected from a previous submission to FDA 
532  (firm does not need to resubmit the entire 2253 submission)  
533   
534  Example:  A firm voluntarily submits a request for advisory comments on launch 
535  promotional materials, using the eCTD.  The correspondence file states that three 
536  promotional materials are included in the submission along with annotated copies and 
537  references.  However, upon receipt, FDA notes that the actual submission only includes two 
538  promotional materials with annotated copies and references.  FDA notifies the firm that one 
539  promotional material is missing from the submission and provides the MA number.  The firm 
540  should then submit the missing promotional material and the annotated copy and references 
541  as an amendment, using the eCTD.  The subject line of the correspondence should note that 
542  the submission is an amendment and include the MA number. 
543   
544  G.  Withdrawal Requests 
545   
546  A firm may request to withdraw a previous submission to FDA.  No materials are submitted with 
547  such a request.  
548   
  14  Contains Nonbinding Recommendations 
 
549  Because submission of promotional materials for accelerated approval products is required under 
550  21 CFR 314.550 and 601.45, firms should only use a withdrawal request for such materials if the 
551  firm does not plan to disseminate or publish the promotional materials.23 
552   
553  The submission should include the following: 
554   
555    Correspondence stating that it is a withdrawal request (Please refer to section VI.E of this 
556  guidance for additional details about what to include in the correspondence.) 
557   
558  Example 1:  A firm voluntarily submits draft promotional materials for advisory review for 
559  its product (not approved under the accelerated approval regulations at 21 CFR 314.510 or 
560  601.41) and later decides to disseminate the promotional materials without waiting for FDA 
561  comments.  The firm should notify FDA of its intent to withdraw the request for comments.  
562  The subject line of the correspondence should note that the submission is a withdrawal 
563  request and include the date of the request or MA number. 
564   
565  Example 2:  A firm voluntarily submits draft promotional materials for advisory review for 
566  its product (not approved under the accelerated approval regulations at 21 CFR 314.510 or 
567  601.41) and later decides not to disseminate the promotional material.  The firm should 
568  notify FDA of its intent to withdraw the request for comments.  The subject line of the 
569  correspondence should note that the submission is a withdrawal request and include the date 
570  of the request or MA number. 
571   
572  Example 3:  A firm submits draft non-launch promotional materials for its product approved 
573  under the accelerated approval regulations at 21 CFR 314.510 or 601.41 and, two weeks 
574  later, decides that it does not intend to disseminate the promotional material.  The firm 
575  should notify FDA of its intent to withdraw the submission.  The subject line of the 
576  correspondence should note that the submission is a withdrawal request and include the date 
577  of the submission or MA number. 
578   
579  Example 4:  A firm submits final promotional material under cover of Form FDA 2253 in 
580  fulfillment of the postmarketing reporting requirements and subsequently decides that it will 
581  never disseminate the promotional material.  The firm should immediately notify FDA of its 
582  intent to withdraw the 2253 submission by submitting a correspondence.  The subject line of 
583  the correspondence should note that the submission is a withdrawal request and include the 
584  date of the submission or MA number.  Please refer to section VI.E of this guidance for 
585  additional details about what to include in the correspondence. 
586   
 
23 Please also refer to section IV.F of this guidance regarding general correspondence.  If a firm plans to disseminate 
or publish promotional materials for accelerated approval products submitted as required under 21 CFR 314.550 or 
601.45 without waiting for comments from FDA, the firm should notify OPDP or APLB in a general 
correspondence submission.  If a firm decides that it does not intend to disseminate or publish promotional materials 
for accelerated approval products, the firm should notify OPDP or APLB in a withdrawal request submission.     
  15  Contains Nonbinding Recommendations 
 
587  H.  Response to Untitled Letter or Warning Letter 
588   
589  A response to an untitled letter or a warning letter is a correspondence type that includes a firms 
590  initial response or additional correspondence pertaining to an untitled letter or warning letter 
591  from FDA regarding promotion.  
592    
593  The submission should include the following: 
594   
595    Correspondence stating that it is a response to an untitled letter or warning letter  This 
596  response may include the firms initial or subsequent responses.  (Please refer to section VI.E 
597  of this guidance for additional details on what to include in the correspondence.) 
598   
599    Corrective piece(s), if applicable 
600   
601  I.  Response to Information Request 
602   
603  FDA may issue a letter of inquiry to firms when investigating potentially violative activity.  The 
604  firms response to a letter of inquiry is considered a response to an information request.  FDA 
605  will notify the firm when a response should be considered a response to an information request.  
606  The correspondence should state that it is a response to an information request.   The 
607  correspondence should include the firms response to the questions and issues raised in FDAs 
608  letter of inquiry, including any materials FDA has requested.  (Please refer to section VI.E of this 
609  guidance for additional details on what to include in the correspondence.) 
610   
611  J.  Reference Document 
612   
613  Reference documents are annotated materials that were missing from a previous submission to 
614  FDA.  Promotional materials that were entirely omitted from a previous submission should not 
615  be included in this type of submission.  (Please refer to section IV.G of this guidance if 
616  promotional materials were entirely omitted from a previous submission.)  
617   
618  The submission should include the following: 
619   
620    Correspondence stating that it is a reference document submission and the specific 
621  information regarding what is in the submission (i.e., annotated references, annotated 
622  promotional materials, and/or annotated labeling)  (Please refer to section VI.E of this 
623  guidance for additional details on what to include in the correspondence.) 
624   
625    Annotated references, annotated promotional materials, and/or annotated labeling 
626   
627  Example:  A firm voluntarily submits a request for advisory comments for non-launch 
628  materials that includes two clean copies of promotional materials.  However, the submission 
629  does not include annotated copies of the promotional materials or annotated references.  FDA 
630  notifies the firm and provides the MA number.  The firm should submit the missing materials 
631  as a reference document.  The subject line of the correspondence should note that it is a 
632  reference document submission and include the MA number. 
  16  Contains Nonbinding Recommendations 
 
633   
634  K.  Complaints 
635   
636  Please note that complaints about prescription drug promotion are not accepted in eCTD format 
637  and should be submitted as either paper copies or in an electronic non-eCTD format.24  Please 
638  submit complaints regarding professional and consumer materials separately.  A duplicate copy 
639  of the submission should be provided.  Please do not include Form FDA 2253 or Form FDA 
640  356h.25 
641   
642  The submission should include the following: 
643   
644    Correspondence stating that it is a complaint  Please include the drug, manufacturer, and 
645  specific regulatory concerns in the correspondence.  In addition, the correspondence should 
646  include the name, title, address, phone, fax, and email of the person that the Agency should 
647  contact about issues related to the submission. 
648   
649    Supporting information or documentation, if available. 
650   
651   
652  V.  FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS IN 
653  PAPER COPY 
654   
655  Paper copies of all promotional submission types will be accepted until 24 months following 
656  publication of this guidance.  When paper copy materials are submitted, sponsors are 
657  encouraged, but not required, to include one non-eCTD copy of the contents of the submission 
658  on a CD and include a statement in the cover letter verifying that the contents of the CD match 
659  the contents of the paper submission.  Please refer to tables 1 and 2 to determine the number of 
660  copies to submit for each submission type.26  Beginning 24 months after this guidance publishes, 
661  paper copies will no longer be accepted for postmarketing submissions made under 21 CFR 
662  314.81(b)(3)(i) or 21 CFR 601.12(f)(4) (see table 2) or for presubmissions of promotional 
663  materials for accelerated approval or other products where such submissions are required for 
664  approval under section 745A(a) of the FD&C Act (see table 1).  (See section VI of this guidance 
665  for further discussion.)   
666   
 
24 If applicable, an electronic copy of a TV or radio ad in an acceptable file format (e.g., a CD containing a .wmv or 
.wma file) may be included with a complaint. 
 
25 Form FDA 356h is titled Application to Market a New or Abbreviated New Drug or Biologic for Human Use. 
 
26 Note that once a firm submits an application-related document in eCTD format including, but not limited to, the 
types of documents described in this guidance, paper copies related to that application should no longer be submitted 
unless specifically requested by the Agency. 
 
  17  Contains Nonbinding Recommendations 
 
667  Please note that complaints are not accepted in the eCTD and should only be submitted as paper 
668  copies.  If any submission is submitted electronically in eCTD format, paper copies should not 
669  also be submitted, unless specifically requested.27   
670    
671  Table 1:  Number of Paper Copies for Various Submission Types Based on Recipient 
Type of Submission  Number of Paper Copies 
If Recipient is OPDP  If Recipient is APLB 
Voluntary advisory  3  2 
submission (not a TV ad) 
Voluntary advisory  10*   2*  
submission of a TV ad 
Presubmission of  3  2 
promotional materials for 
accelerated approval 
products 
503C TV ad  12*    2*  
Resubmission  3  2 
General correspondence  2  2 
Amendment  3  2 
Withdrawal request  2  2 
Response to notice of  2  2 
violation or warning letter 
Response to information  2  2 
request 
Reference document  3  2 
Complaint  2  2 
672  * If a video is provided, only one copy of the video is necessary. 
673   
674  Table 2:  Number of Paper Copies of Promotional Materials to Submit in Fulfillment of the 
675  Postmarketing Reporting Requirements (2253 Submissions)* 
2253 Submissions  Number of Paper Copies 
If the promotional material(s) mentions a single  2 
product 
If the promotional material(s) mentions multiple  3 
products 
676  * The number of copies is the same for OPDP and APLB.  Note that beginning 24 months after publication of this 
677  guidance, under section 745A(a) of the FD&C Act, firms will no longer be able to submit these promotional 
678  materials in paper copy.  
679   
680  OPDP and APLB will continue to accept promotional materials submitted in fulfillment of the 
681  postmarketing reporting requirements (2253 submissions) in electronic, non-eCTD, format (e.g., 
 
27 FDA may request paper copies of a submission if upon receipt of the electronic representation of the promotional 
material it appears to be inadequate to allow FDA to conduct a proper review (e.g., a unique promotional material 
that requires physical manipulation in the hands of the reviewer).  In such cases, FDA will notify the firm of the 
need to submit in paper and the number of copies requested.   
  18  Contains Nonbinding Recommendations 
 
682  CDs) until 24 months after publication of this guidance.  Such submissions do not require 
683  inclusion of a paper copy of the entire submission, except that a signed paper copy of Form FDA 
684  2253 must be included to allow for processing.  Please follow the recommendations in table 2 for 
685  the number of copies to submit. 
686   
687  A.  Submitting Paper Copy Promotional Materials to OPDP 
688   
689  Please send paper copies to the following address: 
690   
691  Office of Prescription Drug Promotion 
692  Food and Drug Administration 
693  5901-B Ammendale Road 
694  Beltsville, MD  20705-1266 
695   
696  For time-sensitive materials, please confirm receipt of the submission with a phone call to the 
697  OPDP project manager at 301-796-1200 or by email at CDER-OPDP-RPM@fda.hhs.gov. 
698   
699  OPDP suggests applying an OPDP sticker or other prominent directional notation to the 
700  exterior of packages submitted to OPDP to help avoid misdirection of promotional materials.  If 
701  it is not possible to add this notation to the exterior of the package, OPDP recommends adding a 
702  prominent directional notation (e.g., sticker, rubber stamp) to the cover letter itself.   
703   
704  B.  Submitting Paper Copy Promotional Materials to APLB 
705   
706  Please send paper copies to the following address: 
707   
708  Advertising and Promotional Labeling Branch, HFM-602 
709  Food and Drug Administration 
710  Center for Biologics Evaluation and Research 
711  Document Control Center 
712  10903 New Hampshire Ave. 
713  WO71  G112 
714  Silver Spring, MD 20993-0002 
715   
716  Any questions for APLB may also be addressed to APLB by phone at 240-402-9158. 
717   
718   
  19  Contains Nonbinding Recommendations 
 
719  VI.  FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS 
720  ELECTRONICALLY28 
721   
722  This section provides information on specific aspects of how to submit promotional labeling and 
723  advertising materials to FDA electronically in eCTD format.29  As discussed in section II of this 
724  guidance, there are two types of submissions related to promotional materials that are 
725  submissions under subsection (b), (i), or (j) of section 505 of [the FD&C] Act or subsection (a) 
726  or (k) of section 351 of the Public Health Service Act and are, therefore, subject to the 
727  mandatory electronic submission requirement in section 745A(a) of the FD&C Act.   
728   
729  The two types of submissions are as follows: 
730   
731  1.  Postmarketing submissions of promotional materials using Form FDA 2253 (required by 
732  21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4)) 
733   
734  2.  Submissions of promotional materials for accelerated approval products (required by 
735  section 506(c)(2)(B) of the FD&C Act, 21 CFR 314.550, or 21 CFR 601.45) and other 
736  products where such submissions are required for approval   
737   
738  This guidance, along with the eCTD Guidance, specifies the electronic format for these 
739  submission types.  Therefore, beginning no earlier than 24 months after publication of this 
740  guidance, firms will be required to submit these types of submissions electronically.  As of that 
741  date, paper copies will no longer be accepted for such submissions.   
742   
743  Although the other types of submissions related to promotional materials discussed in this 
744  guidance are not subject to the mandatory electronic submission requirement in section 745A(a) 
745  of the FD&C Act,30 firms mayand are strongly encouraged tomake such submissions 
746  electronically.  However, paper copies will still be accepted for submission types that do not fall 
747  under section 745A(a).  We note that if firms do choose voluntarily to submit other materials 
748  electronically, CDER is currently only able to accept them in eCTD format using us-regional-v3-
749  3.dtd.31  Once a firm submits an application-related document in eCTD format, including, but not 
750  limited to, the types of documents described in this guidance, paper copies related to that 
751  application should no longer be submitted unless specifically requested by the Agency. 
752   
 
28 Insofar as section VI of this guidance establishes the requirement for electronic submissions under section 
745A(a) of the FD&C Act, it has binding effect. 
 
29 The eCTD module 1 specifications discussed in this section can be located in the eCTD Submission Standards 
on the FDA eCTD website at https://www.fda.gov/ectd. 
 
30 Table 1 (with the exception of presubmissions of promotional materials for accelerated approval products) 
provides a list of the types of submissions that are not subject to the mandatory electronic submission requirement in 
section 745A(a) of the FD&C Act. 
 
31 CBER is able to accept eCTD submissions using previous versions of the us-regional-backbone file until 
24 months after publication of this guidance.    
 
  20  Contains Nonbinding Recommendations 
 
753  In some cases, the company that holds the application for a drug collaborates with another 
754  company to promote the drug.  If the company handling promotion of the drug wants to submit 
755  promotional materials to OPDP or APLB using the eCTD, the company should work with the 
756  application holder to ensure that both companies are using the same version of the us-regional-
757  backbone file.  If the submission is for OPDP, both companies will need to use the same version 
758  (for example, us-regional-v3-3.dtd).  In addition, both companies should work together to come 
759  up with a system for generating sequence numbers in order to avoid the use of duplicate 
760  sequence numbers that will result in a rejection of one of the submissions.  For example, a 
761  company could choose to assign a block of numbers to a particular vendor (e.g., start 
762  promotional submissions with sequence 5000).  
763   
764  Please note that the eCTD format accommodates a wide range of applications and related 
765  submission types other than submissions of promotional materials.  Therefore, a specific 
766  submission may not use all of the possible section-heading elements in each module.  The 
767  following sections describe specific procedures for submitting promotional labeling and 
768  advertising to FDA in eCTD format, including submissions made under section 745A(a) of the 
769  FD&C Act.   
770   
771  A.  Submission-Description Element 
772   
773  The submission-description element is an optional field.  FDA recommends including the 
774  submission-description element to provide a high-level description of the purpose of the 
775  submission and to help differentiate similar types of submissions.  If used, the submission-
776  description element should include the description of the type of submission and materials, the 
777  date of the submission,32 and the MA number (if the MA number has been provided in a 
778  previous communication with FDA). 
779   
780  The following are examples of helpful submission descriptions: 
781   
782    Request for comments on professional launch website, print ad, and sales aid 20140501  
783    Withdrawal request 20140405 for print ad MA61 submitted on 20140115  
784    Response to untitled letter 20140301 MA456 
785    Reference documents for professional launch print ad 20140302 MA31 
786    Consumer 2253 submission 20140915 
787   
788  B.  Submission-Type and Submission-Sub-Type 
789   
790  For all promotional materials submitted to FDA via the eCTD (including promotional materials 
791  submitted in fulfillment of the postmarketing reporting requirements), use the submission-type 
792  Promotional Labeling Advertising.  If promotional materials are submitted in the eCTD 
793  without specifying Promotional Labeling Advertising as the submission-type, the submission 
794  may not be appropriately routed to OPDP or APLB and, as a result, there may be a rejection or 
795  delay in processing and responding to the submission.        
796   
 
32 The date format to be used is yyyymmdd (four-digit year, two-digit month, and two-digit day).   
  21  Contains Nonbinding Recommendations 
 
797  The attribute submission-sub-type is used to further clarify the purpose of the submission.  The 
798  following are the current valid submission-sub-type codes for the submission-type Promotional 
799  Labeling Advertising:  
800   
801    Original  Use this submission-sub-type for all promotional materials submitted in 
802  fulfillment of the postmarketing reporting requirements (2253 submissions) and for materials 
803  that do not have a submission history with FDA.  This includes original promotional 
804  materials such as voluntary requests for advisory comments on launch materials or non-
805  launch materials, and presubmission of promotional materials for accelerated approval 
806  products.  Also use this code for responses to untitled letters, warning letters, and information 
807  requests and for other general correspondence if no submission history with FDA exists for 
808  the materials. 
809   
810    Resubmission  Use this submission-sub-type for voluntary requests for advisory comments 
811  and presubmissions of revised promotional materials that were previously submitted as an 
812  original submission.  Do not use this submission-sub-type for any 2253 submissions.  
813   
814    Amendment  Use this submission-sub-type for a submission that contains additional 
815  supportive material to augment information previously submitted, e.g., the submission of 
816  promotional material that was previously missing or rejected, withdrawal requests, and 
817  submissions of annotated references.  In addition, use this submission-sub-type for responses 
818  to untitled letters, warning letters, and information requests and for general correspondence if 
819  there was an original submission to FDA in eCTD format. 
820   
821  Table 3 summarizes the submission process and the submission-sub-type code for new 
822  submissions.  The submission history is defined by the format through which the original 
823  submission was made.  For example, if a 2253 submission was received in paper format (or on a 
824  CD in non-eCTD format), the entire submission is considered to be paper, and all subsequent 
825  submissions related to the original 2253 submission (amendments, withdrawal requests, etc.) 
826  made prior to the 24 months after publication of this guidance should be made in paper format.  
827  FDA will work with firms to determine the appropriate format for subsequent submissions made 
828  after 24 months of publication of this guidance to a 2253 submission originally received in paper 
829  format.  If a submission is received in eCTD format, all subsequent submissions related to the 
830  submission should be made in eCTD format. 
831   
  22  Contains Nonbinding Recommendations 
 
832  Table 3:  Submission Process and Coding  
Submission History   Action  Code for Submission-Sub-Type 
Has no prior FDA  Submit to the eCTD    Original  
submission history  with the same 
submission-id as the 
sequence number 
All promotional  Submit to the eCTD    Original 
materials submitted  with the same 
in fulfillment of the  submission-id as the 
postmarketing  sequence number 
reporting 
requirements (2253 
submissions) 
Already has an  Submit to the eCTD    Resubmission for resubmissions 
associated eCTD  with the same   
promotional  submission-id as the    Amendment for amendments; 
submission  original promotional  withdrawal requests; reference 
  submission  documents; responses to untitled letters, 
warning letters, and information 
requests; and general correspondence 
Has a paper-copy  Do not submit to the    Resubmissions:  Submit using paper-
submission history  eCTD*  copy process* 
only   
  Amendments; withdrawal requests; 
reference documents; responses to 
untitled letters, warning letters, and 
information requests; and general 
correspondences:  Submit using paper 
copy process.  
833  * FDA will work with firms to determine the appropriate format for subsequent submissions made after 24 months 
834  of publication of this guidance to a 2253 submission originally received in paper format.  If a submission is received 
835  in eCTD format, all subsequent submissions related to the submission should be made in eCTD format. 
836   
837  C.  Form Element 
838   
839  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
840  use form-type Form FDA 2253 (Transmittal of Advertisements and Promotional Labeling for 
841  Drugs and Biologics for Human Use) and submit this form in section 1.1.  For cases where 
842  promotional material(s) mention multiple products,33 include the attachment listing the other 
843  referenced products as a separate leaf title with Form FDA 2253 in section 1.1.34  Do not include 
844  Form FDA 356h for submissions to OPDP or APLB. 
845   
 
33 Please refer to section VI.J of this guidance regarding submitting promotional materials that reference more than 
one application. 
 
34 Please refer to section VI.K of this guidance for a detailed description of leaf titles. 
  23  Contains Nonbinding Recommendations 
 
846  D.  Promotional Audience Type 
847   
848  When providing information in module 1.15, reference the leaves at the lowest heading elements.  
849  For example, the m-1-15-promotional-material heading element needs an attribute of 
850  promotional-material-audience-type.  When a leaf is referenced in any subsection of 
851  module 1.15, provide the attribute as a coded value from its corresponding attribute list 
852  (promotional-material-audience-type.xml).   
853   
854  The current valid codes for promotional-material-audience-type are as follows:  
855   
856    Consumer  for promotional materials directed to consumers  
857    Professional  for promotional materials directed to health care professionals 
858   
859  E.  Correspondence Related to Promotional Materials (Section 1.15.1) 
860   
861  Submit the correspondence relating to promotional materials as an individual portable document 
862  format (PDF) file in the appropriate subsection of 1.15.1.  Firms will need to submit a 
863  correspondence for all submission types listed in section 1.15.1.  A separate cover letter should 
864  not be submitted in section 1.2.  Please note that firms should not submit a correspondence or a 
865  cover letter with 2253 submissions.35  In some cases, the correspondence may be the actual 
866  response and the only file necessary for the submission (e.g., response to untitled letter, response 
867  to an Agency communication, or a general correspondence).  Correspondence submitted to 
868  section 1.15.1 should include the following: 
869   
870    Subject line describing the reason for the submission, the NDA/ANDA/BLA number, the 
871  proprietary name/established name (dosage form), and the name of the TV ads (if applicable) 
872   
873  Examples of acceptable descriptions to be included in the subject line include the following: 
874   
875    Request for Comments on Launch Materials 
-
876    Request for Comments on Non-Launch Materials 
-
877    Presubmission of Launch Promotional Materials for Accelerated Approval Product 
-
878    Presubmission of Non-Launch Promotional Materials for Accelerated Approval Product 
-
879    Response to Untitled Letter 
-
880    Response to Warning Letter 
-
881    Response to Information Request 
-
882    Amendment 
-
883    Withdrawal Request 
-
884    Submission of Annotated References 
-
885    General Correspondence 
-
886   
 
35 If, however, a firm is withdrawing a Form FDA 2253 submission, the firm must submit a correspondence 
withdrawing the submission in section 1.15.1.9. 
  24  Contains Nonbinding Recommendations 
 
887  The body of the correspondence should include the following information:  
888   
889    Regulatory description of the submission.  
890   
891    Statement that the submission is virus free, with a description of the software (name, version, 
892  and company) used to check the files for viruses. 
893   
894    A list of all promotional materials included in the submission, with the material type, 
895  material ID, and description for each item listed. 
896   
897    A concise description of use of the promotional material(s), if applicable.36 
898   
899    Whether the submission is for a launch or non-launch. 
900   
901    If the submission is for a launch, whether the promotional materials are core or non-core. 
902   
903    Whether the submission is subject to the regulations in 21 CFR 314.550 or 21 CFR 601.45. 
904   
905    Whether the submission is a TV ad. 
906   
907    If the submission is the initial response to an untitled letter or warning letter, a list of all 
908  promotional materials (with the 2253 submission date) for the drug product(s) that contain 
909  violations similar to those described in the letter. 
910   
911    Whether the submission contains health-care-professional-directed materials or consumer-
912  directed materials. 
913   
914    Where applicable, whether the Agency has previously commented on the promotional 
915  material(s); the comment date; and the Marketing, Advertising and Communications 
916  Management Information System (MACMIS) number, MA number, or CBER secondary 
917  number.  
918   
919    The name, title, address, phone, fax, and email of the individual the Agency should contact 
920  about issues related to the submission.  If there are separate regulatory and technical points of 
921  contact, please include this information for both individuals. 
922   
 
36 Please refer to section VII.C of this guidance for additional details. 
 
  25  Contains Nonbinding Recommendations 
 
923  F.  Materials (Section 1.15.2)37  
924   
925  1.  Attributes 
926   
927  Submit promotional labeling and advertising materials as individual files in an approved file 
928  format in section 1.15.2.38  When providing information in a subsection of module 1.15.2 
929  materials, three attributes are needed: promotional-material-doc-type, promotional-material-
930  type, and material-id.  An optional attribute, issue-date, should only be provided when the 
931  promotional-material-doc-type is a promotional 2253 submission.39  The attribute promotional-
932  material-doc-type indicates the purpose of the promotional submission and needs to be provided 
933  with the m1-15-2-materials heading element.  Provide the attributes as coded values from their 
934  corresponding attribute list (promotional-material-doc-type.xml).  Table 4 shows the current 
935  valid codes for promotional-material-doc-type.   
936   
937  Table 4:  Promotional Material Document Types and Descriptions 
Promotional Material  Description  
Document Type  
Promotional 2253   Form and materials required from submitter at initial 
dissemination of labeling as well as initial publication of an 
advertisement 
 Request for Advisory Launch   Voluntary submission of launch promotional materials for 
FDA review and comment sent before dissemination or 
publication 
 Request for Advisory Non- Voluntary submission of non-launch promotional materials 
Launch   for FDA review and comment sent before dissemination or 
publication 
Presubmission Accelerated  Promotional materials intended to be used in the first 120 
Launch   days after approval that are submitted to FDA before 
dissemination or publication as required by 21 CFR 314.550 
and 601.45 
Presubmission Accelerated  Promotional materials intended to be used after the 120-day 
Non-Launch   postapproval period that are submitted to FDA before 
dissemination or publication as required by 21 CFR 314.550 
and 601.45 
938   
939  The attribute promotional-material-type indicates the type of media/delivery method of the 
940  promotional material and should be provided with the m-1-15-2-1 material heading element.  
 
37 If including multiple promotional materials in one submission, please refer to section VI.I of this guidance.  If 
submitting promotional materials that reference more than one application, see section VI.J of this guidance. 
 
38 The Specifications for File Format Types Using eCTD Specifications is in the eCTD Submission Standards on the 
FDA eCTD website at https://www.fda.gov/ectd. 
 
39 The date format to be used is yyyymmdd (four-digit year, two-digit month, and two-digit day). 
  26  Contains Nonbinding Recommendations 
 
941  Provide the attributes as coded values from their corresponding attribute list (promotional-
942  material-type.xml).40   
943   
944  The material-id attribute may consist of letters, numbers, or both, and should not exceed 
945  30 characters.  The issue-date attribute, if applicable, should follow the date format as 
946  yyyymmdd (four-digit year, two-digit month, and two-digit day).  
947   
948  2.  Clean Version of Materials Submitted (Section 1.15.2.1.1) 
949   
950  For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 
951  CFR 314.550 or 601.45, submit clean versions of the promotional materials (i.e., versions not 
952  including annotations to the label or references) in section 1.15.2.1.1.   
953   
954  Clean versions of corrective pieces should also be submitted in section 1.15.2.1.1, using the 
955  eCTD replace operation. 
956   
957  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
958  clean final versions of the promotional materials without any annotations must be submitted in 
959  section 1.15.2.1.1.   
960   
961  3.  Annotated Version of Promotional Materials (Section 1.15.2.1.2) 
962   
963  For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 
964  CFR 314.550 or 601.45, submit annotated versions of the promotional materials (i.e., versions 
965  that are cross-referenced to the product labeling and, if applicable, references) in section 
966  1.15.2.1.2. 
967    
968  Annotated versions of corrective pieces should also be submitted in section 1.15.2.1.2, using the 
969  eCTD replace operation. 
970   
971  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
972  firms may choose to submit annotated versions of the promotional materials in section 1.15.2.1.2 
973  that are cross-referenced to the product labeling and, if applicable, references.  References 
974  improve the efficiency of review.  
975   
976  Firms should highlight and annotate the materials with a cross-reference to the product labeling 
977  or references.  When product labeling or other references are used to support a claim or 
978  presentation in proposed promotional materials, hypertext links should be provided in the 
979  annotated promotional material to the specific page that contains the supporting information.  
980   
 
40 The current codes for promotional-material-type, as well as the codes for other attributes, are located in the eCTD 
Submission Standards, on the FDA eCTD website at https://www.fda.gov/ectd. 
  
  27  Contains Nonbinding Recommendations 
 
981  G.  Product Labeling (Section 1.14.6 and Section 1.15.2.1.3) 
982   
983  1.  Product Labeling Accompanying Form FDA 2253 Submissions (Section 1.14.6) 
984   
985  Form FDA 2253 specifies that the most current product labeling accompany the submission.  
986  Firms must submit the most current product labeling, as required in 21 CFR 314.81(b)(3)(i), to 
987  section 1.14.6.  For promotional labeling pieces, this is the PI that accompanies the promotional 
988  materials.  The required format for the PI is PDF.41   
989   
990  2.  Annotated Product Labeling (Section 1.15.2.1.3) 
991   
992  For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 
993  CFR 314.550 or 601.45, include the annotated product labeling in section 1.15.2.1.3.42  Firms 
994  should highlight and annotate, with a cross-reference to the promotional materials, the sections 
995  of the product labeling that are referred to in the promotional materials.  When product labeling 
996  is used to support a claim or presentation in proposed promotional materials, hypertext links 
997  should be provided to the specific page that contains the supporting information.  
998   
999  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
1000  firms may choose to provide the annotated product labeling with hypertext links.43  
1001   
1002  H.  Annotated References (Section 1.15.2.1.4) 
1003   
1004  If references are provided, submit each reference as an individual PDF file and place it in 
1005  section 1.15.2.1.4.  Firms should highlight and annotate, with a cross-reference to the 
1006  promotional materials, the sections of the full reference that are referred to in the promotional 
1007  materials.  When a reference is used to support a claim or presentation in proposed promotional 
1008  materials, firms should provide, in the annotated promotional material, hypertext links to the 
1009  specific page of the reference that contains the supporting information.  
1010   
1011  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
1012  firms may choose to provide references with hypertext links.  References improve the efficiency 
1013  of review.  
1014   
 
41 Firms may choose to submit the current product labeling with each 2253 submission.  Alternatively, once product 
labeling is submitted to section 1.14.6 with a 2253 submission, firms may cross-reference the current product 
labeling within the XML backbone.  If firms choose to reference the current product labeling within the XML 
backbone, they should ensure that the version of the product labeling that is referenced is correct and that the leaf 
title is revised with each 2253 submission to be informative for Agency reviewers (e.g., include the date of 
submission).  Refer to section VI.K of this guidance for recommendations regarding leaf titles.    
 
42 Even if the submission does not include annotations to the label or a part of the label, firms should still include the 
entire label in section 1.15.2.1.3.    
 
43 Annotated labeling submitted in fulfillment of the postmarketing reporting requirements must be included as a 
PDF file in section 1.15.2.1.3.  The current product labeling must still be submitted in section 1.14.6. 
  28  Contains Nonbinding Recommendations 
 
1015  I.  Including Multiple Promotional Materials in One Submission 
1016   
1017  For draft promotional materials voluntarily submitted for advisory comment or submitted as 
1018  required under 21 CFR 314.550 or 601.45, if multiple promotional materials are included in one 
1019  submission, each of these materials is to be submitted with its own clean version, annotated 
1020  version, annotated labeling, and annotated references.   
1021   
1022  The following example shows how to submit multiple promotional materials in one submission 
1023  in section 1.15 for advisory comments: 
1024   
1.15 Promotional material (Professional) 
1.15.1 Correspondence relating to promotional materials 
1.15.1.1 Request for advisory comments on launch materials 
     Request for professional launch advisory for sales aid and print ad 20140501            
1.15.2 Materials (Request for Advisory Launch) 
1.15.2.1 Material (Sales Aid)(65NO35482) 
1.15.2.1.1 Clean version 
    Sales aid 65NO35482 Considerations for treatment 20140501 CLEAN 
1.15.2.1.2 Annotated version 
     Sales aid 65NO35482 Considerations for treatment 20140501 ANNOTATED 
1.15.2.1.3 Annotated labeling version 
     PI annotated to sales aid 
1.15.2.1.4 Annotated references  
     Reference 1 Smith et al. for sales aid 
1.15.2.1 Material (Print Ad)(77UY6788) 
1.15.2.1.1 Clean version 
     Print ad 77UY6788 A new option 20140501 CLEAN 
1.15.2.1.2 Annotated version 
     Print ad 77UY6788 A new option 20140501 ANNOTATED 
1.15.2.1.3 Annotated labeling version 
     PI annotated to print ad 
1.15.2.1.4 Annotated references  
     Reference 1 Murray et al. for print ad 
     Reference 2 Shoon et al. for print ad 
1025   
1026  For promotional materials submitted in fulfillment of the postmarketing reporting requirements, 
1027  if multiple promotional materials are included in one submission, submit clean versions of each 
1028  promotional material in section 1.15.2.1.1.   
1029   
  29  Contains Nonbinding Recommendations 
 
1030  The following example shows how to submit multiple promotional materials in one submission 
1031  in section 1.15: 
1032   
1.1 Forms 
  Form FDA 2253:  Transmittal of Advertisements and Promotional Labeling for Drugs  
  And Biologics for Human Use  
          Form FDA 2253 Professional website and print ad 20140105 
1.14 Labeling 
1.14.6 Product labeling for 2253 submissions 
    Drug X PI Rev20131205 
1.15 Promotional material (Professional) 
1.15.2 Materials (Promotional 2253) 
1.15.2.1 Material (www-website)(68443439)(20140105) 
1.15.2.1.1 Clean version 
     Website 68443439 Challenges to treatment 20140105 CLEAN 
1.15.2.1 Material (Print Ad)(3945730)(20140105) 
1.15.2.1.1 Clean version 
     Print ad 3945730 A new treatment 20140105 CLEAN 
1033   
1034  J.  Submission of Promotional Materials Referencing More Than One 
1035  Application (Grouped Submissions) 
1036   
1037  Firms are encouraged to submit promotional materials that promote more than one product (i.e., 
1038  a multiple-product submission) as a grouped submission.44  However, only one application type 
1039  can be used in a grouped submission.  Therefore, should a promotional material apply to more 
1040  than one application type (e.g., a BLA and NDA), submit the promotional material as a separate 
1041  submission for each application type (i.e., there would be two separate submissionsone for the 
1042  BLA application and one for the NDA application).    
1043   
1044  K.  Leaf Titles 
1045   
1046  Appropriately named leaf titles allow FDA reviewers to navigate through submissions and 
1047  distinguish one submission from another in the eCTD viewer.  A leaf title should include the MA 
1048  number if it has been provided in a previous communication with FDA. 
1049   
1050  The format of the leaf title for the actual form for Form FDA 2253 submissions (placed in 
1051  section 1.1) should be informative for Agency reviewers.  For example, the leaf title Form FDA 
1052  2253 Consumer print ad 20140105 is more informative and searchable than a leaf title of 
1053  2253Form.  Although both examples identify the submission by type, in the first example the 
1054  Agency reviewer will know the audience for the promotional material (consumer), the material 
1055  type code, and the date of the submissionall without having to open the file itself. 
1056   
 
44 For instructions on assembling grouped submissions, please see The eCTD Backbone Files Specification for 
Module 1, located in the eCTD Submission Standards on the FDA eCTD website at https://www.fda.gov/ectd. 
 
  30  Contains Nonbinding Recommendations 
 
1057  In addition, the leaf title for the correspondence related to promotional materials (placed in 
1058  section 1.15.1) should help the Agency reviewer identify the incoming submission by type.  A 
1059  leaf title of Response to untitled letter 20140105 MA37 is more informative than a leaf title of 
1060  Response to untitled letter, because the former example identifies the type of correspondence, 
1061  the letter date of the submission, and the MA number.   
1062   
1063  Leaf titles for each promotional material (placed in section 1.15.2) should also be informative.  
1064  For example, a health-care-professional-directed sales aid with the leaf title Sales Aid 
1065  65NO35482 Considerations for treatment 20140102 is more informative than the leaf title 
1066  promotional material.pdf.  When displayed in the eCTD viewer, the first example immediately 
1067  identifies the material type code, the material identifying number of the piece (if applicable), a 
1068  description of the piece, and the date of the submission.  All of this information is useful to the 
1069  Agency reviewer, even though there may be some redundancy between information in the leaf 
1070  title and the materials attributes discussed previously in section VI.F of this guidance.  
1071   
1072  L.  Use of Operator Attributes  
1073   
1074  When using life cycle operations, use the operator attributes as follows:  
1075   
1076    For resubmissions, use the replace operator attribute to replace the previously submitted 
1077  files with the resubmissions updated files.  If a firm is only resubmitting part of the original 
1078  submission, the operator for the correspondence file should be new. 
1079   
1080    For withdrawals, submit the withdrawal request and use the delete operator attribute on all 
1081  leaves that are affected by the withdrawal request.  The operator for the correspondence file 
1082  should be new. 
1083   
1084    For promotional materials submitted in fulfillment of the postmarketing reporting 
1085  requirements (2253 submissions), if a material previously submitted under cover of Form 
1086  FDA 2253 is revised, use the replace operator attribute to replace the previously submitted 
1087  files with the revised materials.  (The submission-sub-type should be Original, as indicated 
1088  in table 3 of this guidance.) 
1089   
1090   
1091  VII.  PRESENTATION ISSUES 
1092   
1093  Because electronic images may not adequately convey the net impression of the promotional 
1094  material or the details of the intended promotional message within the piece, firms should follow 
1095  the guidelines in this section to facilitate review by the Agency.    
1096   
1097  A.  General Presentation Considerations 
1098   
1099  In general, the presentation considerations below encompass the appearance, layout, format, and 
1100  visible impression of promotional materials submitted for all promotional submission types and 
1101  audiences.  Optimally, Agency reviewers should be able to use or view each promotional 
1102  material submitted to the Agency in the same manner as the end-user audience.  In instances 
  31  Contains Nonbinding Recommendations 
 
1103  when this is not possible, firms are to submit electronic promotional materials in a manner for 
1104  which the net impression is clear and legible; likewise for the individual representations in each 
1105  promotional material.   
1106   
1107  Provide each promotional material submitted to the Agency in electronic format as an individual 
1108  file in an approved file format.  If the current list of approved file formats does not allow the firm 
1109  to submit a fully functional piece, the submission must provide the ability to view all interactive 
1110  selection options as still images with annotations or notes that clearly describe the functionality 
1111  of the piece.  
1112   
1113  Please note that promotional materials submitted with Form FDA 2253 to OPDP must include a 
1114  representation of the actual piece that is disseminated rather than solely a proof or galley copy of 
1115  the promotional material.45  However, a proof or galley copy of the promotional material may 
1116  also accompany the actual piece as part of the submission in order to demonstrate layout or size 
1117  presentation elements.  Please refer to section VII.K of this guidance for additional details on 
1118  providing the size or dimensions of materials.  Proof or galley copies of the promotional material 
1119  should be submitted within section 1.15.2.1.2 of module 1.   
1120   
1121  B.  Visibility of Text and Images 
1122   
1123  Promotional materials should present clear and legible text and images regardless of the format 
1124  (electronic and/or physical media).  Although the Agency recognizes that electronic images and 
1125  text may require magnification on computer screens during the review process, the majority of 
1126  images and text within each electronic file should not require excessive magnification in order to 
1127  obtain the net impression of the piece or an understanding of the individual claims. 
1128   
1129  C.  Concise Description of Use 
1130   
1131  Each promotional material should include a concise description of use.  The description may 
1132  include, but should not be limited to, the purpose of the piece, setting of use for the piece, and/or 
1133  an explanation of additional materials that will be used in conjunction with the piece.  The 
1134  concise description of use may be presented on Form FDA 2253 under Comments, as a 
1135  comment on the electronic version of the promotional material, as a comment on an optional 
1136  proof or galley piece, and/or within the correspondence of a voluntary request for comments.  A 
1137  concise description of use is particularly important in situations where additional context is 
1138  necessary, such as the following: 
1139   
1140    The purpose of the promotional material is not self-evident after looking at an image of the 
1141  piece or reading its title (e.g., a journal ad may be designed with an appearance similar to a 
1142  booth panel). 
1143   
1144    The promotional material is designed for use only in conjunction with other specific 
1145  promotional materials.  
 
45 Proof or galley copies are samples or preliminary versions of promotional material created for review and/or 
proofreading by the firm.  
  32  Contains Nonbinding Recommendations 
 
1146   
1147    The promotional material is designed for use in a very specific setting.  
1148   
1149    The promotional material (with the same material ID number) is designed for multiple uses 
1150  in different and unique settings.  
1151   
1152  Concise descriptions of use may include, but should not be limited to, language such as: 
1153   
1154    Booth panel A will be used only in conjunction with booth panels B, C, and D. 
1155    For use as a journal ad and a physician leave-behind. 
1156    Item 1 of 5 of kit. 
1157    For one-time use during [Conference Title, Month/Year]. 
1158   
1159  D.  Layout Indicators 
1160   
1161  Firms should submit promotional materials with clear and legible indicators for navigating 
1162  through each promotional material, as applicable.  Indicators describing location and navigation 
1163  elements in the piece should be presented on each electronic page or image and should not 
1164  obstruct the image of the promotional materials.  Indicators may include, but should not be 
1165  limited to, the following: 
1166   
1167    Front cover, back cover, inside front cover, inside back cover 
1168    Bottom of piece or page, top of piece or page 
1169    Front of piece, back of piece 
1170    Page numbers  
1171    Inserts 
1172    Pockets and pocket content 
1173    Tabs or section dividers 
1174    Folds 
1175    Blank pages or panels 
1176    Annotations to references  
1177    Actual size 
1178    Clarifying the PI position 
1179   
1180  Indicators may be presented as symbols or text.  A key should be provided (e.g., along the 
1181  margin of the piece) if symbols are presented as indicators within a submission.  
1182   
1183  E.  Websites, Electronic Interactive Programs, and Electronic Detail Aids 
1184   
1185  Electronic promotional material submissions including, but not limited to, websites, electronic 
1186  interactive programs, and electronic detail aids should clearly display and communicate how the 
1187  promotional material will look and convey messages to the end user.  Preferably, the submission 
1188  should allow FDA reviewers to view and interact with the piece in the same manner as the end 
1189  user.  For example, static electronic images may not adequately convey how complex interactive 
1190  promotional materials convey promotional messages.  Such promotional submissions may also 
  33  Contains Nonbinding Recommendations 
 
1191  be accompanied by a video showing manipulation of the promotional program or application.  
1192  Also see the eCTD Technical Conformance Guide for additional considerations related to 
1193  submitting websites and other electronic promotional materials in the eCTD.46  
1194   
1195  In general, to comply with the postmarketing requirement for promotional materials in 21 CFR 
1196  314.81(b)(3)(i), a firm must submit its entire product website at the time of first use.  If the firm 
1197  then updates one page or section of the website, the firm need only submit the updated page or 
1198  section with a cross-reference to the original submission of the website noted on Form FDA 
1199  2253, including the date of the original submission.  If the website is substantially revised, the 
1200  firm must submit the revised website in its entirety.47,48 
1201   
1202  F.  Materials Requiring Physical Manipulation by the End User 
1203   
1204  Promotional materials requiring physical manipulation by the end user to obtain the net 
1205  impression of the promotional message (and/or the details of the promotional message) should be 
1206  submitted in a format that allows the Agency to view all aspects of the promotional material.  For 
1207  example, the electronic submission of a lenticular refrigerator magnet may display one image if 
1208  tilted left and an alternate image if tilted right.  Representations for both images should be 
1209  submitted in this case.    
1210   
1211  G.  Three-Dimensional Promotional Materials 
1212   
1213  Electronic submission of three-dimensional promotional objects should provide sufficient detail 
1214  to allow FDA to view the promotional material from all possible views.  In addition, images 
1215  should provide adequate information to allow Agency reviewers to determine the size of the 
1216  object (e.g., point size, dimensions).  In rare situations, it may not be possible to accurately 
1217  represent the promotional material in an electronic format.  In these situations, the best possible 
1218  electronic image should be submitted electronically, and a courtesy copy of the promotional 
1219  material can also be sent for the reviewer.  The courtesy copy of the promotional material should 
1220  be submitted as a general correspondence and should include a reference to the electronic 
1221  submission and sequence number. 
1222   
 
46 The eCTD Technical Conformance Guide is available on the FDA eCTD website at https://www.fda.gov/ectd. 
 
47 If submitted in eCTD format, an updated page or section of a website should be submitted with the submission-
sub-type of Original and the operator attribute new.  If a website is substantially revised, the submission-sub-
type should be Original and the replace operator attribute should be used to replace the previously submitted 
files with the revised website.  Please refer to section VI.L of this guidance for more information about the use of 
operator attributes. 
 
48 For more information regarding fulfilling regulatory requirements for postmarketing submissions of interactive 
promotional media, see the draft guidance Fulfilling Regulatory Requirements for Postmarketing Submissions of 
Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics.  When final, this guidance 
will represent FDAs current thinking on this topic. 
 
  34  Contains Nonbinding Recommendations 
 
1223  H.  Multi-Page Spreads49 
1224   
1225  Promotional materials that include text or images that span more than one page or for which the 
1226  promotional message may be interpreted as spanning more than one page (e.g., a two- or three-
1227  page brochure spread) should include a clear image or representation of the entire spread within 
1228  a single view.  All possible spreads of a given promotional material should be presented.  In 
1229  addition, electronic images of print materials and electronic materials should be presented in a 
1230  manner and sequence as they would appear to the end user. 
1231   
1232  I.  Kits 
1233   
1234  Electronic submission of kits should clearly indicate the components of the kit.  Components of 
1235  the kit that are not intended for distribution apart from the kit should be labeled as such.  The 
1236  accompanying Form FDA 2253 must include the material ID number or identifier for the kit, as 
1237  well as the material ID number or identifier for each individual component of the kit.   
1238   
1239  J.  Dimensions 
1240   
1241  All images of physical materials should include dimensions.  Acceptable methods to identify 
1242  dimensions include, but are not limited to, photographs of materials placed next to rulers, 
1243  annotations on PDF images, or prominent PDF bookmarks identifying the dimensions of a 
1244  piece.50  Images of three-dimensional pieces should be identified as such in the descriptions and 
1245  should provide information adequate to determine height, width, and depth dimensions.   
1246   
1247  Dimensions should be presented with standard units of measure. 
1248   
1249  K.  Examples of Appropriately Submitted Promotional Materials 
1250   
1251  Although not exhaustive, the following examples illustrate appropriate electronic submissions of 
1252  promotional materials in terms of presentation issues: 
1253   
1254  Example 1:  A firm creates a website for a new product that includes links and videos  As 
1255  part of its postmarketing requirements, the firm must submit an electronic version of the 
1256  product website under cover of Form FDA 2253.  The firm consults the eCTD Technical 
1257  Conformance Guide and the Specifications for File Format Types Using eCTD Specifications 
1258  for additional considerations regarding submitting websites in acceptable formats.51  The 
1259  submission should allow the FDA reviewer to click on links within the website and view 
 
49 In this guidance, the term spread is used to refer to adjacent pages of promotional material with related matter or 
connecting elements extending across the fold.  
 
50 For additional details regarding the submission of PDF documents in eCTD format, please see the Portable 
Document Format (PDF) Technical Specifications Document available at https://www.fda.gov/ectd.  
 
51 The eCTD Technical Conformance Guide is available on the FDA eCTD website at https://www.fda.gov/ectd. 
The Specifications for File Format Types Using eCTD Specifications is in the eCTD Submission Standards on the 
FDA eCTD website at https://www.fda.gov/ectd. 
  35  Contains Nonbinding Recommendations 
 
1260  videos or other animations as an end user will experience while using the site.52  If the firm is 
1261  unable to provide active links within the electronic submission, the firm should provide 
1262  electronic images of each web page in conjunction with videos.  
1263   
1264  Example 2:  A firm is disseminating an electronic version of a promotional labeling piece 
1265  containing a health-care-professional-directed quiz.  As part of its postmarketing 
1266  requirements, the firm should submit an electronic working version of the quiz under cover 
1267  of Form FDA 2253.  If the firm is unable to provide a working version of the quiz, the 
1268  submission must include images that convey the results of selecting correct answers as well 
1269  as the images resulting from incorrect answers.   
1270   
1271  Example 3:  A firm voluntarily submits, for comments, an electronic image of a promotional 
1272  mug that displays a product logo, a frequently used tagline, and a graphic that appears on the 
1273  mug when hot liquid is added.  The submission should include images of the front, back, 
1274  inside, bottom, and sides of the mug, regardless of whether any particular view contains a 
1275  promotional claim or representation.  In addition, the submission should also include images 
1276  of the mug when hot liquid is added, along with an explanation of when the images appear.  
1277  Such a submission would benefit from layout indicators such as front, back, and 
1278  intentionally left blank, in addition to measurement indicators. 
1279   
1280  Example 4:  A firm voluntarily submits, for comments, an electronic image of a trifold 
1281  branded print brochure.  The firm should present, in the following order, images of (1) the 
1282  front cover of the brochure, (2) all possible two-page spreads when the brochure is partially 
1283  opened, (3) the single three-page spread when the brochure is completely opened, and (4) the 
1284  back cover of the brochure.  Such a submission would benefit from layout indicators such as 
1285  front panel, rear panel, 2-panel spread, and 3-panel spread, in addition to 
1286  measurement indicators.     
1287   
1288  Example 5:  A firm is developing a kit that includes consumer-directed promotional materials 
1289  that are exclusive to the kit to be submitted for voluntary comments  For each piece of 
1290  material included in the kit, the firm should provide a concise description for use.  For 
1291  example, a promotional material that is intended only for distribution within the kit would 
1292  include the following description: Intended for distribution in consumer-directed sample kit 
1293  only. 
1294   
1295  Example 6:  A firm is developing a Form FDA 2253 submission for an electronic banner 
1296  used within an exhibit booth.  The firm should submit a working version of the banner.  
1297  However, if a working version of the banner cannot be submitted, the firm should submit a 
1298  video of the banner in conjunction with screen shots.  This is preferable to a submission 
1299  consisting only of static screen shots.  For example, the submission should include a video of 
1300  the banner along with screen shots that convey how the message will scroll, the time lapse 
1301  for the complete scroll of the message, and any variation in the rate that the message is 
1302  scrolled across a screen.   
1303   
 
52 A fully functional website should be submitted in an accessible format whenever possible.  Firms should not send 
links to websiteseven if they are password-protected.  
  36  Contains Nonbinding Recommendations 
 
1304  Example 7:  A firm is developing a Form FDA 2253 submission for a consumer-directed 
1305  branded video game that is embedded within a standard website.  If a working version of the 
1306  game cannot be submitted using an acceptable file format, the firm should submit a video of 
1307  the game being played in addition to electronic still images of the game.  If the game will 
1308  also be available to consumers within a conference exhibit setting, the firm should include a 
1309  concise description of use disclosing this additional unique setting. 
1310   
1311  VIII.  PAPERWORK REDUCTION ACT OF 1995  
1312   
1313  This guidance contains information collection provisions that are subject to review by the Office 
1314  of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
1315  (44 U.S.C. 3501-3520).   
1316   
1317  The time required to complete this information collection is estimated to average the following: 
1318   
1319    51 hours for promotional labeling voluntarily submitted for comments, including 
1320  resubmissions and amendments  
1321    3 hours for general correspondence submitted to FDA 
1322    3 hours for requests to withdraw a previous submission to FDA 
1323    13 hours for responses to untitled or warning letters 
1324    13 hours for responses to information requests 
1325    13 hours for reference documents 
1326    13 hours for complaints submitted to OPDP 
1327   
1328  These estimates include the time to review instructions, search existing data sources, gather the 
1329  data needed, and complete and review the information collection.  Send comments regarding this 
1330  burden estimate or suggestions for reducing this burden to:   
1331     
1332  Office of Prescription Drug Promotion, Center for Drug Evaluation and Research, Food 
1333  and Drug Administration, 10903 New Hampshire Avenue, Bldg. 51, Rm. 3374, Silver 
1334  Spring, MD 20993-0002 
1335   
1336  This guidance also refers to previously approved collections of information found in FDA 
1337  regulations and collections of information that are currently under OMB review.  The collections 
1338  of information in 21 CFR 202.1, including voluntary requests for advisory comments, 
1339  resubmissions, and amendments for advertisements, have been approved under OMB control 
1340  number 0910-0686; the collections of information in 21 CFR 601.45 (presubmission of 
1341  promotional materials for accelerated approval products under part 601) have been approved 
1342  under OMB control number 0910-0338; the collections of information for Form FDA 2253 and 
1343  the presubmission of promotional materials for accelerated approval products under 21 CFR part 
1344  314 have been approved under OMB control number 0910-0001.   
1345     
1346  An Agency may not conduct or sponsor, and a person is not required to respond to, a collection 
1347  of information unless it displays a currently valid OMB control number.  The OMB control 
1348  number for this information collection is 0910-0001.  To find the current expiration date, search 
1349  for this OMB control number at https://www.reginfo.gov.    
  37