Providing Regulatory Submissions in Electronic and Non-Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs

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

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Providing Regulatory Submissions in Electronic and Non-Electronic Format — Promotional Labeling and Advertising Materials for Human Prescription Drugs

Guidance for Industry

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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

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

F. Materials (Section 1.15.2) 26

Attributes 26
Clean Version of Materials Submitted (Section 1.15.2.1.1) 27
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
Product Labeling Accompanying Form FDA 2253 Submissions (Section 1.14.6) 28
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

Contains Nonbinding Recommendations

Providing Regulatory Submissions in Electronic and Non-Electronic Format — Promotional Labeling and Advertising Materials for Human Prescription Drugs

Guidance for Industry

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page.

I. INTRODUCTION

This guidance pertains to submissions of promotional materials for human prescription drugs (drugs) to the Food and Drug Administration (FDA or Agency) made by manufacturers, packers, and distributors (firms), whether the applicant or an entity acting on behalf of the applicant. Specifically, this guidance pertains to submissions made to the Office of Prescription Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) and the Advertising and Promotional Labeling Branch (APLB) in the Center for Biologics Evaluation and Research (CBER). This guidance also explains certain aspects of electronic submission of

https://www.regulations.gov/docket/FDA-2015-D-1163

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https://www.fda.gov/RegulatoryInformation/Guidances/default.htm

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Contains Nonbinding Recommendations

promotional materials in module of the electronic common technical document (eCTD), using version 3.3 or higher of the us-regional-backbone file.

For the purpose of this guidance, the term promotional materials collectively refers to promotional labeling and advertising materials, regardless of the format, manner, or medium by which they are presented. Promotional materials may include, but are not limited to, television advertisements (ads), brochures, booklets, detailing pieces, internet websites, print ads, exhibits, sound recordings, and radio ads.

The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.

An exception to that framework derives from section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), wherein Congress granted authorization to FDA to require that 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 specified by FDA through guidance. Accordingly, insofar as this guidance requires that submissions under section 505(b), (i), or (j) of the FD&C Act and submissions under section 47 351(a) or (k) of the PHS Act be submitted in electronic format specified by FDA, this document is not subject to the usual restriction in FDA’s good guidance practice regulations that guidances not establish legally enforceable responsibilities. Therefore, the portion of this guidance that establishes the requirement for electronic submissions under section 745A(a) of the FD&C Act has binding effect, as indicated by the use of the words must, shall, or required.

II. BACKGROUND

A. Electronic Submissions to FDA Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act

Section 745A(a) of the FD&C Act, added by section 1136 of the Food and Drug Administration Safety and Innovation Act (FDASIA) (Public Law 112-144), requires that submissions under section 505(b), (i), or (j) of the FD&C Act and submissions under section 351(a) or (k) of the PHS Act be submitted in electronic format specified by FDA beginning no earlier than months after FDA issues a guidance specifying such electronic submission format. Certain types of promotional-material-related submissions discussed in this guidance are “submissions under subsection (b), (i), or (j) of section 505 of this Act or subsection (a) or (k) of section 351 of the Public Health Service Act” and are, therefore, subject to the requirements of section 745A(a). Specifically, this includes the following:

Contains Nonbinding Recommendations

* Postmarketing submissions of promotional materials using Form FDA 2253 (required by 21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4))

* 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 where such submissions are required for approval under section 505(b), (i), or (j) of the FD&C Act

The guidance for industry Providing Regulatory Submissions in Electronic Format — Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (December 2014) (the 745A(a) Implementation Guidance) sets forth general information on how FDA interprets and intends to implement the electronic submission requirements of section 745A(a) of the FD&C Act. The 745A(a) Implementation Guidance states that it is not feasible to describe and implement the electronic format(s) that would apply to all the submissions covered by section 745A(a) in one guidance document. Instead, FDA will periodically issue guidances specifying the electronic format for certain types of submissions. The guidance for industry Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (April 2018) (the eCTD Guidance) specifies the general format for certain types of electronic submissions using the eCTD, including the specifications for module 1.

In addition to the more general information and implementation timeline found in those guidances, this guidance provides additional information regarding the format to use for electronic submission of promotional labeling and advertising materials, using the eCTD. Accordingly, months after the issuance of this guidance, firms will be required to submit electronically all promotional submissions that fall within the scope of section 745A(a) as specified in this guidance. As of that date, paper copies will no longer be accepted for such submissions. Note that although only the promotional submissions discussed in sections IV.A and IV.B that fall within the scope of section 745A(a) will be required to be submitted electronically in the format specified in this guidance, firms may voluntarily choose to submit electronically other types of promotional material submissions discussed in this guidance.

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Contains Nonbinding Recommendations

This document also discusses types of promotional materials that are not subject to the mandatory electronic submission requirement in section 745A, (i.e., all promotional materials discussed in this document other than postmarketing submissions of promotional materials using Form FDA 2253 and submissions of promotional materials for accelerated approval products, as discussed in sections IV.C through K of this guidance).

B. Promotional Labeling and Advertising

Section 201(m) of the FD&C Act defines labeling as “all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article” (21 U.S.C. 321(m)). The U.S. Supreme Court has explained that the language “accompanying such article” in the labeling definition is interpreted broadly to include materials that supplement or explain an article. No physical attachment between the materials and the article is necessary; rather, it is the textual relationship between the items that is significant (Kordel v. United States, 335 U.S. 345, 350 (1948)).

FDA generally recognizes two types of labeling for drugs: (1) FDA-required labeling and (2) promotional labeling. FDA-required labeling is labeling that is necessary to fulfill the minimum requirements of the FD&C Act and its implementing regulations. For prescription drugs, the required labeling is the labeling, drafted by the manufacturer, that is reviewed and approved by FDA as part of a new drug application (NDA), an abbreviated new drug application (ANDA), or a biologics license application (BLA) (21 CFR 314.50(c)(2), 314.94(a)(8), and 601.2(a)). Promotional labeling is generally any labeling, other than the FDA-required labeling, that is devised for promotion of the product. Examples of materials that may be considered promotional labeling pieces for prescription drugs are described in 21 CFR 202.1(l)(2).

The FD&C Act does not define what constitutes an advertisement, but FDA regulations provide several examples including, but not limited to, materials “in published journals, magazines, other periodicals, and newspapers and in advertisements broadcast through media such as radio, television, and telephone communication systems” (21 CFR 202.1(l)(1)).

III. GENERAL CONSIDERATIONS

All submissions of promotional materials should meet a set of criteria in order to be reviewed by the Agency. Firms should ensure that the following information is provided and considerations are met when submitting promotional materials, regardless of the format in which the materials are submitted:

* Include the appropriate NDA, ANDA, or BLA number.

* For OPDP, address submissions that require correspondences to the attention of the OPDP Project Manager.

* Use the most specific material type (from Form FDA 2253) to describe the promotional material that is the subject of the submission (e.g., do not use the code “promotional labeling” when another code is available that gives a more specific description of the promotional material).

* Submit different types of promotional material submissions separately (e.g., do not submit materials on Form FDA 2253 per the requirement in 21 CFR 314.81(b)(3)(i)) together with a voluntary request for advisory comments on launch materials).

* Submit promotional materials separately from other types of submissions (i.e., submissions not related to promotional materials).

* Submit promotional materials directed to health care professionals separately from submissions of promotional materials directed to consumers.

Occasionally, promotional materials may be directed to both consumers and health care professionals. In those circumstances, firms should identify the audience type based on the end- user for the bulk of the information. For example, press releases should be submitted as consumer-directed materials unless they are specifically intended for health care professionals. Websites with distinct sections for health care professionals and consumers should be divided into two separate submissions. If the website does not have distinct sections for each audience and is not intended to be directed solely to health care professionals, firms should submit the entire website as a consumer submission.

In cases where a company that holds the application collaborates with another firm to promote the drug (e.g., a collaborative marketing agreement where another firm that is not the application holder disseminates and submits promotional materials based on a contractual agreement with the application holder), the application holder should send a general correspondence submission to OPDP or APLB describing the agreement. In addition, the business relationship should be indicated in subsequent submissions of promotional materials.

IV. CONTENT FOR SPECIFIC TYPES OF SUBMISSIONS

The content of various types of submissions to the Agency relating to promotional materials is described below and applies to submissions in both eCTD and non-eCTD format. Also, as described in section II of this guidance, submissions described below under sections IV.A and IV.B must be submitted electronically per the requirements in section 745A(a) of the FD&C Act.

Contains Nonbinding Recommendations

The advertising and promotional labeling submissions described below represent the types of submissions that FDA currently receives.

A. Promotional Materials Submitted in Fulfillment of the Postmarketing Reporting Requirements (Form FDA 2253 Submissions)

Under the FD&C Act and FDA's regulations implementing postmarketing reporting requirements, applicants must submit specimens of mailing pieces and any other labeling or advertising devised for promotion of the drug product at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product (21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4)). Each submission (also referred to as a 2253 submission) is required to be accompanied by a completed fillable Form FDA 2253 (Transmittal of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use) and is required to include a copy of the product’s current professional labeling (21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4)).

The following provides details on submitting promotional materials in fulfillment of postmarketing reporting requirements. OPDP and APLB have different procedures, so firms should pay careful attention to the following information.

Firms are required to include the following:

* Form FDA 2253: Transmittal of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use. (For OPDP submissions, submit this form with final promotional materials only.) Firms must use the most current version of the fillable Form FDA 2253.12,13

On Form FDA 2253, box titled “For CBER Products Only”:

o OPDP: Do NOT check the “Draft” or “Final” boxes.

o APLB: Check the “Final” box only for Final postmarketing submissions.

For cases where promotional materials mention multiple products, note the lead application number on Form FDA 2253 and include an attachment that identifies the other referenced products (e.g., application type and number, trade name, established name).

* Promotional material(s).

* Current product labeling.

https://www.fda.gov/about-fda/reports-manuals-forms/forms

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Firms are also encouraged, but not required, to submit annotated versions of the promotional material(s) cross-referenced to the product labeling and references, if applicable.

Professional and consumer materials should be submitted separately and should not include a cover letter or correspondence. For 2253 submissions to OPDP, if a drug has multiple approved indications that are covered by different reviewers in OPDP, firms should submit (when possible) promotional materials that only promote one indication separately from promotional materials that promote only another indication. In such cases, firms may choose to communicate the indication being promoted in the promotional materials in the Comments section of Form FDA 2253.

B. Presubmission of Promotional Materials for Accelerated Approval Products

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 with other products where such submissions are required for approval must submit promotional 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 accelerated approval of a drug product on the condition, among others, that the sponsor submit copies of all promotional materials related to the product during the preapproval review period and, following approval and for such period thereafter as the Agency determines to be appropriate, at least 30 days before dissemination of the materials. Additionally, there may be other situations when the Secretary of Health and Human Services may establish presubmission conditions on promotional materials similar to those in place for accelerated approval products (e.g., section 564(e)(4)(A) of the FD&C Act). In such situations, like the drug products approved under the accelerated approval framework, sponsors will be required to use the format for electronic submission outlined in section VI of this guidance, no earlier than 24 months after publication of this guidance.

According to 21 CFR 314.550 and 21 CFR 601.45, unless otherwise informed by the Agency, applicants being considered for accelerated approval must submit to the Agency, during the preapproval review period, copies of all promotional materials, including both promotional labeling and ads, intended for dissemination or publication within 120 days following marketing approval (launch). Under the same regulatory provisions, after 120 days following marketing approval, unless otherwise informed by the Agency, the applicant must submit promotional materials at least 30 days before the intended time of initial dissemination of the labeling or initial publication of the advertisement (non-launch).

Contains Nonbinding Recommendations

The submission should include the following:

* Correspondence stating that it is a presubmission of promotional material(s) for an accelerated approval product (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

* A clean version of the draft promotional material(s) that does not include annotations to the label or references

* An annotated copy of the proposed promotional material that clearly identifies the source of support for each claim (e.g., specific page and lines of the FDA-approved full prescribing information (PI) or specific page and column/paragraph from other references)

* The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the proposed promotional material

* If applicable, annotated references to support product claims not contained in the PI, cross- referenced to the proposed promotional material

* If applicable, annotated references to support disease or epidemiology information, cross- referenced to the proposed promotional material

For draft promotional materials submitted to APLB under 21 CFR 601.45, use Form FDA 2253 with box titled “For CBER Products Only” checked as “Draft.” Do not use Form FDA 2253 for submissions of draft promotional materials for accelerated approval products to OPDP under 21 CFR 314.550 or 21 CFR 601.45.

C. Promotional Materials Submitted Voluntarily for Advisory Comments

Section 21 CFR 202.1(j)(4) provides firms with a voluntary opportunity to submit promotional materials to FDA for advisory comment before the dissemination or publication of those promotional materials. Firms may request advisory comments on draft promotional materials and receive comments in writing from the Agency. Because this process is intended to provide input before dissemination or publication, if the Agency learns that the materials submitted or that substantially similar claims or presentations have been disseminated or published— including after submission for comments—the Agency will generally not review the materials under the voluntary advisory comment process.

1. Requests for Comments on Draft Promotional Materials Other Than DTC TV Ads Under 21 CFR 202.1(j)(4)

Launch materials are draft promotional materials that are voluntarily submitted by a firm to OPDP or APLB during the launch phase (i.e., the first 120 days that an FDA-approved product, indication, delivery system, formulation, dosage form, dosing regimen, strength, or route of administration is marketed to the public) for review and comment before dissemination or publication.

Contains Nonbinding Recommendations

Requesting comments on promotional materials before launch is encouraged. Review of core launch materials is a high priority for Agency reviewers. Core launch materials generally include the following:

* One comprehensive promotional labeling piece directed toward professionals (e.g., sales aid, visual aid, detail aid, or exhibit panel (if there is a major conference within the launch phase)), limited to 12 or fewer pages

* One advertisement directed toward professionals (e.g., journal ad), limited to 4 or fewer pages, not including the PI or brief summary

* One comprehensive direct-to-consumer (DTC) labeling piece (e.g., patient brochure), limited to 12 or fewer pages

* One DTC advertisement (e.g., magazine ad), limited to 4 or fewer pages, not including the brief summary

* A professional and/or DTC product website (limited to 12 printed legible pages each) or electronic sales aid if it is a derivative (i.e., contains similar claims and/or presentations) of a comprehensive labeling piece that is also submitted for voluntary advisory comment

Launch materials other than those listed above (e.g., slide kits and materials longer than the page limits listed above) are considered non-core launch materials. Non-core launch materials are a lower priority than core launch materials. The Agency recommends that firms apply the Agency’s comments on the core materials to non-core materials.

Non-launch materials consist of draft promotional materials that a firm voluntarily submits to OPDP or APLB for review and comment before their first use in the public domain but after the launch phase (i.e., after the first 120 days that an FDA-approved product, indication, delivery system, formulation, dosage form, dosing regimen, strength, or route of administration is marketed to the public).

In general, the submission should include the following:

* Correspondence stating that it is a voluntary request for advisory comments (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

* A clean version of the draft promotional material(s) that does not include annotations to the label or references

* An annotated copy of the proposed promotional material(s) that clearly identifies the source of support for each claim (e.g., specific page and lines of the PI or specific page and column/paragraph from other references)

* The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the proposed promotional material

* If applicable, annotated references to support product claims not contained in the PI, cross- referenced to the promotional material

* If applicable, annotated references to support disease or epidemiology information, cross- referenced to the promotional material

The following are recommendations for voluntarily submitting draft promotional materials— other than TV ads—for advisory comments:

* Draft promotional materials submitted for comment should be consolidated together into one submission for each intended audience (i.e., one submission with professional materials and one submission with consumer materials).

* It is also suggested that draft core launch materials be consolidated into a single submission for each intended audience rather than sending the materials piecemeal in several submissions over the course of a few days or weeks.

* In cases when the firm intends to submit professional and consumer launch core materials at around the same time, it is suggested that both submissions be sent on the same day.

* Likewise, it is suggested that draft non-core launch promotional materials be consolidated into single submissions for each intended audience to the extent possible.

* Submissions of draft DTC TV ads should not be included in submissions with other types of materials. (See section VI of this guidance for information on how to submit.)

Requests for Comments on Proposed DTC TV Ads Under 21 CFR 202.1(j)(4)

The submission should include the following:

* Correspondence stating it is a voluntary request for advisory comments on a proposed TV ad (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

Contains Nonbinding Recommendations

• A clean version of the storyboard of the proposed TV ad that does not include annotations to the label or references

• An annotated version of the storyboard of the proposed TV ad that clearly identifies the source of support for each claim (e.g., specific page and lines of the PI or specific page and column/paragraph from other references)

• The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the storyboard

• Other appropriate documentation if any of the following apply:

Annotated references to support product claims not contained in the PI, cross-referenced to the storyboard
If the advertisement identifies a person as an actual patient (e.g., a spokesperson) or actual health care professional, a signed statement by that person verifying that he or she has in fact used or prescribed the drug product for the advertised indication and is not merely an actor or model
Verification, in the form of a signed statement by the translator, that an official translation of a foreign-language TV ad is accurate
Annotated references to support disease or epidemiology information, cross-referenced to the storyboard
Optionally, submissions for advisory review may include a video or animatic of the proposed TV ad (if included, the video or animatic should be in an acceptable file format)

Materials unrelated to a proposed TV ad being voluntarily submitted for advisory comment should not be included in the review package. However, more than one TV ad proposal for a particular indication for a product may be submitted in the same submission.

D. Resubmissions

After FDA has responded to a voluntary request for advisory comments or has commented on an accelerated approval presubmission, firms may revise and resubmit draft materials.

In general, the resubmission should include the following:

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Contains Nonbinding Recommendations

* Correspondence stating that it is a voluntary request for advisory comments on a revised submission (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

* A clean version of the draft promotional material(s) that does not include annotations to the label or references

* An annotated copy of the proposed promotional material that clearly identifies the source of support for each claim (e.g., specific page and lines of the PI or specific page and column/paragraph from other references)

* The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the proposed promotional material

* If applicable, annotated references to support disease or epidemiology information, cross- referenced to the proposed promotional material

* If applicable, annotated references to support product claims not contained in the PI, cross- referenced to the proposed promotional material

E. General Correspondence

General correspondence includes any correspondence submitted to FDA that may or may not reference a specific drug product application and that does not fall into one of the other categories (e.g., 2253 submission, voluntary request for advisory comments). Please note that complaints should not be submitted under the category of "general correspondence."

Examples of types of correspondence to submit under this category include the following:

* Letters in which a firm informs OPDP or APLB of an error that occurred in its promotional material(s) or activities for its drug product(s)

* Safety update letters in which a firm informs OPDP or APLB that it will promptly revise all of its promotional materials for a particular drug(s), to be consistent with new safety information added to the product labeling

* General responses to comments from FDA provided in response to advice (voluntary request for comments or general) when no revised materials are included and there is no further

Contains Nonbinding Recommendations

voluntary request from the firm to FDA for advisory comments (include the Marketing & Advertising (MA) number)

* Notifications from a firm to FDA that it plans to disseminate or publish promotional materials for accelerated approval products previously submitted as required under CFR 473 314.550 or 601.45 before receipt of comments by FDA (e.g., after 30 days for a non-launch presubmission or after application approval for a launch submission)

* Notifications from a firm regarding agreements with other companies for the promotion of the product

* Notifications from a firm regarding a change in promotional labeling and advertising contact information

The submission should include the following:

* Correspondence stating that it is a general correspondence (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

F. Amendments (Submission of Previously Missing or Rejected Materials)

If a previous voluntary request for advisory comments, a presubmission for accelerated approval product, or a 2253 submission to FDA is missing one or more of the promotional materials listed in the correspondence or on Form FDA 2253, these materials should be submitted as amendments. Amendments may also be submitted if an incorrect document file was included with a submission in eCTD format.

For voluntary requests for advisory comments, the submission should include the following:

* Correspondence stating that it is an amendment that includes accompanying materials that were previously missing (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

* Promotional material(s) or the correct document that was omitted from a previous submission to FDA

* Annotated copy of the promotional materials that were omitted from a previous submission to FDA

* The most current FDA-approved PI and, if applicable, the FDA-approved patient labeling or Medication Guide with annotations cross-referenced to the proposed promotional material

* If applicable, annotated references to support disease or epidemiology information, cross- referenced to the proposed promotional material that was previously omitted from a submission to FDA

* If applicable, annotated references to support product claims not contained in the PI, cross- referenced to the proposed promotional material that was previously omitted from a submission to FDA

If an incorrect document was included or if FDA notifies a firm that promotional materials are missing from a previous 2253 submission that was submitted in paper or non-eCTD format, the firm should resubmit the entire 2253 submission rather than submitting an amendment. If part of a non-eCTD 2253 submission is rejected (e.g., a video does not play), the entire 2253 submission should be resubmitted.

If the 2253 submission was in eCTD format, the firm should submit an amendment and include the following:

* Correspondence stating that it is an amendment that includes accompanying promotional materials that were previously missing or rejected (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

* Promotional materials that were missing or rejected from a previous submission to FDA (firm does not need to resubmit the entire 2253 submission)

Example: A firm voluntarily submits a request for advisory comments on launch promotional materials, using the eCTD. The correspondence file states that three promotional materials are included in the submission along with annotated copies and references. However, upon receipt, FDA notes that the actual submission only includes two promotional materials with annotated copies and references. FDA notifies the firm that one promotional material is missing from the submission and provides the MA number. The firm should then submit the missing promotional material and the annotated copy and references as an amendment, using the eCTD. The subject line of the correspondence should note that the submission is an amendment and include the MA number.

G. Withdrawal Requests

A firm may request to withdraw a previous submission to FDA. No materials are submitted with such a request.

Contains Nonbinding Recommendations

Because submission of promotional materials for accelerated approval products is required under 21 CFR 314.550 and 601.45, firms should only use a withdrawal request for such materials if the firm does not plan to disseminate or publish the promotional materials.

The submission should include the following:

• Correspondence stating that it is a withdrawal request (Please refer to section VI.E of this guidance for additional details about what to include in the correspondence.)

Example 1: A firm voluntarily submits draft promotional materials for advisory review for its product (not approved under the accelerated approval regulations at 21 CFR 314.510 or 601.41) and later decides to disseminate the promotional materials without waiting for FDA comments. The firm should notify FDA of its intent to withdraw the request for comments. The subject line of the correspondence should note that the submission is a withdrawal request and include the date of the request or MA number.

Example 2: A firm voluntarily submits draft promotional materials for advisory review for its product (not approved under the accelerated approval regulations at 21 CFR 314.510 or 601.41) and later decides not to disseminate the promotional material. The firm should notify FDA of its intent to withdraw the request for comments. The subject line of the correspondence should note that the submission is a withdrawal request and include the date of the request or MA number.

Example 3: A firm submits draft non-launch promotional materials for its product approved under the accelerated approval regulations at 21 CFR 314.510 or 601.41 and, two weeks later, decides that it does not intend to disseminate the promotional material. The firm should notify FDA of its intent to withdraw the submission. The subject line of the correspondence should note that the submission is a withdrawal request and include the date of the submission or MA number.

Example 4: A firm submits final promotional material under cover of Form FDA 2253 in fulfillment of the postmarketing reporting requirements and subsequently decides that it will never disseminate the promotional material. The firm should immediately notify FDA of its intent to withdraw the 2253 submission by submitting a correspondence. The subject line of the correspondence should note that the submission is a withdrawal request and include the date of the submission or MA number. Please refer to section VI.E of this guidance for additional details about what to include in the correspondence.

H. Response to Untitled Letter or Warning Letter

A response to an untitled letter or a warning letter is a correspondence type that includes a firm’s initial response or additional correspondence pertaining to an untitled letter or warning letter from FDA regarding promotion.

The submission should include the following:

• Correspondence stating that it is a response to an untitled letter or warning letter — This response may include the firm’s initial or subsequent responses. (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

• Corrective piece(s), if applicable

I. Response to Information Request

FDA may issue a letter of inquiry to firms when investigating potentially violative activity. The firm’s response to a letter of inquiry is considered a response to an information request. FDA will notify the firm when a response should be considered a response to an information request. The correspondence should state that it is a response to an information request. The correspondence should include the firm’s response to the questions and issues raised in FDA’s letter of inquiry, including any materials FDA has requested. (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

J. Reference Document

Reference documents are annotated materials that were missing from a previous submission to FDA. Promotional materials that were entirely omitted from a previous submission should not be included in this type of submission. (Please refer to section IV.G of this guidance if promotional materials were entirely omitted from a previous submission.)

The submission should include the following:

• Correspondence stating that it is a reference document submission and the specific information regarding what is in the submission (i.e., annotated references, annotated promotional materials, and/or annotated labeling) — (Please refer to section VI.E of this guidance for additional details on what to include in the correspondence.)

• Annotated references, annotated promotional materials, and/or annotated labeling

Example: A firm voluntarily submits a request for advisory comments for non-launch materials that includes two clean copies of promotional materials. However, the submission does not include annotated copies of the promotional materials or annotated references. FDA notifies the firm and provides the MA number. The firm should submit the missing materials as a reference document. The subject line of the correspondence should note that it is a reference document submission and include the MA number.

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K. Complaints

Please note that complaints about prescription drug promotion are not accepted in eCTD format and should be submitted as either paper copies or in an electronic non-eCTD format. Please submit complaints regarding professional and consumer materials separately. A duplicate copy of the submission should be provided. Please do not include Form FDA 2253 or Form FDA 356h.

The submission should include the following:

* Correspondence stating that it is a complaint — Please include the drug, manufacturer, and specific regulatory concerns in the correspondence. In addition, the correspondence should include the name, title, address, phone, fax, and email of the person that the Agency should contact about issues related to the submission.

* Supporting information or documentation, if available.

V. FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS IN PAPER COPY

Paper copies of all promotional submission types will be accepted until 24 months following publication of this guidance. When paper copy materials are submitted, sponsors are encouraged, but not required, to include one non-eCTD copy of the contents of the submission on a CD and include a statement in the cover letter verifying that the contents of the CD match the contents of the paper submission. Please refer to tables 1 and 2 to determine the number of copies to submit for each submission type. Beginning 24 months after this guidance publishes, 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 materials for accelerated approval or other products where such submissions are required for approval under section 745A(a) of the FD&C Act (see table 1). (See section VI of this guidance for further discussion.)

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Please note that complaints are not accepted in the eCTD and should only be submitted as paper

copies. If any submission is submitted electronically in eCTD format, paper copies should not

also be submitted, unless specifically requested.

Table 1: Number of Paper Copies for Various Submission Types Based on Recipient

Type of Submission	Number of Paper Copies<br/>If Recipient is OPDP	Number of Paper Copies<br/>If Recipient is APLB
Voluntary advisory submission (not a TV ad)	3	2
Voluntary advisory submission of a TV ad	10*	2*
Presubmission of promotional materials for accelerated approval products	3	2
503C TV ad	12*	2*
Resubmission	3	2
General correspondence	2	2
Amendment	3	2
Withdrawal request
Response to notice of violation or warning letter	2	2
Response to information request	2	2
Reference document	3	2
Complaint	2	2

* If a video is provided, only one copy of the video is necessary.

Table 2: Number of Paper Copies of Promotional Materials to Submit in Fulfillment of the Postmarketing Reporting Requirements (2253 Submissions)*

2253 Submissions	Number of Paper Copies
If the promotional material(s) mentions a single product	2
If the promotional material(s) mentions multiple products	3

* The number of copies is the same for OPDP and APLB. Note that beginning 24 months after publication of this guidance, under section 745A(a) of the FD&C Act, firms will no longer be able to submit these promotional materials in paper copy.

OPDP and APLB will continue to accept promotional materials submitted in fulfillment of the postmarketing reporting requirements (2253 submissions) in electronic, non-eCTD, format (e.g.,

CDs) until 24 months after publication of this guidance. Such submissions do not require inclusion of a paper copy of the entire submission, except that a signed paper copy of Form FDA 2253 must be included to allow for processing. Please follow the recommendations in table 2 for the number of copies to submit.

A. Submitting Paper Copy Promotional Materials to OPDP

Please send paper copies to the following address:

Office of Prescription Drug Promotion Food and Drug Administration 5901-B Ammendale Road Beltsville, MD 20705-1266

For time-sensitive materials, please confirm receipt of the submission with a phone call to the OPDP project manager at 301-796-1200 or by email at

CDER-OPDP-RPM@fda.hhs.gov

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OPDP suggests applying an "OPDP" sticker or other prominent directional notation to the exterior of packages submitted to OPDP to help avoid misdirection of promotional materials. If it is not possible to add this notation to the exterior of the package, OPDP recommends adding a prominent directional notation (e.g., sticker, rubber stamp) to the cover letter itself.

B. Submitting Paper Copy Promotional Materials to APLB

Please send paper copies to the following address:

Advertising and Promotional Labeling Branch, HFM-602 Food and Drug Administration Center for Biologics Evaluation and Research Document Control Center 10903 New Hampshire Ave. WO71 – G112 Silver Spring, MD 20993-0002

Any questions for APLB may also be addressed to APLB by phone at 240-402-9158.

Contains Nonbinding Recommendations

VI. FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS ELECTRONICALLY

This section provides information on specific aspects of how to submit promotional labeling and advertising materials to FDA electronically in eCTD format. As discussed in section II of this guidance, there are two types of submissions related to promotional materials that are "submissions under subsection (b), (i), or (j) of section 505 of [the FD&C] Act or subsection (a) or (k) of section 351 of the Public Health Service Act" and are, therefore, subject to the mandatory electronic submission requirement in section 745A(a) of the FD&C Act.

The two types of submissions are as follows:

Postmarketing submissions of promotional materials using Form FDA 2253 (required by 21 CFR 314.81(b)(3)(i) and 21 CFR 601.12(f)(4))
Submissions of promotional materials for accelerated approval products (required by section 506(c)(2)(B) of the FD&C Act, 21 CFR 314.550, or 21 CFR 601.45) and other products where such submissions are required for approval

This guidance, along with the eCTD Guidance, specifies the electronic format for these submission types. Therefore, beginning no earlier than 24 months after publication of this guidance, firms will be required to submit these types of submissions electronically. As of that date, paper copies will no longer be accepted for such submissions.

Although the other types of submissions related to promotional materials discussed in this guidance are not subject to the mandatory electronic submission requirement in section 745A(a) of the FD&C Act, firms may—and are strongly encouraged to—make such submissions electronically. However, paper copies will still be accepted for submission types that do not fall under section 745A(a). We note that if firms do choose voluntarily to submit other materials electronically, CDER is currently only able to accept them in eCTD format using us-regional-v3-3.dtd. 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.

https://www.fda.gov/ectd

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In some cases, the company that holds the application for a drug collaborates with another company to promote the drug. If the company handling promotion of the drug wants to submit promotional materials to OPDP or APLB using the eCTD, the company should work with the application holder to ensure that both companies are using the same version of the us-regional- backbone file. If the submission is for OPDP, both companies will need to use the same version (for example, us-regional-v3-3.dtd). In addition, both companies should work together to come up with a system for generating sequence numbers in order to avoid the use of duplicate sequence numbers that will result in a rejection of one of the submissions. For example, a company could choose to assign a block of numbers to a particular vendor (e.g., start promotional submissions with sequence 5000).

Please note that the eCTD format accommodates a wide range of applications and related submission types other than submissions of promotional materials. Therefore, a specific submission may not use all of the possible section-heading elements in each module. The following sections describe specific procedures for submitting promotional labeling and advertising to FDA in eCTD format, including submissions made under section 745A(a) of the FD&C Act.

A. Submission-Description Element

The submission-description element is an optional field. FDA recommends including the submission-description element to provide a high-level description of the purpose of the submission and to help differentiate similar types of submissions. If used, the submission- description element should include the description of the type of submission and materials, the date of the submission, and the MA number (if the MA number has been provided in a previous communication with FDA).

The following are examples of helpful submission descriptions:

* Request for comments on professional launch website, print ad, and sales aid 20140501

* Withdrawal request 20140405 for print ad MA61 submitted on 20140115

* Response to untitled letter 20140301 MA456

* Reference documents for professional launch print ad 20140302 MA31

* Consumer 2253 submission 20140915

B. Submission-Type and Submission-Sub-Type

For all promotional materials submitted to FDA via the eCTD (including promotional materials submitted in fulfillment of the postmarketing reporting requirements), use the submission-type "Promotional Labeling Advertising." If promotional materials are submitted in the eCTD without specifying "Promotional Labeling Advertising" as the submission-type, the submission may not be appropriately routed to OPDP or APLB and, as a result, there may be a rejection or delay in processing and responding to the submission.

Contains Nonbinding Recommendations

The attribute submission-sub-type is used to further clarify the purpose of the submission. The following are the current valid submission-sub-type codes for the submission-type "Promotional Labeling Advertising":

* Original — Use this submission-sub-type for all promotional materials submitted in fulfillment of the postmarketing reporting requirements (2253 submissions) and for materials that do not have a submission history with FDA. This includes original promotional materials such as voluntary requests for advisory comments on launch materials or non- launch materials, and presubmission of promotional materials for accelerated approval products. Also use this code for responses to untitled letters, warning letters, and information requests and for other general correspondence if no submission history with FDA exists for the materials.

* Resubmission — Use this submission-sub-type for voluntary requests for advisory comments and presubmissions of revised promotional materials that were previously submitted as an "original" submission. Do not use this submission-sub-type for any 2253 submissions.

* Amendment — Use this submission-sub-type for a submission that contains additional supportive material to augment information previously submitted, e.g., the submission of promotional material that was previously missing or rejected, withdrawal requests, and submissions of annotated references. In addition, use this submission-sub-type for responses to untitled letters, warning letters, and information requests and for general correspondence if there was an original submission to FDA in eCTD format.

Table 3 summarizes the submission process and the submission-sub-type code for new submissions. The submission history is defined by the format through which the original submission was made. For example, if a 2253 submission was received in paper format (or on a CD in non-eCTD format), the entire submission is considered to be "paper," and all subsequent submissions related to the original 2253 submission (amendments, withdrawal requests, etc.) made prior to the 24 months after publication of this guidance should be made in paper format. FDA will work with firms to determine the appropriate format for subsequent submissions made after 24 months of publication of this guidance to a 2253 submission originally received in paper format. If a submission is received in eCTD format, all subsequent submissions related to the submission should be made in eCTD format.

Table 3: Submission Process and Coding

Submission History	Action	Code for Submission-Sub-Type
Has no prior FDA submission history	Submit to the eCTD with the same submission-id as the sequence number	* “Original”
All promotional materials submitted in fulfillment of the postmarketing reporting requirements (2253 submissions)	Submit to the eCTD with the same submission-id as the sequence number	* “Original”
Already has an associated eCTD promotional submission	Submit to the eCTD with the same submission-id as the original promotional submission	* “Resubmission” for resubmissions<br/>* “Amendment” for amendments; withdrawal requests; reference documents; responses to untitled letters, warning letters, and information requests; and general correspondence
Has a paper-copy submission history only	Do not submit to the eCTD*	* Resubmissions: Submit using paper-copy process<br/>Amendments; withdrawal requests; reference documents; responses to untitled letters, warning letters, and information requests; and general correspondences: Submit using paper copy process.

* FDA will work with firms to determine the appropriate format for subsequent submissions made after 24 months of publication of this guidance to a 2253 submission originally received in paper format. If a submission is received in eCTD format, all subsequent submissions related to the submission should be made in eCTD format.

C. Form Element

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, use form-type Form FDA 2253 (Transmittal of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use) and submit this form in section 1.1. For cases where promotional material(s) mention multiple products, include the attachment listing the other referenced products as a separate leaf title with Form FDA 2253 in section 1.1. Do not include Form FDA 356h for submissions to OPDP or APLB.

Contains Nonbinding Recommendations

D. Promotional Audience Type

When providing information in module 1.15, reference the leaves at the lowest heading elements. For example, the m-1-15-promotional-material heading element needs an attribute of promotional-material-audience-type. When a leaf is referenced in any subsection of module 1.15, provide the attribute as a coded value from its corresponding attribute list (promotional-material-audience-type.xml).

The current valid codes for promotional-material-audience-type are as follows:

Consumer — for promotional materials directed to consumers
Professional — for promotional materials directed to health care professionals

E. Correspondence Related to Promotional Materials (Section 1.15.1)

Submit the correspondence relating to promotional materials as an individual portable document format (PDF) file in the appropriate subsection of 1.15.1. Firms will need to submit a correspondence for all submission types listed in section 1.15.1. A separate cover letter should not be submitted in section 1.2. Please note that firms should not submit a correspondence or a cover letter with 2253 submissions. In some cases, the correspondence may be the actual response and the only file necessary for the submission (e.g., response to untitled letter, response to an Agency communication, or a general correspondence). Correspondence submitted to section 1.15.1 should include the following:

Subject line describing the reason for the submission, the NDA/ANDA/BLA number, the proprietary name/established name (dosage form), and the name of the TV ads (if applicable)

Examples of acceptable descriptions to be included in the subject line include the following:

Request for Comments on Launch Materials
Request for Comments on Non-Launch Materials
Presubmission of Launch Promotional Materials for Accelerated Approval Product
Presubmission of Non-Launch Promotional Materials for Accelerated Approval Product
Response to Untitled Letter
Response to Warning Letter
Response to Information Request
Amendment
Withdrawal Request
Submission of Annotated References
General Correspondence

The body of the correspondence should include the following information:

* Regulatory description of the submission.

* Statement that the submission is virus free, with a description of the software (name, version, and company) used to check the files for viruses.

* A list of all promotional materials included in the submission, with the material type, material ID, and description for each item listed.

* A concise description of use of the promotional material(s), if applicable.

* Whether the submission is for a launch or non-launch.

* If the submission is for a launch, whether the promotional materials are core or non-core.

* Whether the submission is subject to the regulations in 21 CFR 314.550 or 21 CFR 601.45.

* Whether the submission is a TV ad.

* If the submission is the initial response to an untitled letter or warning letter, a list of all promotional materials (with the 2253 submission date) for the drug product(s) that contain violations similar to those described in the letter.

* Whether the submission contains health-care-professional-directed materials or consumer- directed materials.

* Where applicable, whether the Agency has previously commented on the promotional material(s); the comment date; and the Marketing, Advertising and Communications Management Information System (MACMIS) number, MA number, or CBER secondary number.

* The name, title, address, phone, fax, and email of the individual the Agency should contact about issues related to the submission. If there are separate regulatory and technical points of contact, please include this information for both individuals.

Contains Nonbinding Recommendations

F. Materials (Section 1.15.2)

1. Attributes

Submit promotional labeling and advertising materials as individual files in an approved file format in section 1.15.2. When providing information in a subsection of module 1.15.2 materials, three attributes are needed: promotional-material-doc-type, promotional-material- type, and material-id. An optional attribute, issue-date, should only be provided when the promotional-material-doc-type is a promotional 2253 submission. The attribute promotional- material-doc-type indicates the purpose of the promotional submission and needs to be provided with the m1-15-2-materials heading element. Provide the attributes as coded values from their corresponding attribute list (promotional-material-doc-type.xml). Table 4 shows the current valid codes for promotional-material-doc-type.

Table 4: Promotional Material Document Types and Descriptions

Promotional Material Document Type	Description
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-Launch	Voluntary submission of non-launch promotional materials for FDA review and comment sent before dissemination or publication
Presubmission Accelerated Launch	Promotional materials intended to be used in the first 120 days after approval that are submitted to FDA before dissemination or publication as required by 21 CFR 314.550 and 601.45
Presubmission Accelerated Non-Launch	Promotional materials intended to be used after the 120-day postapproval period that are submitted to FDA before dissemination or publication as required by 21 CFR 314.550 and 601.45

The attribute promotional-material-type indicates the type of media/delivery method of the promotional material and should be provided with the m-1-15-2-1 material heading element.

https://www.fda.gov/ectd

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Contains Nonbinding Recommendations

Provide the attributes as coded values from their corresponding attribute list (promotional- material-type.xml).

The material-id attribute may consist of letters, numbers, or both, and should not exceed 30 characters. The issue-date attribute, if applicable, should follow the date format as yyyymmdd (four-digit year, two-digit month, and two-digit day).

Clean Version of Materials Submitted (Section 1.15.2.1.1)

For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 CFR 314.550 or 601.45, submit clean versions of the promotional materials (i.e., versions not including annotations to the label or references) in section 1.15.2.1.1.

Clean versions of corrective pieces should also be submitted in section 1.15.2.1.1, using the eCTD “replace” operation.

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, clean final versions of the promotional materials without any annotations must be submitted in section 1.15.2.1.1.

Annotated Version of Promotional Materials (Section 1.15.2.1.2)

For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 CFR 314.550 or 601.45, submit annotated versions of the promotional materials (i.e., versions that are cross-referenced to the product labeling and, if applicable, references) in section 966 1.15.2.1.2.

Annotated versions of corrective pieces should also be submitted in section 1.15.2.1.2, using the eCTD “replace” operation.

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, firms may choose to submit annotated versions of the promotional materials in section 1.15.2.1.2 that are cross-referenced to the product labeling and, if applicable, references. References improve the efficiency of review.

Firms should highlight and annotate the materials with a cross-reference to the product labeling or references. When product labeling or other references are used to support a claim or presentation in proposed promotional materials, hypertext links should be provided in the annotated promotional material to the specific page that contains the supporting information.

https://www.fda.gov/ectd

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Contains Nonbinding Recommendations

G. Product Labeling (Section 1.14.6 and Section 1.15.2.1.3)

1. Product Labeling Accompanying Form FDA 2253 Submissions (Section 1.14.6)

Form FDA 2253 specifies that the most current product labeling accompany the submission. Firms must submit the most current product labeling, as required in 21 CFR 314.81(b)(3)(i), to section 1.14.6. For promotional labeling pieces, this is the PI that accompanies the promotional materials. The required format for the PI is PDF.

2. Annotated Product Labeling (Section 1.15.2.1.3)

For draft promotional materials submitted (1) voluntarily for advisory comment, or (2) under 21 CFR 314.550 or 601.45, include the annotated product labeling in section 1.15.2.1.3. Firms should highlight and annotate, with a cross-reference to the promotional materials, the sections of the product labeling that are referred to in the promotional materials. When product labeling is used to support a claim or presentation in proposed promotional materials, hypertext links should be provided to the specific page that contains the supporting information.

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, firms may choose to provide the annotated product labeling with hypertext links.

H. Annotated References (Section 1.15.2.1.4)

If references are provided, submit each reference as an individual PDF file and place it in section 1.15.2.1.4. Firms should highlight and annotate, with a cross-reference to the promotional materials, the sections of the full reference that are referred to in the promotional materials. When a reference is used to support a claim or presentation in proposed promotional materials, firms should provide, in the annotated promotional material, hypertext links to the specific page of the reference that contains the supporting information.

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, firms may choose to provide references with hypertext links. References improve the efficiency of review.

I. Including Multiple Promotional Materials in One Submission

For draft promotional materials voluntarily submitted for advisory comment or submitted as required under 21 CFR 314.550 or 601.45, if multiple promotional materials are included in one submission, each of these materials is to be submitted with its own clean version, annotated version, annotated labeling, and annotated references.

The following example shows how to submit multiple promotional materials in one submission in section 1.15 for advisory comments:

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

For promotional materials submitted in fulfillment of the postmarketing reporting requirements, if multiple promotional materials are included in one submission, submit clean versions of each promotional material in section 1.15.2.1.1.

Contains Nonbinding Recommendations

The following example shows how to submit multiple promotional materials in one submission in section 1.15:

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

J. Submission of Promotional Materials Referencing More Than One Application (Grouped Submissions)

Firms are encouraged to submit promotional materials that promote more than one product (i.e., a multiple-product submission) as a grouped submission. However, only one application type can be used in a grouped submission. Therefore, should a promotional material apply to more than one application type (e.g., a BLA and NDA), submit the promotional material as a separate submission for each application type (i.e., there would be two separate submissions—one for the BLA application and one for the NDA application).

K. Leaf Titles

Appropriately named leaf titles allow FDA reviewers to navigate through submissions and distinguish one submission from another in the eCTD viewer. A leaf title should include the MA number if it has been provided in a previous communication with FDA.

The format of the leaf title for the actual form for Form FDA 2253 submissions (placed in section 1.1) should be informative for Agency reviewers. For example, the leaf title "Form FDA 2253 Consumer print ad 20140105" is more informative and searchable than a leaf title of "2253Form." Although both examples identify the submission by type, in the first example the Agency reviewer will know the audience for the promotional material (consumer), the material type code, and the date of the submission—all without having to open the file itself.

https://www.fda.gov/ectd

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In addition, the leaf title for the correspondence related to promotional materials (placed in section 1.15.1) should help the Agency reviewer identify the incoming submission by type. A leaf title of "Response to untitled letter 20140105 MA37" is more informative than a leaf title of "Response to untitled letter," because the former example identifies the type of correspondence, the letter date of the submission, and the MA number.

Leaf titles for each promotional material (placed in section 1.15.2) should also be informative. For example, a health-care-professional-directed sales aid with the leaf title "Sales Aid 65NO35482 Considerations for treatment 20140102" is more informative than the leaf title "promotional material.pdf." When displayed in the eCTD viewer, the first example immediately identifies the material type code, the material identifying number of the piece (if applicable), a description of the piece, and the date of the submission. All of this information is useful to the Agency reviewer, even though there may be some redundancy between information in the leaf title and the materials attributes discussed previously in section VI.F of this guidance.

L. Use of Operator Attributes

When using life cycle operations, use the operator attributes as follows:

* For resubmissions, use the "replace" operator attribute to replace the previously submitted files with the resubmission's updated files. If a firm is only resubmitting part of the original submission, the operator for the correspondence file should be "new."

* For withdrawals, submit the withdrawal request and use the "delete" operator attribute on all leaves that are affected by the withdrawal request. The operator for the correspondence file should be "new."

* For promotional materials submitted in fulfillment of the postmarketing reporting requirements (2253 submissions), if a material previously submitted under cover of Form FDA 2253 is revised, use the "replace" operator attribute to replace the previously submitted files with the revised materials. (The submission-sub-type should be "Original," as indicated in table 3 of this guidance.)

VII. PRESENTATION ISSUES

Because electronic images may not adequately convey the net impression of the promotional material or the details of the intended promotional message within the piece, firms should follow the guidelines in this section to facilitate review by the Agency.

A. General Presentation Considerations

In general, the presentation considerations below encompass the appearance, layout, format, and visible impression of promotional materials submitted for all promotional submission types and audiences. Optimally, Agency reviewers should be able to use or view each promotional material submitted to the Agency in the same manner as the end-user audience. In instances

when this is not possible, firms are to submit electronic promotional materials in a manner for which the net impression is clear and legible; likewise for the individual representations in each promotional material.

Provide each promotional material submitted to the Agency in electronic format as an individual file in an approved file format. If the current list of approved file formats does not allow the firm to submit a fully functional piece, the submission must provide the ability to view all interactive selection options as still images with annotations or notes that clearly describe the functionality of the piece.

Please note that promotional materials submitted with Form FDA 2253 to OPDP must include a representation of the actual piece that is disseminated rather than solely a proof or galley copy of the promotional material. However, a proof or galley copy of the promotional material may also accompany the actual piece as part of the submission in order to demonstrate layout or size presentation elements. Please refer to section VII.K of this guidance for additional details on providing the size or dimensions of materials. Proof or galley copies of the promotional material should be submitted within section 1.15.2.1.2 of module 1.

B. Visibility of Text and Images

Promotional materials should present clear and legible text and images regardless of the format (electronic and/or physical media). Although the Agency recognizes that electronic images and text may require magnification on computer screens during the review process, the majority of images and text within each electronic file should not require excessive magnification in order to obtain the net impression of the piece or an understanding of the individual claims.

C. Concise Description of Use

Each promotional material should include a concise description of use. The description may include, but should not be limited to, the purpose of the piece, setting of use for the piece, and/or an explanation of additional materials that will be used in conjunction with the piece. The concise description of use may be presented on Form FDA 2253 under "Comments," as a comment on the electronic version of the promotional material, as a comment on an optional proof or galley piece, and/or within the correspondence of a voluntary request for comments. A concise description of use is particularly important in situations where additional context is necessary, such as the following:

* The purpose of the promotional material is not self-evident after looking at an image of the piece or reading its title (e.g., a journal ad may be designed with an appearance similar to a booth panel).

* The promotional material is designed for use only in conjunction with other specific promotional materials.

Contains Nonbinding Recommendations

* The promotional material is designed for use in a very specific setting.

* The promotional material (with the same material ID number) is designed for multiple uses in different and unique settings.

Concise descriptions of use may include, but should not be limited to, language such as:

* Booth panel A will be used only in conjunction with booth panels B, C, and D.

* For use as a journal ad and a physician leave-behind.

* Item 1 of 5 of kit.

* For one-time use during [Conference Title, Month/Year].

D. Layout Indicators

Firms should submit promotional materials with clear and legible indicators for navigating through each promotional material, as applicable. Indicators describing location and navigation elements in the piece should be presented on each electronic page or image and should not obstruct the image of the promotional materials. Indicators may include, but should not be limited to, the following:

* Front cover, back cover, inside front cover, inside back cover

* Bottom of piece or page, top of piece or page

* Front of piece, back of piece

* Page numbers

* Inserts

* Pockets and pocket content

* Tabs or section dividers

* Folds

* Blank pages or panels

* Annotations to references

* Actual size

* Clarifying the PI position

Indicators may be presented as symbols or text. A key should be provided (e.g., along the margin of the piece) if symbols are presented as indicators within a submission.

E. Websites, Electronic Interactive Programs, and Electronic Detail Aids

Electronic promotional material submissions including, but not limited to, websites, electronic interactive programs, and electronic detail aids should clearly display and communicate how the

promotional material will look and convey messages to the end user. Preferably, the submission

should allow FDA reviewers to view and interact with the piece in the same manner as the end

user. For example, static electronic images may not adequately convey how complex interactive

promotional materials convey promotional messages. Such promotional submissions may also

Contains Nonbinding Recommendations

be accompanied by a video showing manipulation of the promotional program or application. Also see the eCTD Technical Conformance Guide for additional considerations related to submitting websites and other electronic promotional materials in the eCTD.

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 then updates one page or section of the website, the firm need only submit the updated page or section with a cross-reference to the original submission of the website noted on Form FDA 2253, including the date of the original submission. If the website is substantially revised, the firm must submit the revised website in its entirety.47,48

F. Materials Requiring Physical Manipulation by the End User

Promotional materials requiring physical manipulation by the end user to obtain the net impression of the promotional message (and/or the details of the promotional message) should be submitted in a format that allows the Agency to view all aspects of the promotional material. For example, the electronic submission of a lenticular refrigerator magnet may display one image if tilted left and an alternate image if tilted right. Representations for both images should be submitted in this case.

G. Three-Dimensional Promotional Materials

Electronic submission of three-dimensional promotional objects should provide sufficient detail to allow FDA to view the promotional material from all possible views. In addition, images should provide adequate information to allow Agency reviewers to determine the size of the object (e.g., point size, dimensions). In rare situations, it may not be possible to accurately represent the promotional material in an electronic format. In these situations, the best possible electronic image should be submitted electronically, and a courtesy copy of the promotional material can also be sent for the reviewer. The courtesy copy of the promotional material should be submitted as a general correspondence and should include a reference to the electronic submission and sequence number.

https://www.fda.gov/ectd

.

Contains Nonbinding Recommendations

H. Multi-Page Spreads

Promotional materials that include text or images that span more than one page or for which the promotional message may be interpreted as spanning more than one page (e.g., a two- or three- page brochure spread) should include a clear image or representation of the entire spread within a single view. All possible spreads of a given promotional material should be presented. In addition, electronic images of print materials and electronic materials should be presented in a manner and sequence as they would appear to the end user.

I. Kits

Electronic submission of kits should clearly indicate the components of the kit. Components of the kit that are not intended for distribution apart from the kit should be labeled as such. The accompanying Form FDA 2253 must include the material ID number or identifier for the kit, as well as the material ID number or identifier for each individual component of the kit.

J. Dimensions

All images of physical materials should include dimensions. Acceptable methods to identify dimensions include, but are not limited to, photographs of materials placed next to rulers, annotations on PDF images, or prominent PDF bookmarks identifying the dimensions of a piece. Images of three-dimensional pieces should be identified as such in the descriptions and should provide information adequate to determine height, width, and depth dimensions.

Dimensions should be presented with standard units of measure.

K. Examples of Appropriately Submitted Promotional Materials

Although not exhaustive, the following examples illustrate appropriate electronic submissions of promotional materials in terms of presentation issues:

Example 1: A firm creates a website for a new product that includes links and videos — As part of its postmarketing requirements, the firm must submit an electronic version of the product website under cover of Form FDA 2253. The firm consults the eCTD Technical Conformance Guide and the Specifications for File Format Types Using eCTD Specifications for additional considerations regarding submitting websites in acceptable formats. The submission should allow the FDA reviewer to click on links within the website and view

https://www.fda.gov/ectd

.

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

.

videos or other animations as an end user will experience while using the site. If the firm is unable to provide active links within the electronic submission, the firm should provide electronic images of each web page in conjunction with videos.

Example 2: A firm is disseminating an electronic version of a promotional labeling piece containing a health-care-professional-directed quiz. As part of its postmarketing requirements, the firm should submit an electronic working version of the quiz under cover of Form FDA 2253. If the firm is unable to provide a working version of the quiz, the submission must include images that convey the results of selecting correct answers as well as the images resulting from incorrect answers.

Example 3: A firm voluntarily submits, for comments, an electronic image of a promotional mug that displays a product logo, a frequently used tagline, and a graphic that appears on the mug when hot liquid is added. The submission should include images of the front, back, inside, bottom, and sides of the mug, regardless of whether any particular view contains a promotional claim or representation. In addition, the submission should also include images of the mug when hot liquid is added, along with an explanation of when the images appear. Such a submission would benefit from layout indicators such as "front," "back," and "intentionally left blank," in addition to measurement indicators.

Example 4: A firm voluntarily submits, for comments, an electronic image of a trifold branded print brochure. The firm should present, in the following order, images of (1) the front cover of the brochure, (2) all possible two-page spreads when the brochure is partially opened, (3) the single three-page spread when the brochure is completely opened, and (4) the back cover of the brochure. Such a submission would benefit from layout indicators such as "front panel," "rear panel," "2-panel spread," and "3-panel spread," in addition to measurement indicators.

Example 5: A firm is developing a kit that includes consumer-directed promotional materials that are exclusive to the kit to be submitted for voluntary comments — For each piece of material included in the kit, the firm should provide a concise description for use. For example, a promotional material that is intended only for distribution within the kit would include the following description: "Intended for distribution in consumer-directed sample kit only."

Example 6: A firm is developing a Form FDA 2253 submission for an electronic banner used within an exhibit booth. The firm should submit a working version of the banner. However, if a working version of the banner cannot be submitted, the firm should submit a video of the banner in conjunction with screen shots. This is preferable to a submission consisting only of static screen shots. For example, the submission should include a video of the banner along with screen shots that convey how the message will scroll, the time lapse for the complete scroll of the message, and any variation in the rate that the message is scrolled across a screen.

Contains Nonbinding Recommendations

Example 7: A firm is developing a Form FDA 2253 submission for a consumer-directed branded video game that is embedded within a standard website. If a working version of the game cannot be submitted using an acceptable file format, the firm should submit a video of the game being played in addition to electronic still images of the game. If the game will also be available to consumers within a conference exhibit setting, the firm should include a concise description of use disclosing this additional unique setting.

VIII. PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

The time required to complete this information collection is estimated to average the following:

* 51 hours for promotional labeling voluntarily submitted for comments, including resubmissions and amendments * 3 hours for general correspondence submitted to FDA * 3 hours for requests to withdraw a previous submission to FDA * 13 hours for responses to untitled or warning letters * 13 hours for responses to information requests * 13 hours for reference documents * 13 hours for complaints submitted to OPDP

These estimates include the time to review instructions, search existing data sources, gather the data needed, and complete and review the information collection. Send comments regarding this burden estimate or suggestions for reducing this burden to:

Office of Prescription Drug Promotion, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Bldg. 51, Rm. 3374, Silver Spring, MD 20993-0002

This guidance also refers to previously approved collections of information found in FDA regulations and collections of information that are currently under OMB review. The collections of information in 21 CFR 202.1, including voluntary requests for advisory comments, resubmissions, and amendments for advertisements, have been approved under OMB control number 0910-0686; the collections of information in 21 CFR 601.45 (presubmission of promotional materials for accelerated approval products under part 601) have been approved under OMB control number 0910-0338; the collections of information for Form FDA 2253 and the presubmission of promotional materials for accelerated approval products under 21 CFR part 1344 314 have been approved under OMB control number 0910-0001.

An Agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is 0910-0001. To find the current expiration date, search for this OMB control number at

https://www.reginfo.gov

.

Footnotes

[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 (page 5)

[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). (page 5)

[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 ( U.S.C. 355). See section 351(j) ( 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 (page 5)

[4] See CFR 10.115(d). (page 6)

[5] In the Federal Register of May 31, 2002 ( 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. (page 7)

[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 (page 7)

[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 months after the issuance of this guidance). (page 7)

[8] See 21 CFR 1.3(a). (page 8)

[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. (page 9)

[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. (page 9)

[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 FDA’s current thinking on this topic. (page 10)

[12] The most current version of Form FDA 2253 and Form FDA 2253 Instructions Supplement can be found at (page 10)

[13] Do not include Form FDA 356h for submissions to OPDP or APLB. (page 10)

[16] FDA may determine that the materials submitted do not meet the definition of core materials if they exceed content or page limitations. (page 13)

[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. (page 13)

[18] The document on Specifications for File Format Types Using eCTD Specifications is in the eCTD Submission Standards on the FDA eCTD website at (page 15)

[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." (page 15)

[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 CFR 314.70(a)(4) or CFR 601.12(a)(4). If this type of correspondence is submitted, the recommended subject line is "General Correspondence – Intent to Comply." (page 16)

[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. (page 17)

[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 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. (page 17)

[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. (page 19)

[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. (page 21)

[25] Form FDA 356h is titled “Application to Market a New or Abbreviated New Drug or Biologic for Human Use.” (page 21)

[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. (page 21)

[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. (page 22)

[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. (page 24)

[29] The eCTD module 1 specifications discussed in this section can be located in the eCTD Submission Standards on the FDA eCTD website at (page 24)

[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. (page 24)

[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. (page 24)

[32] The date format to be used is yyyymmdd (four-digit year, two-digit month, and two-digit day). (page 25)

[33] Please refer to section VI.J of this guidance regarding submitting promotional materials that reference more than one application. (page 27)

[34] Please refer to section VI.K of this guidance for a detailed description of leaf titles. (page 27)

[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. (page 28)

[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. (page 30)

[38] The Specifications for File Format Types Using eCTD Specifications is in the eCTD Submission Standards on the FDA eCTD website at (page 30)

[39] The date format to be used is yyyymmdd (four-digit year, two-digit month, and two-digit day). (page 30)

[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 (page 31)

[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. (page 32)

[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. (page 32)

[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. (page 32)

[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 (page 34)

[45] Proof or galley copies are samples or preliminary versions of promotional material created for review and/or proofreading by the firm. (page 36)

[46] The eCTD Technical Conformance Guide is available on the FDA eCTD website at (page 38)

[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. (page 38)

[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 FDA's current thinking on this topic. (page 38)

[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. (page 39)

[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 (page 39)

[51] The eCTD Technical Conformance Guide is available on the FDA eCTD website at (page 39)

[52] A fully functional website should be submitted in an accessible format whenever possible. Firms should not send links to websites—even if they are password-protected. (page 40)

Providing Regulatory Submissions in Electronic and Non-Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs

Providing Regulatory Submissions in Electronic and Non-Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs

Providing Regulatory Submissions in Electronic and Non-Electronic Format — Promotional Labeling and Advertising Materials for Human Prescription Drugs

Guidance for Industry

Providing Regulatory Submissions in Electronic and Non-Electronic Format — Promotional Labeling and Advertising Materials for Human Prescription Drugs

Guidance for Industry

TABLE OF CONTENTS

Providing Regulatory Submissions in Electronic and Non-Electronic Format — Promotional Labeling and Advertising Materials for Human Prescription Drugs

Guidance for Industry

I. INTRODUCTION

II. BACKGROUND

A. Electronic Submissions to FDA Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act

IV. CONTENT FOR SPECIFIC TYPES OF SUBMISSIONS

Contains Nonbinding Recommendations

C. Promotional Materials Submitted Voluntarily for Advisory Comments

1. Requests for Comments on Draft Promotional Materials Other Than DTC TV Ads Under 21 CFR 202.1(j)(4)

D. Resubmissions

Contains Nonbinding Recommendations

F. Amendments (Submission of Previously Missing or Rejected Materials)

A. Submitting Paper Copy Promotional Materials to OPDP

B. Submitting Paper Copy Promotional Materials to APLB

VI. FORMAT FOR SUBMISSION OF PROMOTIONAL MATERIALS ELECTRONICALLY

C. Form Element

D. Promotional Audience Type

E. Correspondence Related to Promotional Materials (Section 1.15.1)

I. Including Multiple Promotional Materials in One Submission

Contains Nonbinding Recommendations

D. Layout Indicators

E. Websites, Electronic Interactive Programs, and Electronic Detail Aids

VIII. PAPERWORK REDUCTION ACT OF 1995

Footnotes