eCTD 

TECHNICAL CONFORMANCE GUIDE

Technical Specifications Document

This Document is incorporated by reference into the following

Guidance Document(s):

Guidance for Industry Providing Regulatory Submissions in Electronic Format — Certain Human

Pharmaceutical Product Applications and Related Submissions Using the

eCTD Specifications

For questions regarding this technical specifications document, contact CDER at 

esub@fda.hhs.gov or CBER at esubprep@fda.hhs.gov

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)

Novemember 2022
eCTD

TECHNICAL CONFORMANCE GUIDE

November 2022
REVISION HISTORY

DATE VERSION SUMMARY OF REVISIONS

October 2015 1.0 Initial Version

September 2016 1.1

Updated/Clarified following sections: 

Section 2.3 (Transitioning to eCTD Format and Resubmission of Non- eCTD

Documents), and subsections 2.3.1, 2.3.2, 2.3.3, 2.3.4

Section 2.4 (eCTD Leaf Titles) 

Section 2.6 (Presubmissions) 

Section 2.7 (Rolling Submission) 

Section 3.1.2 (Cover Letter and Reviewer’s Guide) 

Section 3.1.7 (Information Amendments) 

Section 3.1.8 (Letters of Authorization) 

Section 3.1.9 (Field Copy Certification) 

Section 3.5.2 (Study Reports) 

Section 4.1 (Combining Multiple 3.2.S or 3.2.P Sections with Similar Metadata)

Section 5.0 (Combination Products) 

References

Removed section: 

Section 3.3.4 (Datasets)

Added sections: 

Section 2.3.4 (Resubmission of non-eCTD documents )

Section 3.1.5.3 (Websites, Electronic Interactive Programs, and Electronic Detail Aids)

November 2017 1.2

Updated/Clarified following sections:

Section 2.3.3 (Transitioning from us-regional v2.01 to us-regional v3.3)

Section 2.3.4 (Resubmission of non-eCTD documents)

Section 2.5 (eCTD Life Cycle)

Section 3.1.2 (Cover Letter and Reviewer’s Guide)

Section 3.4.3 (Datasets)

Section 3.5.2 (M5 Study Reports)

Section 3.5.4 (Periodic Safety Reports)

Section 3.5.7 (Datasets)

Added sections:

Section 3.1.10 (REMS)

November 2018 1.3

Updated/Clarified following sections:

Section 2.5 (eCTD Submission Tracking and Lifecycle)

Section 2.8 (Study Tagging Files)

Section 3.1.10 (REMS)

Added sections:

3.1.11 (Regenerative Medicine Advanced Therapy Designation)

December 2019 1.4

Updated/Clarified following sections:

Section 3.4 (Module 4 - Nonclinical)

Section 3.5 (Module 5 - Clinical)

Removed section: 

Section 3.1.8 (Letters of Authorization)

Added sections:

2.9 (Master Files)

3.1.3 (Patient Experience Data)
DATE VERSION SUMMARY OF REVISIONS

July 2020 1.5 Updated section:

Section 3.1.10 (REMS)

October 2021 1.6

Updated section:

Section 2.3 (Transitioning to eCTD Format and Resubmission of non-eCTD Documents)

Removed subsection “Transitioning from Paper to eCTD using us-regional 

v2.01”

Section 3.1.1 (FDA Regional eCTD Backbone Files)

Section 3.1.6 (Advertisements and Promotional Labeling Material)

Added section:

Section 3.5.8 (aECG Waveform)

March 2022 1.7

Updated/Clarified following sections:

Section 2.3.2 (Transitioning from us-regional v2.01 to us-regional v3.3)

Section 3.1.1 (FDA Regional eCTD Backbone Files)

Section 3.1.6 (Advertisements and Promotional Labeling Material)

Removed sections: 

Section 3.1.6.1 (Advertisements and Promotional Labeling to CDER)

Section 3.1.6.2 (Advertisements and Promotional Labeling to CBER)

Section 3.1.6.2.1 (Using version 2.01 of the us-regional.xml file)

Section 3.1.6.2.2 (Using version 3.3 of the us-regional.xml file)

Section 3.1.6.3 (Websites, Electronic Interactive Programs, and Electronic Detail Aids)

November 2022 1.8 Added section:

Section 3.3.3 (Structure-Data Files)
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Table of Contents

1. INTRODUCTION................................................................................................................................... 1

1.1 BACKGROUND .......................................................................................................................................... 1

1.2 PURPOSE ................................................................................................................................................. 1

1.3 DOCUMENT REVISION AND CONTROL............................................................................................................ 2

1.4 RELATIONSHIP TO OTHER DOCUMENTS ......................................................................................................... 2

2. GENERAL CONSIDERATIONS.......................................................................................................... 3

2.1 ECTD PUBLISHING..................................................................................................................................... 3

2.2 ECTD SAMPLES ........................................................................................................................................ 3

2.3 TRANSITIONING TO ECTD FORMAT AND RESUBMISSION OF NON-ECTD DOCUMENTS ............................................ 3

2.3.1 Transitioning from Paper to eCTD using us-regional v3.3...................................................... 3

2.3.2 Transitioning from us-regional v2.01 to us-regional v3.3...................................................... 3

2.3.3 Resubmission of non-eCTD documents.................................................................................. 4

2.4 ECTD LEAF TITLES..................................................................................................................................... 4

2.5 ECTD SUBMISSION TRACKING AND LIFE CYCLE................................................................................................ 5

2.6 PRESUBMISSIONS ...................................................................................................................................... 5

2.7 ROLLING SUBMISSIONS............................................................................................................................... 5

2.8 STUDY TAGGING FILES................................................................................................................................ 6

2.9 MASTER FILES .......................................................................................................................................... 6

3. ORGANIZATION OF THE ECTD ...................................................................................................... 7

3.1 MODULE 1 – ADMINISTRATIVE INFORMATION AND PRESCRIBING INFORMATION................................................... 7

3.1.1 FDA Regional eCTD Backbone Files........................................................................................ 7

3.1.2 Cover Letter and Reviewers Guide ......................................................................................... 7

3.1.3 Patient Experience Data......................................................................................................... 8

3.1.4 Cross Referencing Previously Submitted Information that is not in eCTD Format................. 8

3.1.5 Labeling.................................................................................................................................. 8

3.1.6 Advertisements and Promotional Labeling Material ........................................................... 10

3.1.7 Marketing Annual Reports................................................................................................... 10

3.1.8 Information Amendments.................................................................................................... 10

3.1.9 Field Copy Certification ........................................................................................................ 11

3.1.10 Risk Evaluation and Mitigation Strategy (REMS)................................................................. 11

3.1.11 Regenerative Medicine Advanced Therapy (RMAT) Designation ........................................ 13

3.2 MODULE 2 – SUMMARIES ........................................................................................................................ 13

3.2.1 Bioequivalence Summary Tables.......................................................................................... 13

3.3 MODULE 3 – QUALITY ............................................................................................................................. 13

3.3.1 Lot Distribution Data............................................................................................................ 13

3.3.2 Literature References........................................................................................................... 13

3.3.3 Structure-Data Files ............................................................................................................. 13

3.4 MODULE 4 – NONCLINICAL....................................................................................................................... 14

3.4.1 Study Reports....................................................................................................................... 14

3.4.2 Literature References........................................................................................................... 14

3.4.3 Datasets............................................................................................................................... 14

3.5 MODULE 5 – CLINICAL ............................................................................................................................. 15

3.5.1 Tabular Listing of All Clinical Studies.................................................................................... 15

3.5.2 Study Reports....................................................................................................................... 15

3.5.3 Case Report Forms (CRFs) .................................................................................................... 16

3.5.4 Periodic Safety Reports........................................................................................................ 16

3.5.5 IND Safety Reports............................................................................................................... 16

3.5.6 Literature References........................................................................................................... 17
ii

3.5.7 Datasets............................................................................................................................... 17

3.5.8 aECG Waveform................................................................................................................... 17

4. ISSUES AND SOLUTIONS................................................................................................................. 18

4.1 ISSUE: COMBINING MULTIPLE 3.2.S OR 3.2.P SECTIONS WITH SIMILAR METADATA ........................................... 18

4.2 ISSUE: CLINICAL STUDY REPORT SUBMITTED IN INCORRECT SECTION ................................................................. 18

4.3 ISSUE: NOT APPLICABLE (N/A) OR UNASSIGNED FOLDERS IN MODULE 4 OR 5.................................................... 18

4.4 ISSUE: MULTIPLE SIMILAR STF STRUCTURES DISPLAYING IN MODULE 4 OR 5 ..................................................... 19

5. COMBINATION PRODUCTS............................................................................................................ 20

REFERENCES ............................................................................................................................................... 24

RELATED REFERENCES........................................................................................................................... 25
Contains Nonbinding Recommendations

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eCTD TECHNICAL CONFORMANCE GUIDE

This technical specifications document represents the current thinking of the Food and 

Drug Administration (FDA or Agency) on this topic. It does not create 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 staff responsible for implementing 

this specifications document by email at esub@fda.hhs.gov or esubprep@fda.hhs.gov.

1. Introduction

1.1 Background

This eCTD Technical Conformance Guide (Guide) provides specifications, 

recommendations, and general considerations on how to submit electronic Common 

Technical Document (eCTD)-based electronic submissions to the Center for Drug 

Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research 

(CBER). The Guide supplements the guidance for industry Providing Regulatory 

Submissions in Electronic Format — Certain Human Pharmaceutical Product 

Applications and Related Submissions Using the eCTD Specifications (eCTD Guidance).1

 

The eCTD Guidance implements the electronic submission requirements of section 

745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) with respect to 

electronic submissions for certain investigational new drug applications (INDs); new 

drug applications (NDAs); abbreviated new drug applications (ANDAs); certain 

biologics license applications (BLAs); and master files submitted to CDER or CBER. 

These submissions may apply to combination products with CDER or CBER as the lead 

center.2

1.2 Purpose

This Guide provides technical recommendations to sponsors and applicants for the 

standardized electronic submission format of INDs, NDAs, ANDAs, BLAs, and master 

files. The Guide is intended to complement and promote interactions between sponsors 

and applicants and FDA’s electronic submission support staff. However, it is not 

intended to replace the need for sponsors and applicants to communicate directly with 

support staff regarding implementation approaches or issues relating to electronic 

submissions.

Because of the inherent variability across studies and applications, it is difficult to 

identify all issues that may occur related to the preparation and transmission of electronic 

submissions. Therefore, prior to submission, sponsors and applicants should discuss 

questions with the appropriate center’s electronic submission support staff within the 

appropriate center — CDER: esub@fda.hhs.gov or CBER: esubprep@fda.hhs.gov. 

1 A link to this document can be found on the FDA eCTD website (https://www.fda.gov/ectd) 2 See 21 CFR Part 3. Combination products are comprised of any combination of a drug and a medical 

device; a medical device and a biological product; a biological product and a drug; or a drug, a medical 

device, and a biological product. Combination products are assigned to a lead center for review; see 21 

CFR 3.4.
Contains Nonbinding Recommendations

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1.3 Document Revision and Control

FDA issued an initial Federal Register notice announcing availability of this Guide for 

public comment on its contents. Future revisions will be posted directly on the eCTD 

website3 and the revision history page of this document will contain sufficient 

information to indicate which sections of the Guide have been revised.

1.4 Relationship to Other Documents

This Guide integrates and updates information discussed previously in the eCTD 

Guidance and other specifications documents (including Agency presentations).

 The 

examples of issues and concerns discussed in the Guide are intended as examples only 

of common issues, not an inclusive list of all possible issues.

This Guide should be considered a companion document to the following:

• Guidance to Industry Providing Regulatory Submissions in Electronic Format —

Certain Human Pharmaceutical Product Applications and Related Submissions 

Using the eCTD Specifications

• FDA eCTD Website

• FDA Data Standards Catalog

• eCTD Submission Standards

3 FDA eCTD website (https://www.fda.gov/ectd)
Contains Nonbinding Recommendations

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2. General Considerations

2.1 eCTD Publishing

Submissions in the eCTD format should be created following all applicable guidances 

and specifications available on our eCTD website: 

https://www.fda.gov/ectd.

2.2 eCTD Samples

Samples of eCTDs can be submitted for feedback on document placement, navigation, 

and effective use of metadata and Study Tagging Files (STFs). For eCTD samples and 

instructions, please refer to our eCTD Basics and Getting Started website located at: 

https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/submit-ectdor-standardized-data-sample-fda

2.3 Transitioning to eCTD Format and Resubmission of non-eCTD Documents

When transitioning to eCTD format, you are not required to resubmit documents already 

submitted in paper or other electronic format. Provide only new or changed information

and begin with sequence number 0001. For example, if your original application was 

submitted in paper and now a supplement will be submitted to the application in eCTD 

format, you should not resubmit electronic copies of documents and eCTD backbone 

files for the previously submitted paper files. For INDs, there is no requirement to match 

up the sequence number with the serial number.

2.3.1 Transitioning from Paper to eCTD using us-regional v3.3

The initial eCTD submission utilizing us-regional v3.3 should be coded according to the 

current regulatory activity. The submission-id should match the sequence number of the 

transition sequence. To transition an IND, master file, or an original ANDA, BLA, 

NDA, the transition submission should be coded as “original application” for the 

submission-type and “application” for submission-subtype. If the original application 

has been approved and a supplement or annual report is the current regulatory activity, 

code the transition sequence as the appropriate supplement type or as annual report. To 

transition with the submission of a new supplement or annual report, the submission 

type should be coded with the appropriate supplement type (e.g., submission-type = 

labeling supplement/ submission-subtype = application) or as a new annual report (e.g., 

submission-type = annual report / submission-subtype = report).

2.3.2 Transitioning from us-regional v2.01 to us-regional v3.34

The initial eCTD submission should be coded according to the current regulatory 

activity. If the submission is updating a regulatory activity started in us-regional v2.01, 

the submission-id in us-regional v3.3 should match the sequence number of the initial 

eCTD submission to that regulatory activity. If the submission using us-regional v3.3 is 

creating a new regulatory activity, the submission-id should match the sequence 

number. If the v3.3 submission is amending a regulatory activity where that submission 

type does not exist in v2.01 but does exist in v3.3, set the submission id equal to the 

4 us-regional.xml backbone DTD V2.01 is no longer supported as of March 1, 2022.
Contains Nonbinding Recommendations

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sequence number and use a submission subtype which starts the regulatory activity (e.g., 

submission-type = IND safety report / submission–subtype = report).

2.3.3 Resubmission of non-eCTD documents

In general, resubmission of previously submitted content is neither necessary nor 

encouraged. However, there are occasional circumstances in which a “baseline” 

submission is helpful to the reviewer. One example is CMC information contained in 

module 3. In a circumstance such as this, the FDA will accept the resubmission of noneCTD content (e.g., paper, eNDA) but the previously submitted content should be 

submitted as a separate submission, as opposed to being included in a supplement or an 

amendment to a regulatory activity. The cover letter should state that the submission 

contains only previously submitted content and certify that the sequence does not 

include any changes or updates to the application. For marketing applications, the 

certification should include a table with a listing of approvals that relate to the content 

being resubmitted. For INDs and master files, the list should include amendments that 

relate to the content being resubmitted. 

In most cases, the submission of a “baseline” or other previously submitted content will 

require that the previous content be reorganized to meet the eCTD format requirements. 

You should not resubmit the previous content “as-is”, unless the content was in the CTD 

format but you did not use the eCTD backbone when content was originally submitted.

The submission-type should be coded as “product correspondence”. On the 356h form, 

you should select “Product Correspondence” for the Submission type and enter 

“Submission of previous non-eCTD content in the eCTD format”.

Prior to resubmitting content, you should contact the responsible review division to 

determine if resubmission is acceptable.

2.4 eCTD Leaf Titles

Leaf titles for eCTDs are displayed to the reviewer when viewing an eCTD application. 

Although some eCTD tools generate leaf titles that are similar to file names, the two are 

not related. All modules of the eCTD should contain descriptive eCTD leaf titles that 

are short, meaningful, and indicative of each document's content. You should not 

include the eCTD section number in the leaf title.

For documents of the same type (such as the cover letter, Form FDA 356h, and annual 

report documents), you should provide additional information in the eCTD leaf title so 

reviewers can distinguish documents submitted in different sequences. For example, the 

leaf title for a cover letter should also include the date or sequence number (e.g., coverletter-2015-12-31 or cover-letter-0001). Additionally, if documents of the same type are 

being provided in different file formats, a file format (e.g., “MS Word”) should be 

included at the end of the leaf title. This helps reviewers to quickly identify which 

software applications are necessary to open the files.
Contains Nonbinding Recommendations

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Per eCTD Guidance (Providing Regulatory Submissions in Electronic Format —

Certain Human Pharmaceutical Product Applications and Related Submissions Using 

the eCTD Specifications), when naming folders and files, the length of the entire path 

must not exceed 150 characters. The character limit on the leaf title field is 512 

characters.

2.5 eCTD Submission Tracking and Life Cycle

The rules for submission tracking information (i.e., the allowable submission types for 

the application) can be found in the Module 1 specification.

5

Refer to published specifications for descriptions and details regarding life cycle 

operation attributes.6

 For life cycle of STF (Study Tagging File), please reference the 

STF specification.

7

Please note: The use of "append" is not common. You should avoid appending multiple 

documents to a single leaf and consider consolidating the information and using the 

“replace” life cycle attribute to update the original file. However, it may be appropriate 

if, for example, you are adding a single page of information to a lengthy document. 

Updated datasets should “replace” the old dataset. Do not use “append” when updating 

datasets.

2.6 Presubmissions 

Any information submitted in eCTD format before the “original-application” should be 

coded as "presubmission" and should start with sequence 0001. A high submission 

sequence series (e.g., 9000) should not be used. Code as submission-type “original 

application” and submission-subtype “presubmission”. The original application will use 

the next available sequence number depending on the number of submitted 

“presubmissions”. 

2.7 Rolling Submissions

Rolling submissions for NDAs and BLAs are managed the same as presubmissions to the 

application until the application is complete and ready for review. The cover letter and 

form should state “presubmission to rolling submission – part 1 of XXX” (depending on 

how many parts before the final submission). The final submission completing the 

application should be coded as “original-application” to start the respective review clock. 

The cover letter and form of the final submission should state “original application – part 

XXX of XXX of rolling submission”.

The rolling submission should be coded as submission-type “original application” with 

5 The eCTD Backbone Files Specification for Module 1 can be accessed through the eCTD Submission 

Standards catalog. The catalog is located on the FDA eCTD website (https://www.fda.gov/ectd) 6 The ICH Electronic Common Technical Document Specifications v3.2.2 can be accessed 

at:https://www.ich.org/page/ich-electronic-common-technical-document-ectd-v322-specification-andrelated-files

7 The ICH Electronic Common Technical Document Study Tagging File Specification v2.6.1 can be 

accessed through the eCTD Submission Standards catalog. The catalog is located on the FDA eCTD 

website (https://www.fda.gov/ectd)
Contains Nonbinding Recommendations

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submission-subtype “presubmission”. The final submission completing the application 

should be coded as submission-type “original-application” with submission-subtype 

“application”.

2.8 Study Tagging Files

Study Tagging Files (STFs) are required for all files in section 4.2.x and 5.3.1.x –

5.3.5.x.8

 STFs are not required for 4.3 Literature references, 5.2 Tabular listings, 5.3.6 

Postmarketing reports and, 5.4 Literature references. These documents may be submitted 

as single separate files without an STF. 

2.9 Master Files

For information on Drug Master File submissions, including Letters of Authorization,

please refer to the Drug Master File website (https://www.fda.gov/drugs/formssubmission-requirements/drug-master-files-dmfs).

8 This requirement is discussed in the eCTD Guidance available on FDA eCTD website. 

(https://www.fda.gov/ectd)
Contains Nonbinding Recommendations

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3. Organization of the eCTD

3.1 Module 1 – Administrative Information and Prescribing Information

Module 1 contains administrative, labeling, and promotional material documents. The 

subject matter for each document should be assigned to the lowest level of the hierarchy 

outlined in the associated FDA technical specification Comprehensive Table of Contents 

Headings and Hierarchy available on our eCTD website.

9 (Note that some headings 

apply only to specific applications or specific submissions.) 

3.1.1 FDA Regional eCTD Backbone Files

Submissions to CDER and CBER require us-regional.xml backbone version 3.3. 

If you are unable to acquire a DUNS number prior to submission, you may enter 

999999999.

3.1.2 Cover Letter and Reviewers Guide

Cover Letter

Cover letters contain pertinent information which aid communication within the review 

process. It is recommended that the cover letter include the following information: 

• Regulatory description of the submission, including appropriate regulatory 

information, and any desired hyperlinks to submitted information 

• Technical description of the submission, including the approximate size of the

submission (e.g., 2 gigabytes)

• Statement that the submission is virus free, with a description of the software 

(name, version, and company) that was used to check the files for viruses 

• A regulatory and technical point of contact for the submission, including email 

address

Reviewers Guide

A reviewers guide10 is beneficial when accompanying an original NDA, BLA, or 

combination product11 application. The reviewers guide should include a high-level 

overview of the submission with hyperlinks to submitted information. The reviewers 

guide should not contain a copy of the eCTD backbone table of contents. Rather, an

outline format describing the submission's content is preferred, including tables or lists, 

and avoiding a continuous narrative description of the application’s content.

The reviewers guide should be provided as a document separate from the cover letter 

and placed in section 1.2 of the eCTD with a descriptive leaf title.

9 Comprehensive Table of Contents Headings and Hierarchy may be found in the eCTD Submissions 

Standards catalog. The catalog is located on the FDA eCTD website (https://www.fda.gov/ectd) 10 This is different than a Study Data Reviewers Guide (SDRG). Additional information on the SDRG can 

be found in the Study Data Technical Conformance Guide located at: 

https://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm 11 See additional recommendation for combination products in section 5 of this document
Contains Nonbinding Recommendations

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3.1.3 Patient Experience Data

If submitting patient experience data as part of an application for marketing approval, the 

following table should be populated and included in the Reviewer’s Guide (section 1.2). 

Patient experience data (e.g., clinical outcome assessments) collected as part of a clinical 

trial should be submitted as part of the relevant clinical trial data. Other patient 

experience data that is separate from clinical trials should be submitted to section 5.3.5.4.

□ The patient experience data that was submitted as part of the 

application, include:

Section(s) and if 

applicable, file 

names where data 

are located and 

discussed in the 

application

□ Clinical outcome assessment (COA) data, such as

□ Patient reported outcome (PRO)

□ Observer reported outcome (ObsRO)

□ Clinician reported outcome (ClinRO)

□ Performance outcome (PerfO)

□ Qualitative studies (e.g., individual patient/caregiver interviews, 

focus group interviews, expert interviews, Delphi Panel, etc.)

□ Patient-focused drug development or other stakeholder meeting 

summary reports 

□ Observational surveys studies designed to capture patient 

experience data 

□ Natural history studies 

□ Patient preference studies (e.g., submitted studies or scientific 

publications)

□ Other: (Please specify) 

3.1.4 Cross Referencing Previously Submitted Information that is not in eCTD 

Format

If reference to a non-eCTD submission is needed, place a cross reference document 

(e.g., table showing where to find non-eCTD documents) in section 1.4.4. The 

information in the document should include (1) the application number, (2) the date of 

submission (e.g., letter date), (3) the file name (if applicable), (4) the page number (if 

necessary), and (5) the submission identification (e.g., submission number, volume 

number if paper, electronic folder if applicable) of the referenced document.

3.1.5 Labeling

This section describes how to provide specific labeling documents:

Labeling History

A history that summarizes labeling changes should be provided as a single PDF file. 

The history summary should include the following information:
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• Complete list of the labeling changes being proposed in the current submission 

and the explanation for the changes

• Date of the last approved labeling

• History of all changes since the last approved labeling. With each change, note 

the submission that originally described the change and the explanation for the 

change.

• List of supplements pending approval that may affect the review of the labeling 

in the current submission

Content of Labeling 

The FDA guidance for industry Providing Regulatory Submissions in Electronic Format 

— Content of Labeling gives details on providing the content of labeling files. 

Labeling Samples

Each labeling sample (e.g., carton labels, container labels, package inserts) should be 

provided as an individual PDF file. The samples should:

• Include all panels, if applicable

• Be provided in their actual size, and

• Reflect the actual color proposed for use 
Contains Nonbinding Recommendations

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3.1.6 Advertisements and Promotional Labeling Material

As described in the guidance for industry “Providing Regulatory Submissions in 

Electronic and Non-Electronic Format--Promotional Labeling and Advertising Materials 

for Human Prescription Drugs”, certain types of promotional-material-related 

submissions, including postmarketing submissions of promotional materials are required 

to be submitted in eCTD format.

While HTML (a commonly used file type for websites) is an acceptable file format type 

to use for eCTD Module 1 promotional submissions, submission of HTML files that 

depend on JavaScript, PHP or server-side scripts that generate dynamic content should 

not be submitted because these dependent files are not on the list of acceptable file format 

types. An acceptable alternative for these types of HTML files is to utilize PDF. Please 

refer to the PDF Specifications for details.12

3.1.7 Marketing Annual Reports

You should include a bookmark for each study or trial described in the postmarketing 

requirement/commitments files. The reporting period covered by the annual report 

should be included in the eCTD leaf title (e.g. Status of Postmarketing Study 

Commitments - MMDDYY-MMDDYY). 

3.1.8 Information Amendments

Documents for information amendments should be included in the applicable eCTD 

module using the appropriate eCTD heading to describe the document’s subject matter. 

Section 1.11 may be used for submission of responses to Information Requests (IR), 

where the information being submitted does not fit under any heading in Module 2, 3, 4 

or 5. The IR response should be submitted under the appropriate subheading 1.11.1 –

1.11.3 within section 1.11, for quality, nonclinical, or clinical information, respectively. 

The subheading 1.11.4 for multiple module information should be used if the IR 

response covers multiple subject areas.

If the IR response impacts documents submitted in Modules 2 – 5, the new or 

replacement documents should be submitted to the appropriate location in Module 2 –

5 and referenced from Section 1.11.

12 See “Special Considerations for Promotional, Labeling, and Advertising Material” in the Portable

Document Format (PDF) Specifications located in the eCTD Submission Standards catalog. The catalog is 

located on the FDA eCTD website (https://www.fda.gov/ectd)
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3.1.9 Field Copy Certification

For marketing applications, the Field Copy Certification (copy of communication 

described below) should be included with the electronic application in section 1.3.2 of the 

eCTD. You should notify the District office by letter that your eCTD submission will be 

submitted to FDA, and because the field offices have access to the complete submission 

on the FDA network, an individual field copy is no longer required. The letter should 

include: 

• Drug and application number

• FDA center and division

• Application is in eCTD format

3.1.10 Risk Evaluation and Mitigation Strategy (REMS)

A REMS supplement is a supplemental application proposing a new REMS or 

modifications (major and/or minor) to an approved REMS. When submitting a REMS 

supplement use the eCTD submission type of REMS Supplement in the us-regional.xml 

and select REMS supplement on the 356h form.

If new proposed REMS or modifications to an approved REMS is submitted as part of an 

efficacy, CMC, or labeling supplement, the submission type should be coded with the 

appropriate supplement type (e.g., either efficacy, CMC, or labeling). On the 356h form, 

you should select both supplements for the submission type. 

REMS assessments, REMS revisions, and REMS correspondences are not supplements. 

The submission type should be coded as “product correspondence”. On the 356h form, 

you should select “other” for the submission type. 

The following table is provided to assist applicants on placing documents under the 

eCTD Module 1 REMS 1.16 sub-headings of the us-regional.xml file.

eCTD Section: 1.16 Risk Management

eCTD Section 

Heading

Description

1.16.1 Risk

Management

(Non-REMS)

Applicants should place risk management plans (RMP), risk minimization action

plans (RiskMAPs), and RiskMAP reports under this heading. Submission of a Risk

Evaluation and Mitigation Strategy (REMS) should not be placed under this heading 

as REMS are to be included under heading 1.16.2. However, if the applicant is

submitting a rationale for not submitting a proposed REMS, it should be placed here.

1.16.2 Risk

Evaluation and 

Mitigation 

Strategy

(REMS)

Do not include any files under this heading. The files should be specific for the

lowest level of the hierarchy outlined in the FDA technical specification 

Comprehensive Table of Contents Headings and Hierarchy available on our eCTD

website 13and provided below for sub-heading 1.16.2.

13 Comprehensive Table of Contents Headings and Hierarchy may be found in the eCTD Submissions 

Standards catalog. The catalog is located on the FDA eCTD website (https://www.fda.gov/ectd) 
Contains Nonbinding Recommendations

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1.16.2.1 Final 

REMS

The final REMS document, all REMS materials in their final format, and the REMS 

supporting document (for original REMS, REMS modifications, and REMS 

revisions) 14 should be submitted in Microsoft Word and PDF format.

FDA can also accept the REMS document in Structured Product Labeling (SPL) 

format. If you intend to submit the REMS document in SPL format, as soon as 

possible, but no later than 14 days from the approval, submit the REMS document in 

SPL format using the FDA automated drug registration and listing system (eLIST).

For more information on submitting REMS in SPL format, please email

REMS_Website@fda.hhs.gov.

1.16.2.2 Draft

REMS

The proposed REMS document, all REMS materials, and the REMS supporting 

document in clean and track changes (for original REMS, REMS modifications,

and REMS revisions) should be submitted in Microsoft Word format as individual 

files. If certain documents, such as enrollment forms, are only in PDF format, they

may be submitted as such, but the preference is to include as many as possible in 

Word format.

Applicants can also submit the proposed REMS document in SPL format. If you 

intend to submit the proposed REMS document in SPL format, include the SPL file 

with your proposed REMS submission. The REMS SPL file should be referenced in 

the eCTD xml backbone under section 1.16.2.2. The REMS SPL file should be

placed in a folder named “spl”, along with copies of any REMS materials referenced 

in the REMS SPL file.

1.16.2.3 REMS 

Assessment

Applicants REMS assessment report, abbreviated REMS assessment for an 

efficacy supplement, and responses to FDA “Requests for Information or 

Comments” that are associated with an assessment should be placed here.

1.16.2.4 REMS 

Assessment

Methodology

Any survey or other methodology used to assess the REMS should be placed here.

1.16.2.5 REMS 

Correspondence

Official REMS related correspondence to the FDA that is not associated with a 

submission under review should be placed here. Applicants responses to FDA 

“Requests for Information or Comments” that are associated with a REMS

supplement or an assessment that is under review should be included under 

applicable sub-headings.

1.16.2.6 REMS 

Modification 

History

It is recommended that applicants submit a REMS history that summarizes all type

of changes (revisions, minor modifications, and major modifications) made to the

REMS since its approval.

15 The REMS history should be in tabular format similar

to the history of labeling changes and submitted as a single PDF file.

14 See Guidance for Industry Risk Evaluation and Mitigation Strategies: Modifications and Revisions, 

available at: https://www.fda.gov/Drugs/GuidancecomplianceRegulatoryInformation/Guidances/default.htm 15 See Guidance for Industry Risk Evaluation and Mitigation Strategies: Modifications and Revisions, 

available at: 

https://www.fda.gov/Drugs/GuidancecomplianceRegulatoryInformation/Guidances/default.htm

for a more detailed description of the REMS history
Contains Nonbinding Recommendations

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3.1.11 Regenerative Medicine Advanced Therapy (RMAT) Designation

Currently there is no Module 1 section for RMAT designation requests. Therefore, please 

place the RMAT designation request in section 1.12.4 and provide a hyperlink in the 

cover letter to the request. For additional information on the RMAT designation

requirements please refer to https://www.fda.gov/vaccines-blood-biologics/cellular-genetherapy-products/regenerative-medicine-advanced-therapy-designation.

3.2 Module 2 – Summaries

3.2.1 Bioequivalence Summary Tables

For ANDAs, Bioequivalence Summary Tables should be provided in section 2.7.1 of 

the eCTD. Additional information about ANDA submissions is available on the 

ANDA Forms and Submission Requirements Website located at: 

https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/abbreviated-newdrug-application-anda-forms-and-submission-requirements.

3.3 Module 3 – Quality 

3.3.1 Lot Distribution Data

Lot distribution data should be submitted for BLAs according to the guidance for 

industry Electronic Submission of Lot Distribution Reports available at:

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electronicsubmission-lot-distribution-reports.

3.3.2 Literature References

The files pertaining to key literature references should be provided as individual PDF 

files in section 3.3 of the eCTD. The file names and eCTD leaf titles should be short 

and meaningful (e.g., eCTD leaf title: SmithJA 2002 Impurities).

3.3.3 Structure-Data Files

Depending on the needs of the submission, include chemical structures of drug 

substances, drug products, impurities, starting materials, intermediates, metabolites, 

and leachables in Module 3 in a Structure-Data File (SD File). SD File is a nonproprietary file format used to encode chemical structure data using the molfile 

connection table format (J. Chem. Inf. Comput. Sci. 1992, 32, 3, 244–255). This format 

depicts chemical structures using a block of text that lists the atoms, bonds, 

connectivity, coordinates, and attributes. SD File is also commonly called an “.sdf” or 

“SDF.” All SD Files should use .sdf as the file extension and use the v2000 connection 

table format. The Quick Guide to Creating a Structure-Data File (SD File) for 

Electronic Common Technical Document (eCTD) Submission to assist industry in how 

to prepare SD Files and specific details on which section the file(s) should go for 

ANDAs, NDAs, and BLAs is available here: https://www.fda.gov/industry/fdadata-standards-advisory-board/fdas-global-substance-registration-system. A 

Quick Guide to Creating a Structure-Data File (SD File) for DMF Submissions is also 
Contains Nonbinding Recommendations

14

available here: https://www.fda.gov/drugs/gdufa-ii-drug-master-filesdmfs/drug-master-file-dmf-submission-resources.

3.4 Module 4 – Nonclinical 

The organization of Module 4 is the same for all applications and related submissions. 

The documents for Module 4 should be placed in the m4 folder. The subject matter for 

each document should be specific for the lowest level of the hierarchy outlined in the 

FDA technical specification Comprehensive Table of Contents Headings and 

Hierarchy. The headings for study reports should also be specific for the lowest level 

of the hierarchy. Each document should be provided as an individual PDF file. Please 

refer to the Study Data Technical Conformance Guide for additional requirements.

3.4.1 Study Reports

When providing a study report, you should include the Study Tagging File (STF) 

described in the associated ICH M2 technical specification The eCTD Backbone File 

Specification for Study Tagging Files and required by the eCTD Guidance. Individual 

study documents should be referenced in an STF using the appropriate STF ‘file-tag’ 

describing the document’s contents.

Typically, a single document should be provided for each study report included in this 

module. However, if you are providing the study reports as multiple documents, the 

subject matter of each document should be confined to a single item from the list 

provided in the FDA technical specification Comprehensive Table of Contents 

Headings and Hierarchy.

In the following examples, study reports should be provided as separate (granular) 

documents:

1. Documents previously submitted within an application: If a document has 

been provided in a previous submission (e.g., referencing a previously provided 

protocol), the applicant should provide only an eCTD leaf reference to the 

protocol and not resubmit the protocol file.

2. Inclusion of additional information: Study reports should be provided as 

separate documents. Additional information (e.g., audit information or a 

publication based on the study) should be provided as a separate file, rather than 

replacing the entire study report.

3.4.2 Literature References

Each literature reference should be provided as an individual PDF file (not referenced 

by a STF) in section 4.3 of the eCTD. The file names and eCTD leaf titles should be 

short and meaningful (e.g., eCTD leaf title: SmithJA 2002 Impurities). 

3.4.3 Datasets

The FDA technical specifications document Study Data Technical Conformance Guide

provides details on the submission of datasets and related files (e.g., data definition file, 
Contains Nonbinding Recommendations

15

program files).16 Datasets should be provided only in modules 3 – 5 of the eCTD.

Updated datasets should “replace” the old dataset. Do not use “append” when updating 

datasets.

3.5 Module 5 – Clinical 

The organization of Module 5 is the same for all applications and related submissions. 

The documents for Module 5 should be placed in the m5 folder, and the subject matter 

for each document should be specific for the lowest level of the hierarchy outlined in 

the FDA technical specification Comprehensive Table of Contents Headings and 

Hierarchy. The headings for study reports should also be specific for the lowest level 

of the hierarchy. Each document should be provided as an individual PDF file. Please 

refer to the Study Data Technical Conformance Guide for additional requirements.

3.5.1 Tabular Listing of All Clinical Studies

The tabular listing of all clinical studies should be provided as a single PDF file in 

section 5.2 of the eCTD. For ease of review, hyperlinks to the referenced studies in m5

should be provided. A study tagging file (STF) is not necessary for the tabular listing 

of clinical studies. 

3.5.2 Study Reports

When providing a study report, you should include the STF described in the associated 

ICH M2 technical specification The eCTD Backbone File Specification for Study 

Tagging Files and required by the eCTD Guidance.17 Individual study documents 

should be referenced in an STF using the appropriate STF ‘file-tag’ describing the 

document’s contents. In the case where no other file tag is appropriate, you may use 

“study report body”.

Typically, study reports should be provided according to the FDA guidance for 

industry ICH E3 Structure and Content of Clinical Study Reports. The individual 

documents that should be included in a study report are listed in the FDA technical 

specification Comprehensive Table of Contents Headings and Hierarchy. 

Study reports should be provided as separate documents. Additional information (e.g., 

audit information or a publication based on the study) should be provided as a separate 

file, rather than replacing the entire study report.

In cases when a legacy report has already been prepared as a single electronic 

document, you should provide the entire study report as a single document, not 

including the case report forms (CRFs) and individual data listings. The file tag 

“legacy-clinical-study-report” should be used for the study report.

16 Study Data Resources page is located at: 

https://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm. 17 Available via eCTD Submissions Standards catalog. The catalog is located on the FDA eCTD website 

(https://www.fda.gov/ectd) 
Contains Nonbinding Recommendations

16

Human Factors submissions should be in Module 5.3.5.4 Other Study Reports and 

Related Information and should include the appropriate human factors file tag (e.g., 

HF-validation protocol, HF-validation report, HF-validation other) to describe the 

document’s contents. 

3.5.3 Case Report Forms (CRFs)

An individual subject’s complete CRF should be provided as a single PDF file. If a 

paper CRF was used in the clinical trial, the electronic CRF should be a scanned image 

of the paper CRF including all original entries with all modifications, addenda, 

corrections, comments, annotations, and any extemporaneous additions. If electronic 

data capture was used in the clinical trial, a PDF-generated form or other PDF 

representation of the information (e.g., subject profile) should be submitted. Each CRF 

should be included with its corresponding clinical study report and should be 

referenced by the report’s STF, individually tagged as ‘case-report-forms.’ FDA does 

not use the eCTD heading 5.3.7 for CRFs, therefore do not place files under this 

heading.

The subject’s unique identifier should be used as the title of the document and the file 

name. These names are used to assist reviewers in finding the CRF for an individual

subject. Each CRF must have bookmarks as part of the comprehensive table of 

contents required under 21 CFR 314.50(b). Each CRF domain and study visit should 

be bookmarked to assist reviewers in their review of CRFs. For addenda and 

corrections, avoid confusion by making a hypertext link from the amended item to the 

corrected page or addendum. Bookmarks for these items should be displayed at the 

bottom of the hierarchy.

3.5.4 Periodic Safety Reports

Periodic safety reports18 consist of two parts: a descriptive portion and the individual 

case safety reports (ICSR). Only the descriptive portion of the periodic report may be 

submitted to the eCTD.

The descriptive portion of the report may be sent as either the periodic adverse (drug) 

experience report (PADER) or the ICH-E2C periodic safety update report (PSUR) 

(allowed with approved waiver). Either format may be submitted to the eCTD in

section 5.3.6 as an individual PDF file without an STF. Include the reporting period in 

the document’s leaf title. 

Do not submit ICSR E2B formatted XML files in eCTD. 

3.5.5 IND Safety Reports

Each individual IND safety report with its associated study should be provided in 

section 5.3 of the eCTD. Each safety report should be referenced in the study’s STF 

using the ‘safety-report’ file tag, with "Safety Report" in the eCTD leaf title along with 

"initial" or "follow-up", depending on the content of the individual safety report. Each 

IND safety report should be submitted as “new” without replacing any previously 

submitted information. Leaf titles that clearly relate to the individual cases should be 

18 Periodic adverse drug experience reports or periodic adverse experience reports, as described in 21 CFR 

314.80 and 600.80, respectively.
Contains Nonbinding Recommendations

17

used. For additional details on providing IND safety reports, refer to the FDA 

guidance for industry Sponsor Responsibilities—Safety Reporting Requirements and 

Safety Assessment for IND and Bioavailability/Bioequivalence Studies. 

3.5.6 Literature References

Provide each literature reference as an individual PDF file (not referenced by a STF) in 

section 5.4 of the eCTD, as per eCTD Specifications 3.2.2. The file names and eCTD 

leaf titles should be short and meaningful (e.g., eCTD leaf title: SmithJA 2002

Impurities).

3.5.7 Datasets

The FDA technical specifications document Study Data Technical Conformance Guide

provides details on the submission of datasets and related files (e.g., data definition file, 

program files).19 Datasets should be provided only in modules 3 – 5 of the eCTD.

Updated datasets should “replace” the old dataset. Do not use “append” when updating 

datasets.

3.5.8 aECG Waveform

aECG file(s) should be submitted under the relevant study by the application owner. 

The aECG file(s) should be referenced within the study’s STF (study tagging file) and 

use a file-tag of “ecg”. For further details, see the aECG FAQ20.

In general, aECG file(s) should only be submitted for QT studies supporting ICH E14 

QT assessment. These aECG files are typically reviewed by CDER Interdisciplinary 

Review Team for Cardiac Safety Studies (formerly QT-IRT). Please visit IRT’s web

page for more information about cardiac safety studies and contact the review division 

to confirm aECG files(s) are needed prior to submission.

19 Available at https://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm. 20 Available at https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/interdisciplinaryreview-team-cardiac-safety-studies-formerly-qt-irt
Contains Nonbinding Recommendations

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4. Issues and Solutions

4.1 Issue: Combining Multiple 3.2.S or 3.2.P Sections With Similar Metadata

This issue is caused by leafs being submitted with incorrect metadata (‘name’, 

‘manufacturer’, and/or ‘dosage form’ which are not an exact match to what was 

submitted previously).

To resolve:

• Use the eCTD “delete” operator to delete all the leaf IDs that were referenced in 

the section to be deleted. Deleting all leafs will remove the entire section from 

our review tool.

• Reference the files using new leaf IDs, ensuring that the ‘name’, ‘manufacturer’, 

and/or ‘dosage form’ metadata is an exact match to the section where you want 

to place the leafs. 

This issue is also caused when multiple 3.2.P sections were submitted for multiple 

strengths of the same drug product.

In general, when a single application for multiple strengths can be submitted, 

information for each of the product presentations and manufacturing schemes should 

be combined and presented together in one Drug Product section, with information for 

each of the product presentations and manufacturing schemes provided in the 

Appendices and Regional Information sections, as warranted. See FDA guidance for 

industry, M4: The CTD – Quality, Questions and Answers/Location Issues for more 

information.

4.2 Issue: Clinical Study Report Submitted in Incorrect Section

To resolve:

Use the eCTD “delete” operator to delete all the leaf IDs that were referenced in the STF 

under the wrong heading element. This action deletes the STF itself from our review 

tool.

• Create a new STF referencing all the same files, but use new leaf IDs.

• Submit the updated STF in a new submission sequence.

• Resubmission of files should not be necessary. Create the new leafs with file 

references to the documents submitted in the original sequence.

4.3 Issue: Not Applicable (N/A) or Unassigned Folders in Module 4 or 5

This issue is caused by leafs submitted without an STF in a section that requires STFs.

To resolve:

• Use the eCTD “delete” operator to delete all the leaf IDs that were not 

referenced by an STF.

• Create a new STF referencing all the same files, but use new leaf IDs.

• Submit the STF in a new submission sequence.

• Resubmission of files should not be necessary. Create the new leafs with file 
Contains Nonbinding Recommendations

19

references to the documents submitted in the original sequence.

4.4 Issue: Multiple Similar STF Structures Displaying in Module 4 or 5

This issue is caused by an updated STF being submitted with incorrect metadata (studyid and study title not an exact match).

To resolve:

• Use the eCTD “delete” operator to delete all the leaf IDs that were referenced in 

the STF with incorrect study-id or study title metadata. This action deletes the 

STF itself from our review tool.

• Create a new STF referencing all the same files, but use new leaf IDs. Ensure 

that the study-id and study title are an exact match to the original STF.

• Submit the updated STF in a new submission sequence.

• Resubmission of files should not be necessary. Create the new leafs with file 

references to the documents submitted in the original sequence.
Contains Nonbinding Recommendations

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5. Combination Products

Combination Products21

Generally, drug or biological product information for combination drug and device 

product information and related engineering and manufacturing information should be 

located in the same eCTD sections that would provide similar information for the drug 

or biological product alone. This particularly applies to device constituent parts that 

also serve as the drug container closure system. For example, the M3 quality module 

should contain information on such devices constituents in section 3.2.P.7. Supportive 

files for container closure device constituents should be located in section 3.2.R. For 

other types of device constituent parts that do not have a logical location within 3.2.P, 

the information should be placed in 3.2.R. For example, quality data for a free standing 

laser would be in 3.2.R. Quality information on the combination product as a whole 

(not the separate constituent parts) should be located in 3.2.P with appropriate 

hyperlinks to 3.2.R. The following recommendations should be followed by sponsors 

and applicants for combination products:22

1. General format comments

a. Use of eCTD headings: Adhere to eCTD headings as defined in the 

FDA technical specification Comprehensive Table of Contents 

Headings and Hierarchy. 

b. Node extensions: Do not use node extensions to create new elements. 

Although this is described in the ICH eCTD specification, and may be 

acceptable in some regions, it is not acceptable in any submissions to 

FDA. 

c. Leaf titles: As there are no-sub elements permitted under 3.2.R, when 

placing combination product files in this section, prefix the leaf title 

with “DEVICE” as this will help the reviewer differentiate between 

combination and other categories of files. 

2. Module 1, Section 1.2

To facilitate the review, a reviewer’s guide should be provided in section 1.2 

cover letters. The reviewer’s guide is separate from the cover letter and 

referenced after the cover letter. It should provide a high-level overview (with 

reference links) of the submission’s content and should list the location of 

information in the eCTD. 23 For example, it should identify where drug, device, 

and combination product information is located. Additionally, the reviewers 

21 As set forth in 21 CFR part 3, a combination product is a product composed of any combination of a 

drug, device, or biological product.

22 FDA recognizes the breadth of combination product designs. The information in this guide is to promote 

consistency and facilitate timely review. The agency recommends that applicants, who wish to provide

data in a different location, should contact the review division for discussion. Applicants that wish to 

continue to use a location based on legacy submissions for the same application may continue to use that 

location.

23 If referencing previously submitted information not in the eCTD format, see section 3.1.3 of this guide-

“Cross Referencing Previously Submitted Information that is not in eCTD Format”
Contains Nonbinding Recommendations

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guide should identify the location of information that cannot be further 

identified within the electronic format. This particularly applies to the 

following:

• Files that are not currently listed as numerical items in ICH and FDA 

specifications and guidance documents (e.g., Comprehensive Table of 

Contents Headings and Hierarchy24). For example, the reviewer’s 

guide should provide reference links to each file in section 3.2.R. 

• Sections which are repeated through the use of different XML attributes 

(e.g. <m3-2-p-drug-product product-name = “Albuterol”>; <m3-2-pdrug-product product-name = “Dry Powder Inhaler”>)

3. Module 1.1. Forms

Form 356h should identify all facilities involved in the manufacture and testing of 

the combination product (drug, device, drug-device combination). Also see item 

4.a below for additional information in Section 3.2.P.3 Manufacture

4. Module 3

a. Section 3.2.P.3 Manufacture 

Combination product manufacturing applies to the entire combination product 

(e.g., drug –device combination) in accordance with 21 CFR Part 4. 25 In Section 

3.2.P.3 include applicable device information pertaining to manufacturing or 

assembly of the finished combination product as a whole. As applicable, this 

section may hyperlink to unique device constituent manufacturing information in 

3.2.R.

i. Section 3.2.P.3.1 Manufacturer(s)

• For each facility identify the type of manufacturing and testing 

activities that occur

• For each facility that is subject to 21 CFR part 4, identity whether it 

follows the combination product streamlined manufacturing approach 

and identify the base set of regulations (i.e., 21 CFR 211 or 820).

• Provide a detailed list of all manufacturing facilities; what activities 

occur at the site (e.g., assembly, filling, sterilization, testing, other); 

what constituents are at the site (e.g., drug only, device only, both drug 

and device). For the facilities that have both the drug and device, 

identify which combination product operating system is used at the site.

ii. Section 3.2.P.3.2 Batch Formula (nm, df)

24Available via eCTD Submissions Standards catalog. The catalog is located on the FDA eCTD website 

(https://www.fda.gov/ectd) 25 21 CFR Part 4 “Current Good Manufacturing Practice Requirements for Combination Products” is 

accessible at https://www.federalregister.gov/articles/2013/01/22/2013-01068/current-good-manufacturingpractice-requirements-for-combination-products
Contains Nonbinding Recommendations

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Use this section to describe only the drug components and 

composition.

iii. Section 3.2.P.3.3 Description of Manufacturing Process and Process 

Controls (nm, df)

This section would contain any submitted general 

descriptions/summaries. It may cross reference to section 3.2.R to 

support the manufacturing process.

• Management Controls

• Design Control, General

• Purchasing Controls

• Corrective Action

b. Section 3.2.P.5 Drug Product

Section 3.2.P.5, should usually be an element of a repeated section, as 

appropriate. The first 3.2.P Drug Product section would be for the drug product 

(e.g., <m3-2-p-drug-product product-name = “midazolam injection”>. The 

second 3.2.P Drug Product section might be for the final combination product lot 

release specifications that include the specification requirements for the device 

constituent (e.g. <m3-2-p-drug-product product-name = “midazolam pre-filled 

syringe”>). These specifications should rely on the device design transfer data 

(see design control information) and should link to the supporting eCTD data 

section; e.g., in section 3.2.R.

c. Section 3.2.P.7 Container Closure System

Continue to use this section for devices that serve as primary or secondary 

container closure. Please refer to FDA guidance on Container Closure for 

additional information.26 This section may link to section 3.2.R as appropriate for 

device constituent testing. 

d. Section 3.2.R Regional Information

This section may be used for device engineering design documentation and 

narrative explanations that are not otherwise provided in Section 3.2.P.7. 

Examples of the information include the following:

A. Design Input Requirements

B. Design Output Specifications (e.g., device description, drawings, 

specifications, bill of materials, etc.)

C. Design Verification Plan/Summary Report and supporting data (e.g., 

software, electromechanical conformance, bench testing, biocompatibility)

26 Guidance to Industry: Container Closure Systems for Packaging Human Drugs and Biologics; 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/container-closure-systemspackaging-human-drugs-and-biologics
Contains Nonbinding Recommendations

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D. Design Validation Plan/Summary Report and supporting data (e.g., 

performance testing, narrative discussion of the applicability of data 

provided in Module 5). 

E. Risk Management File

F. Traceability Matrix

Note: Section 3.2 R does not provide for subordinate sections. Every file is listed 

under a common heading. Leaf titles should be clear, concise and indicative of 

the document's content. Please refer to section 2.4 of this guide for additional 

information on leaf titles. In this section, for device related files, each leaf title 

should be prefixed with “DEVICE:”

5. Module 5

Human Factors submissions for the combination product should be located in 

eCTD section 5.3.5.4 Other Study Reports with links from appropriate Module 

3 files, and should include the appropriate human factors file tag (e.g., HFvalidation protocol, HF-validation report, HF-validation other) to describe the 

document’s contents. Additionally, you may cross reference from Module 5 to 

Module 3 as applicable. 
Contains Nonbinding Recommendations

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References

The following are technical specifications documents incorporated by reference into the 

guidance for industry Providing Regulatory Submissions in Electronic Format — Certain 

Human Pharmaceutical Product Applications and Related Submissions Using the eCTD 

Specifications. These documents are located on the FDA eCTD website at: 

https://www.fda.gov/ectd.

1. ICH technical specification, Electronic Common Technical Document Specification 

v3.2.2 (also accessible at https://www.ich.org/page/ich-electronic-common-technicaldocument-ectd-v322-specification-and-related-files)

2. ICH M2 technical specification, The eCTD Backbone File Specification for Study 

Tagging Files

3. FDA technical specification, eCTD Backbone Files Specification for Module 1

4. FDA guidance for industry, M4 Organization of the Common Technical Document 

for the Registration of Pharmaceuticals for Human Use

5. ICH M2 technical specification, eCTD IWG Question and Answer and Specification 

Change Request Document

6. FDA technical specification, FDA eCTD Table of Contents Headings and Hierarchy

7. FDA technical specification, Specifications for File Format Types Using eCTD 

Specifications

8. FDA technical specification, FDA Portable Document Format (PDF) Specifications

9. FDA guidance for industry, Integrated Summaries of Effectiveness and Safety: 

Location Within the Common Technical Document

10. FDA technical specification, Transmission Specifications, Specification for 

Transmitting Electronic Submissions Using eCTD Specifications

11. FDA technical specification, eCTD Validation Specifications, Specifications for 

eCTD Validation Criteria
Contains Nonbinding Recommendations

25

Related References

1. FDA guidance for industry, Providing Regulatory Submissions in Electronic Format 

— Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act 

(accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm under Electronic Submissions)

2. FDA guidance for industry, Providing Regulatory Submissions in Electronic Format 

— Standardized Study Data (accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm under Electronic Submissions)

3. FDA guidance for industry, Formal Meetings Between the FDA and Sponsors or 

Applicants of PDUFA Products (accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm)

4. FDA guidance for industry, Formal Meetings Between the FDA and Sponsors or 

Applicants of BsUFA Products (accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm)

5. FDA guidance for industry, Providing Regulatory Submissions in Electronic Format 

— Receipt Dates (accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm under Electronic Submissions)

6. FDA guidance for industry, M4: The CTD – Quality, Questions and 

Answers/Location Issues (accessible at

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm under International Conference on Harmonisation - Joint Safety/Efficacy 

(Multidisciplinary))

7. FDA guidance for industry, Sponsor Responsibilities—Safety Reporting Requirements 

and Safety Assessment for IND and Bioavailability/Bioequivalence Studies

(accessible at 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/d

efault.htm)