Providing Regulatory Submissions 
in Alternate Electronic Format 
 
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) 
 
 
 
June 2022 
Electronic Submissions 
Revision 1 
 
40244414fnlrv1.docx   
Providing Regulatory Submissions 
in Alternate Electronic Format 
 
Guidance for Industry 
 
 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
 
and/or 
 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances     
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
June 2022 
Electronic Submissions 
Revision 1
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  HOW TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE ................... 2 
A.  How to Submit in Alternate Electronic Format (without XML backbone) ............................. 2 
B.  FDA Forms ..................................................................................................................................... 4 
C.  Pre-Submission Considerations .................................................................................................... 4 
D.  Submission Structure:  Granularity, Files, and Folders ............................................................ 4 
E.    File Formats and Versions ............................................................................................................ 5 
F.  Datasets and Study Information ................................................................................................... 5 
G.  Transmitting Electronic Submissions .......................................................................................... 5 
H.    Receipt Dates .................................................................................................................................. 5 
IV.  FDA TECHNICAL SPECIFICATION DOCUMENTS REFERENCED IN THIS 
GUIDANCE ................................................................................................................................... 6 
V.  RELATED REFERENCES ............................................................................................. 6 
  Contains Nonbinding Recommendations 
 
Providing Regulatory Submissions in Alternate Electronic Format 
Guidance for Industry1 
 
 
 
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 provides recommendations on an alternate electronic format for submissions 
covered under an exemption from or a waiver of the requirements of section 745A(a) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 379k-1).  These 
recommendations pertain to the format of content contained in new drug applications (NDAs), 
abbreviated new drug applications (ANDAs), certain drug master files (DMFs), certain biologics 
license applications (BLAs), and certain investigational new drug applications (INDs) submitted 
to the Center for Drug Evaluation and Research (CDER) or to the Center for Biologics 
Evaluation and Research (CBER).2   
 
Sponsors and applicants who receive an exemption or a waiver from filing in electronic common 
technical document (eCTD) format under section 745A(a) of the FD&C Act should still provide 
those exempted or waived submissions electronically.  This recommendation is consistent with 
the efforts of Federal Agencies to transition their business processes and recordkeeping to a fully 
electronic environment.3 
 
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, 
 
1 This guidance has been prepared by the Office of Medical Policy in the Center for Drug Evaluation and Research 
in cooperation with the Center for Biologics Evaluation and Research at the Food and Drug Administration.  
 
2 For more information on types of submissions covered under an exemption from or a waiver of the requirements of 
section 745A(a) of the FD&C Act, refer to the guidance for industry Providing Regulatory Submissions in 
Electronic Format  Certain Human Pharmaceutical Product Applications and Related Submissions Using the 
eCTD Specifications (February 2020) available on the FDA eCTD website at https://www.fda.gov/ectd.  We update 
guidances periodically.  For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
 
3 See https://www.archives.gov/records-mgmt/memos/ac22-2019. 
  1  Contains Nonbinding 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.  
 
 
II.  BACKGROUND 
 
In section 745A(a) of the FD&C Act, Congress granted FDA the authority to implement the 
Agencys statutory electronic submission requirements in guidance.  In response to this 
authorization, FDA implemented binding guidance requiring submission of NDAs, BLAs, 
ANDAs, DMFs, and commercial INDs to the Agency in eCTD format.  Recognizing that certain 
types of submissions are exempt from this requirement and that waivers of the requirement may 
be granted on a case-by-case basis, the Agency is issuing this guidance to describe the alternate 
electronic format companies should use for submissions covered under such exemptions and 
waivers. 
 
 
III.  HOW TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE 
 
A.  How to Submit in Alternate Electronic Format (without XML backbone) 
 
Although the alternate electronic format utilizes the same folder structure found in eCTD 
submissions, it does not include XML and other specific files needed for electronic display.  The 
alternate electronic format does not require specialized software.  Commercial off-the-shelf 
software or other methods4 may be used to either build or view the submission; but like eCTD, the 
alternate electronic format should follow the FDA technical specification The Comprehensive 
Table of Contents Headings and Hierarchy.5  For information on file format and versions, see 
section III.E of this guidance. 
   
Main Submission Folder 
 
All documents and data files should be placed in a main folder (top-level) using the application 
type and number (e.g., IND123456) as the folder name.  A table of contents with hyperlinks and 
bookmarks should be provided in numerical order in the sequence folder (e.g., 0001) for ease of 
navigation to all the files contained in the submission.  The alternate electronic format should 
follow the eCTD Technical Conformance Guide (e.g., Section 3.1.2 Cover Letter and Reviewers 
Guide).6 
 
 
4 Sponsors submitting a research IND (also called a noncommercial IND) to CDER may use the Research IND 
Application Builder within the CDER NextGen Portal to build and transmit IND submissions (https://edm.fda.gov). 
 
5 The Comprehensive Table of Contents Headings and Hierarchy may be found in the eCTD Submissions Standards 
document, available on the FDA eCTD website at https://www.fda.gov/ectd. 
 
6 The eCTD Technical Conformance Guide is available on the FDA eCTD website at https://www.fda.gov/ectd. 
  2  Contains Nonbinding Recommendations 
 
Folders 
 
Inside the sequence folder, there should be five or fewer folders, depending on the documents 
being submitted:  m1, m2, m3, m4, and m5.  The documents should be organized and placed in 
their respective modules, folders, or subfolders as displayed in the FDA technical specification The 
Comprehensive Table of Contents Headings and Hierarchy. 
 
 
 
Each item has an assigned module and subfolder where document and data files that belong to 
the item should be placed.  Files pertaining to each module should be placed in the appropriate 
folder (e.g., m1 through m5).  The terms folder and subfolder, as used in this guidance, are 
intended to be synonymous with directory and subdirectory.  The main submission, regional 
administrative folders, and certain subfolders should have specific names.  Table 1 shows the 
organization of modules and their descriptions. 
 
Table 1.  Module and Description Organization 
 
Module  Description 
1  Administrative Information 
2  Summaries 
3  Quality 
4  Nonclinical Information 
5  Clinical Information 
 
Folder Organization 
 
For recommendations on how to organize submission content, refer to the eCTD Technical 
Conformance Guide.7  The majority of information in the eCTD Technical Conformance Guide is 
applicable to eCTD and non-eCTD submissions. 
 
 
7 Ibid. 
  3  Contains Nonbinding Recommendations 
 
B.  FDA Forms  
 
Electronic submissions should include only FDA fillable forms (e.g., 1571, 356h, 2252) and 
electronic signatures to enable automated processing of the submission.  FDA forms are available 
at https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm.  Scanned images of 
FDA forms should not be submitted.8 
 
C.  Pre-Submission Considerations 
 
Before making the first alternate electronic submission, a pre-assigned application number 
should be obtained by contacting CDER or CBER.  For more information on obtaining a pre-
assigned application number, see FDAs eCTD web page at  
https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/submit-using-ectd. 
 
D.  Submission Structure:  Granularity, Files, and Folders 
 
The level at which the submission content is broken out into separate files should be consistent 
with the International Council for Harmonisation (ICH) guidance for industry M4 Organization 
of the Common Technical Document for the Registration of Pharmaceuticals for Human Use 
(October 2017) unless otherwise specified in the ICH guidance for industry M2: eCTD 
Specification Questions & Answers and Change Requests (March 2005). 
 
The FDA technical specification The Comprehensive Table of Contents Headings and Hierarchy 
should be followed for the comprehensive listing of headings and hierarchy and for section 
mapping the headings to their respective regulations.  Given that this technical specification 
includes a comprehensive listing, not all headings are applicable to all submissions or submission 
types. 
 
Letters, numbers, hyphens, and underscores may be used in the folder and file names, but you 
should not use blank spaces or special characters.  When naming folders and files, the length of 
the path should not exceed 150 characters.  Empty folders and files should not be included in the 
submission. 
 
Sequence numbers are used to differentiate submissions within the same application and need 
not correspond to the order in which they are received by FDA.  It is not necessary for sequence 
numbers and IND serial numbers to match for submissions to an IND. 
 
Subfolders within each module are used to organize files in a submission.  These subfolders 
should be placed in the sequence number folder.   
 
 
8 If it is not possible to provide an electronic signature to the form, submitting a signed and scanned copy of the 
fillable form is acceptable.  An unsigned electronic version of the fillable form should be included with such 
submission so the data can be processed by FDA systems. 
 
  4  Contains Nonbinding Recommendations 
 
E.    File Formats and Versions 
 
Files within an alternate electronic submission should adhere to the formats and versions 
specified in the associated FDA technical specification Specifications for File Format Types 
Using eCTD Specifications.  PDF files should adhere to the FDA technical specification Portable 
Document Format (PDF) Specifications. 
 
F.  Datasets and Study Information 
 
Datasets should only be provided in modules 3, 4, or 5, and not in modules 1 or 2. 
 
For further information on the submission of study data, see the guidance for industry Providing 
Regulatory Submissions in Electronic Format  Standardized Study Data (December 2014). 
 
G.  Transmitting Electronic Submissions 
 
The FDA Electronic Submissions Gateway (ESG)9 enables the secure submission of regulatory 
information for review.  For all submissions in alternate electronic format that are 10 gigabytes 
(GB) or smaller, the FDA ESG should be used. 
 
For submissions that are greater than 10 GB, refer to the FDA technical specification 
Transmitting Electronic Submissions using eCTD Specifications. 
 
H.    Receipt Dates 
 
The receipt date for an electronic submission is established tentatively when the submission 
arrives through the ESG and then permanently when the submission is determined to be 
technically acceptable, in that it can be opened, processed, and archived.  FDA will notify 
submitters regarding any technical deficiencies as they are encountered.  However, each 
submitter is responsible for monitoring their receipt pathway to determine whether a submission 
has been rejected.   
 
Additional information on receipt dates for electronic submissions is available in the  
guidance for industry Providing Regulatory Submissions in Electronic Format  Receipt Dates 
(February 2014).   
 
Contact Information 
 
For questions related to providing electronic submissions according to the recommendations in 
this guidance, contact the appropriate electronic submission coordinator: 
 
  CDER submissions:  esub@fda.hhs.gov  
 
 
9 Additional information concerning the FDA ESG is available at https://www.fda.gov/industry/electronic-
submissions-gateway.  
 
  5  Contains Nonbinding Recommendations 
 
  CBER submissions:  esubprep@fda.hhs.gov      
 
Specific questions pertaining to the content of applications should be directed to the appropriate 
review division or office.   
 
 
IV.  FDA TECHNICAL SPECIFICATION DOCUMENTS REFERENCED IN THIS 
GUIDANCE 
 
The following is a list of FDA technical specification documents referenced in this guidance:  
 
1.  The Comprehensive Table of Contents Headings and Hierarchy  
 
2.  eCTD Technical Conformance Guide   
 
3.  Specifications for File Format Types Using eCTD Specifications  
 
4.  Portable Document Format (PDF) Specifications  
 
5.  Transmitting Electronic Submissions Using eCTD Specifications  
 
For a complete listing of the current technical supportive files that you will need in order to 
submit in eCTD format, refer to the eCTD Submission Standards document located on the eCTD 
web page at https://www.fda.gov/ectd. 
 
 
V.  RELATED REFERENCES 
 
The guidance documents referenced below can be accessed via FDAs guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.10 
 
1.  FDA guidance for industry, Providing Regulatory Submissions in Electronic Format  
Certain Human Pharmaceutical Product Applications and Related Submissions Using 
the eCTD Specifications (February 2020) 
 
2.  FDA guidance for industry, Providing Regulatory Submissions in Electronic Format  
Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act 
(December 2014)  
 
3.  FDA guidance for industry, Providing Regulatory Submissions in Electronic Format  
Standardized Study Data (December 2014) 
 
4.  FDA draft guidance for industry, Formal Meetings Between the FDA and Sponsors or 
Applicants of PDUFA Products (December 2017) 
 
 
10 Note:  Draft guidances are not considered FDAs current thinking until finalized. 
  6  Contains Nonbinding Recommendations 
 
5.  FDA draft guidance for industry, Formal Meetings Between the FDA and Sponsors or 
Applicants of BSUFA Products (June 2018) 
 
6.  FDA draft guidance for industry, Providing Submissions in Electronic Format  
Postmarketing Safety Reports (June 2014) 
 
7.  FDA guidance for industry, Providing Regulatory Submissions in Electronic Format  
Receipt Dates (February 2014) 
 
8.  ICH guidance for industry, M2: eCTD Specification Questions & Answers and Change 
Requests (March 2005) 
 
9.  ICH guidance for industry, M4 Organization of the Common Technical Document for 
the Registration of Pharmaceuticals for Human Use (October 2017) 
 
10. FDA guidance for industry, Integrated Summaries of Effectiveness and Safety:  Location 
Within the Common Technical Document (April 2009) 
 
  7