Providing Regulatory Submissions 

in Electronic Format — Certain 

Human Pharmaceutical Product 

Applications and Related 

Submissions Using the eCTD 

Specifications

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)

February 2020

Electronic Submissions

Revision 7
Providing Regulatory Submissions 

in Electronic Format — Certain 

Human Pharmaceutical Product 

Applications and Related 

Submissions Using the eCTD 

Specifications 

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) 

February 2020

Electronic Submissions

Revision 7
RELATED DOCUMENTS

Technical specifications associated with this guidance are provided as separate documents 

and are updated periodically. Documents cited within this guidance are provided at the 

end of this document.

For a complete listing of all documents and supportive files needed to submit electronically, 

refer to the eCTD web page at 

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Elect

ronicSubmissions/ucm153574.htm.

REVISION HISTORY

DATE SUMMARY OF REVISIONS

April 2017

Update to Guidance

Section I. Introduction

• Added paragraph describing rationale for changing timetable for required

master file submissions in eCTD from 24 months to 36 months

Section III.B. Timetable for Implementation of Electronic Submission Requirements

• Updated section to reflect that the requirement for master files to be filed 

electronically takes effect 36 months after May 5, 2015

• Updated example of timetable to reflect actual timetable for the implementation 

of the electronic submissions requirement

April 2018

Update to Guidance

Section I. Introduction

• Added paragraph describing rationale for extending timetable for Type III drug 

master file submissions in eCTD for an additional 12 months

Section III.A. Types of Submissions That Must Adhere to the Electronic Submission 

Requirement Described in This Guidance

• Revised paragraph to reflect change in nomenclature of “biologic product files 

(BPFs)” to “other master files relevant to a biological product”

Section III.B. Timetable for Implementation of Electronic Submission Requirements

• Updated section to reflect that the requirement for Type III drug master files to 

be filed electronically takes place 48 months after May 5, 2015

• Updated example of timetable to reflect actual timetable for the implementation 

of the electronic submissions requirement
January 2019

Section I. Introduction 

• Added paragraph describing rationale for extending timetable for Type III drug 

master file submissions in eCTD for an additional 12 months 

Section III.B. Timetable for Implementation of Electronic Submission Requirements 

• Updated section to reflect that the requirement for Type III drug master files to 

be filed electronically takes place 60 months after May 5, 2015 

• Updated example of timetable to reflect actual timetable for the implementation 

of the electronic submissions requirement

July 2019

Update to Guidance

Section I. Introduction

• Added paragraph describing the addition of exemptions and waivers from 

complying with eCTD requirements

Section III.C. Types of Submissions That Are Exempted From the eCTD Requirement 

Described in This Guidance

• Updated section to include exemption for Type III drug master files

Section III.D. Types of Submissions That May Qualify for a Long-Term Waiver From 

the eCTD Requirement Described in This Guidance

• Added section to include waiver criteria for certain PET drug INDs, NDAs, 

ANDAs, and BLAs, and waiver criteria for certain Type II DMFs

Section III.E. Types of Submissions That May Qualify for a Short-Term Waiver From 

the eCTD Requirement Described in This Guidance

• Added section to include the criteria to qualify for a waiver and the instructions 

on how to submit a request for a short-term waiver
TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 2

III. REQUIREMENT TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE3

A. Types of Submissions That Must Adhere to the Electronic Submission Requirement 

Described in This Guidance...................................................................................................................3

B. Timetable for Implementation of Electronic Submission Requirements..................................5

C. Types of Submissions Exempted From the eCTD Requirement Described in This Guidance6

D. Certain Positron Emission Tomography (PET) Drugs and Type II DMF Submissions That 

May Qualify for a Waiver From the eCTD Requirement Described in This Guidance ..................6

1. Certain Positron Emission Tomography (PET) Drug Submissions.................................................7

2. Certain Type II DMF Submissions ..................................................................................................8

3. Where to Submit Waiver Requests...................................................................................................8

4. FDA Response to Waiver Requests..................................................................................................9

E. Types of Submissions That May Qualify for a Short-Term Waiver From the eCTD 

Requirement Described in This Guidance ...........................................................................................9

1. Content of Waiver Requests...........................................................................................................10

2. Where to Submit Waiver Requests.................................................................................................10

3. FDA Response to Waiver Requests................................................................................................11

F. The eCTD Specifications.............................................................................................................11

G. Pre-Submission Considerations..................................................................................................12

H. Submission Structure: Granularity, Files, and Folders ..........................................................12

I. File Formats and Versions ..........................................................................................................13

J. Document Life Cycle....................................................................................................................13

K. Summary of Clinical Efficacy and Summary of Clinical Safety..............................................13

L. Datasets and Study Information.................................................................................................13

M. Transmitting Electronic Submissions........................................................................................14

N. FDA Forms...................................................................................................................................14

O. Restrictions on Submission of Paper Copies.............................................................................14

P. Receipt Date..................................................................................................................................14

IV. TECHNICAL SPECIFICATION DOCUMENTS REFERENCED IN THIS 

GUIDANCE................................................................................................................................. 16

V. RELATED REFERENCES ........................................................................................... 17
1

Providing Regulatory Submissions in Electronic Format — Certain 

Human Pharmaceutical Product1 Applications and Related 

Submissions Using the eCTD Specifications

Guidance for Industry2

I. INTRODUCTION

Under section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), at least 

24 months after the issuance of a final guidance document in which the Food and Drug 

Administration (FDA or Agency) has specified the electronic format for submitting submission 

types to the Agency, such content must be submitted electronically and in the format specified by 

FDA.3,4 This guidance describes how sponsors and applicants must organize the content that

they submit to the Agency electronically for all submission types under section 745A(a) of the 

FD&C Act. This guidance also references several technical specification documents5 and the 

Electronic Common Technical Document Conformance (eCTD) Guide, which provide additional 

details regarding the organization of content for electronic submissions.6

 1 The term human pharmaceutical product, as used in this guidance, includes any product intended for human use 

that meets the definition of drug and does not also meet the definition of device under the Federal Food, Drug, and 

Cosmetic Act (FD&C Act), including both drugs approved under the FD&C Act and biological products approved 

under the Public Health Service Act (PHS Act). Similarly, for the purposes of this guidance, unless otherwise 

specified, the term drug refers to human prescription drugs, including those that are licensed as biological products 

(biologics).

2 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for 

Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA).

3

 See 21 U.S.C 379k–1.

4 For additional information on how FDA interprets and intends to implement the electronic submission 

requirements of section 745A(a) of the FD&C Act, please see 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). 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.

5 For instance, to reflect the evolving nature of the technology and the experience of those using this technology, the 

electronic common technical document (eCTD) technical specifications are being provided as separate documents in 

connection with this guidance. These associated specifications will be updated periodically. For the most recent 

versions of related technical specifications (CDER and CBER), check the eCTD web page at

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/u

cm153574.htm.

6 For the most recent version of the eCTD Technical Conformance Guide, check the eCTD Resources web page at 

https://www.fda.gov/drugs/developmentapprovalprocess/formssubmissionrequirements/electronicsubmissions/ucm5

35180.htm. 
2

This guidance implements the electronic submission requirements of section 745A(a) of the 

FD&C Act for the electronic format of the content submitted in new drug applications (NDAs), 

abbreviated new drug applications (ANDAs), certain biologics license applications (BLAs), and 

certain investigational new drug applications (INDs) to the Center for Drug Evaluation and 

Research (CDER) or the Center for Biologics Evaluation and Research (CBER). See section 

III.A of this guidance for more information regarding required submission types. Submissions 

that are not submitted electronically and electronic submissions that are not in a format that FDA 

can process, review, and archive will not be filed or received unless they have an exemption or 

waiver from the electronic submission requirements.

The revised guidance published on May 5, 2015, provided a timetable of 24 months after 

issuance of the final guidance for the initial implementation of the electronic submission 

requirement for NDAs, ANDAs, BLAs, and master files (May 5, 2017) and 36 months for 

commercial INDs (May 5, 2018). The timetable indicated that NDAs, BLAs, ANDAs, and 

master files were to be submitted electronically in eCTD format starting on May 5, 2017 (May 5, 

2018, for commercial INDs). Subsequently, in April 2017, in response to industry comments 

and internal review, FDA extended the implementation date for drug master files (DMFs) to 

36 months (to May 5, 2018) (Revision 4) and in April 2018, FDA extended the implementation 

date for Type III DMFs to 48 months (May 5, 2019) (Revision 5). After publication of Revision 

5, FDA determined that many of the concerns expressed in industry comments and confirmed by 

internal review remained. Therefore, the Agency issued a revision to this guidance to further 

extend the implementation date for Type III DMFs until May 5, 2020 (Revision 6).

This revision to the guidance (Revision 7) modifies previous versions by including exemptions 

for Type III DMFs (see section III.C). In addition, this guidance has been updated to include the 

criteria identifying those types of submissions that may qualify for a long-term waiver (see 

section III.D) or a short-term waiver (see section III.E) from eCTD submission requirements and

also includes instructions on how to submit a waiver request. 

II. BACKGROUND

In section 745A(a) of the FD&C Act, Congress granted explicit authorization to FDA to 

implement the statutory electronic submission requirements in guidance and required that FDA 

“shall” issue such guidance. Accordingly, as indicated by the words must or required, this 

document is not subject to the usual restrictions in FDA’s good guidance practice (GGP) 

regulations, such as the requirement that guidances not establish legally enforceable 

responsibilities (see 21 CFR 10.115(d); see also 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)).

To comply with the GGP regulations and make sure that regulated entities and the public 

understand that guidance documents are nonbinding, FDA guidances ordinarily contain standard 

language explaining that guidance documents should be viewed only as recommendations unless 

specific regulatory or statutory requirements are cited. FDA is not including this standard 
3

language in this guidance because it is not an accurate description of all the effects of this 

guidance. Insofar as this document specifies the format for electronic submissions or provides 

“criteria for waivers of and exemptions” from the requirements of section 745A(a) of the FD&C 

Act, it will have binding effect. 

III. REQUIREMENT TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE

As of May 5, 2017, sponsors and applicants must submit the content for which an electronic 

format for submission is specified in this guidance in such electronic format unless the 

submission is exempted or waived. In other words, such submissions must be consistent with the 

requirements set forth below.

A. Types of Submissions That Must Adhere to the Electronic Submission 

Requirement Described in This Guidance

Section 745A(a) of the FD&C Act applies to submissions under section 505(b), (i), or (j) of the 

FD&C Act and under section 351(a) or (k) of the Public Health Service (PHS) Act. These 

include the following submission types:

• Certain investigational new drug applications (INDs)7,8

• New drug applications (NDAs)

• Abbreviated new drug applications (ANDAs)

• Certain biologics license applications (BLAs)9,10

 7 This guidance is not applicable to investigational new drug applications (INDs) for devices that are regulated by 

CBER as biological products under section 351 of the PHS Act and that also require the submission of an IND 

before the submission of a biologics license application (BLA). Although a discussion of which devices CBER 

regulates as biological products is outside the scope of this guidance, as a general matter, this category of INDs 

would include investigational devices that are used to screen blood donations for certain transfusion-transmissible 

infections and to test human cells, tissues, or cellular or tissue-based products to make a donor-eligibility 

determination. These submissions are subject to the requirements under section 745A(b) of the FD&C Act. See the 

guidance for industry and FDA staff eCopy Program for Medical Device Submissions (December 2015), which 

implements the electronic copy provisions of section 745A(b) for medical device submissions to FDA.

8 This guidance is not applicable to noncommercial INDs.

9 This guidance is not applicable to those devices that are regulated by CBER as biological products under section 

351 of the PHS Act, including those that do not require the submission of an IND before the submission of a BLA. 

Although a discussion of which devices CBER regulates as biological products under section 351 of the PHS Act is 

outside the scope of this guidance, as a general matter, this category would include devices that are used to screen 

blood donations for certain transfusion-transmissible infections and reagents used in determining donor/recipient 

compatibility in transfusion medicine. These submissions are subject to the requirements under section 745A(b) of 

the FD&C Act. See the guidance for industry and FDA staff eCopy Program for Medical Device Submissions.

10 Specifically, this guidance is not applicable to submissions for blood and blood components, including Source 

Plasma.
4

Section 745A(a) also applies to all subsequent submissions, including amendments, supplements, 

and reports, to the submission types identified above.11,12

FDA considers master files to be submissions to an NDA, ANDA, BLA, or IND, and therefore to 

fall within the scope of requirements set forth in section 745A(a). These include new DMFs (21 

CFR 314.420) and other master files relevant to a biological product (21 CFR 601.51)13 and any 

amendments to or annual reports on previously submitted DMFs or other master files relevant to 

a biological product. This guidance also applies to submissions for drug/device combination 

products filed pursuant to section 505 of the FD&C Act or subsection (a) or (k) of section 351 of 

the PHS Act.

A submission that is not in the electronic format(s) described in this guidance will not be filed or 

received unless it has an exemption or waiver for the electronic submission requirements (see 

sections III.C., III.D., and III.E.) with respect to that submission.

Under section 745A(a)(3) of the FD&C Act, the electronic submission requirements do not apply 

to submissions described in section 561 of the FD&C Act (e.g., expanded access INDs and 

protocols for individual patients, including for emergency use; expanded access INDs and 

protocols for intermediate-sized patient populations; and expanded access treatment INDs and 

protocols). FDA will continue to accept submissions under section 561 in alternative formats

(e.g., PDF files following the common technical document (CTD) organization).

14

 

11 Although certain postmarketing safety report submissions fall within the scope of section 745A(a) of the FD&C 

Act, FDA has separate regulations that require postmarketing safety reports to be submitted in electronic format (see 

21 CFR 310.305, 314.80, 314.98. 600.80, and 600.81 and section 760 of the FD&C Act) and has issued related nonbinding guidance on these postmarketing safety reports. Accordingly, FDA has not issued guidance under section 

745A with respect to electronic format for postmarketing safety reports. For recommendations with respect to 

submissions related to postmarketing safety reports under §§ 310.305, 314.80, 314.98. 600.80, 600.81, or section 

760 of the FD&C Act, see the draft guidance for industry Providing Submissions in Electronic Format —

Postmarketing Safety Reports (June 2014). When finalized, this guidance will represent the FDA’s current thinking 

on this topic. FDA may consider, at a future date, whether to include information pertaining to submission of 

postmarketing safety reports in electronic format in guidance under section 745A(a) of the FD&C Act. 

12 For further information about IND safety reports, see 21 CFR 312.32 and the guidance for industry Safety 

Reporting Requirements for INDs and BA/BE Studies (December 2012). Additional information may also be found 

in the draft guidance for industry Providing Regulatory Submissions in Electronic Format: IND Safety Reports

(October 2019). When finalized, this guidance will represent the FDA’s current thinking on this topic. 

13 For the purposes of this guidance, the term DMF refers to both drug master files and master files relevant to 

biological products.

14 See the ICH guidance for industry M4 Organization of the Common Technical Document for the Registration of 

Pharmaceuticals for Human Use (October 2017). 
5

B. Timetable for Implementation of Electronic Submission Requirements

The requirement to submit NDAs, ANDAs, and BLAs electronically became effective 24 months 

after May 5, 2015 (i.e., May 5, 2017), the original date of finalization of this guidance 

(Revision 3). The requirement for INDs and master files, other than Type III DMFs, to be filed 

electronically became effective 36 months after May 5, 2015 (i.e., May 5, 2018). For all of these 

submission types, if you do not have an exemption or waiver, you must electronically submit any 

amendments, supplements, and reports in eCTD format, even if the original submission was 

submitted to FDA in non-eCTD format before implementation of the electronic submission 

requirements.

The timetable for the initial implementation of the electronic submission requirement is shown in 

italics below. Table 1 summarizes the timetable.

On May 5, 2015, FDA issued the final guidance for industry on Providing Regulatory 

Submissions in Electronic Format — Certain Human Pharmaceutical Product 

Applications and Related Submissions Using the eCTD Specifications. Submission types 

NDA, ANDA, and BLA must be submitted in eCTD format beginning May 5, 2017. IND 

submissions and master files, other than Type III DMFs, must be submitted in eCTD 

format beginning May 5, 2018.

Table 1: Timetable for the Initial Implementation of the Electronic Submission 

Requirement

Submission

Type

Final eCTD Guidance

Posted on FDA 

Website

(yyyy-mm-dd)

Date Requirement

Begins

(yyyy-mm-dd)

NDA

ANDA

BLA

2015-05-05 2017-05-05

Commercial IND 

Master Files Other Than 

Type III DMFs

2015-05-05 2018-05-05

Additional information regarding submissions pertaining to promotional materials made to the 

Office of Prescription Drug Promotion in CDER and to the Advertising and Promotional 

Labeling Branch in CBER is described in a separate guidance. Refer to that guidance for the 

timetable for implementation of those submissions in electronic format.15

 15 See the guidance for industry Providing Regulatory Submissions in Electronic and Non-Electronic Format —

Promotional Labeling and Advertising for Human Prescription Drugs (June 2019). 
6

C. Types of Submissions Exempted From the eCTD Requirement Described in 

This Guidance

Section 745A(a)(2) of the FD&C Act allows FDA to establish exemptions from the electronic 

submission requirements. Accordingly, FDA has exempted the following from the eCTD 

requirements under section 745A(a)(2):

16 

1. All submissions to noncommercial INDs.

17 For the purposes of this guidance, the term 

noncommercial IND refers to an IND for a product that is not intended for commercial 

distribution; this exemption includes research and investigator-sponsored INDs.

2. All Type III DMF submissions.18

Although these specific submissions will be exempt from filing in eCTD format as described in 

this guidance, FDA still encourages applicants to send submissions in an alternative electronic

format (e.g., PDF files following the CTD structure). 

D. Certain Positron Emission Tomography (PET) Drugs and Type II DMF

Submissions That May Qualify for a Waiver From the eCTD Requirement

Described in This Guidance

Section 745A(a)(2) authorizes FDA to establish criteria for waivers from its electronic 

submission requirements. Accordingly, FDA may grant a long-term waiver from the eCTD 

requirements under section 745A(a)(2)19 in the following circumstances:

 

 16 See section III.B of the 745A(a) Implementation Guidance (Providing Regulatory Submissions in Electronic 

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

IND submissions are not required to submit a request for this exemption.

17 Noncommercial IND submissions are not required to submit a request for this exemption. Although INDs 

covered under section 561 of the FD&C Act might be referred to as a type of noncommercial IND, they have been 

statutorily excepted from the scope of section 745A(a). As a result, they need not submit in eCTD format, albeit for 

a different reason than the submissions exempted here. See section III.A of this guidance for information on the 

types of INDs covered under section 561 of the FD&C Act.

18 Type III DMFs are submitted to the Agency to provide information regarding packaging or packaging materials in 

support of NDAs, ANDAs, or BLAs. The DMF web page is accessible at

https://www.fda.gov/drugs/developmentapprovalprocess/formssubmissionrequirements/drugmasterfilesdmfs/default.

htm.

19 See section III.C of the 745A(a) Implementation Guidance.
7

1. Certain Positron Emission Tomography (PET)

20 Drug Submissions

The requirement to comply with the eCTD requirement for certain PET IND, NDA, ANDA, or 

BLA submissions could adversely impact the development and availability of PET drugs. FDA 

may grant a waiver to a PET drug sponsor or applicant intending to submit an IND, NDA, 

ANDA, or BLA if all of the following apply:

(a) The applicant produces PET drugs at a single PET drug facility.

(b) PET drugs are the only FDA-regulated drug products (other than noncommercial drug 

or biologic products) manufactured or produced by the sponsor or applicant.

(c) The sponsor or applicant explains that, because it meets the criteria above, it cannot 

achieve compliance with eCTD requirements.

A waiver request should be sent to FDA before submitting the document(s) for which this 

waiver is claimed,

21 with an explanation regarding why the sponsor or applicant’s 

compliance with the requirement cannot be achieved, including that the sponsor or 

applicant is representing that (a) through (c) above are met22 and a description of the 

proposed alternative submission format23 the sponsor or applicant will be using during the 

duration of the waiver (e.g., PDF files following the CTD structure). 

The information provided in the waiver request may be verified through inspection or through a 

records request in lieu of an inspection. 

 20 PET is a medical imaging method that produces a computerized image (scan) using a unique type of 

radiopharmaceutical. A PET drug is a radioactive drug characterized by spontaneous disintegration of unstable 

nuclei by the emission of positrons and is used for providing dual photon positron emission tomographic diagnostic 

images (21 CFR 212.1). PET drugs are distinct among radiopharmaceuticals because of their unique production 

methods, and many are characterized by their short half-lives (some as short as 20 minutes). Many PET drug 

production facilities are close in proximity to the patients to whom the drugs are administered, and the production of 

the drug is on demand. 

21 Sponsors and applicants should request a pre-assigned application number before submitting a waiver request.

22 See section 745A(a) of FD&C Act and 21 CFR 312.10 and 314.90(a)(1).

23 If submission in eCTD format is not possible, FDA still encourages applicants to send submissions electronically 

in an alternative electronic format (e.g., PDF files following the CTD structure). 
8

2. Certain Type II DMF24 Submissions

Holders of certain Type II DMFs that solely support an application for a PET drug or a 

noncommercial IND application may also qualify for a waiver. FDA recognizes that the holders 

of these Type II DMFs may be distinct from the holder of the application(s) in question. FDA 

may grant a waiver to a holder intending to submit a Type II DMF if the Type II DMF holder

explains that it cannot achieve compliance with eCTD requirements because one of the following 

applies:

(a) The Type II DMF is intended to support an application for a PET drug (i.e., IND, 

NDA, ANDA, or BLA) and contains information regarding radiolabeled drug 

products or production of PET radionuclides, and the Type II DMF holder is an 

academic institution, government (state or federal) entity, or a non-profit25 research 

organization.

OR

(b) The Type II DMF is solely used to support a noncommercial IND application, and the 

Type II DMF holder is an academic institution, government (state or federal) entity, 

or a non-profit research organization.

A waiver request should be sent to FDA before submitting the document(s) for which this 

waiver is claimed,

26 with an explanation regarding why the sponsor or applicant’s 

compliance with the eCTD requirement cannot be achieved (i.e., that the sponsor or 

applicant is representing that (a) or (b) above is met), including a description of the 

proposed alternative submission format27 the sponsor or applicant will be using during the 

duration of the waiver (e.g., PDF files following the CTD structure). 

The information provided on the waiver request may be verified through inspection or through a 

records request in lieu of an inspection. 

3. Where to Submit Waiver Requests

The waiver requests for qualifying PET drugs or Type II DMFs should be submitted in one of 

the following ways:

 24 Type II DMFs are submitted to the Agency to support drug applications to make quality information available for 

Agency evaluation of the quality of active pharmaceutical ingredients and drug products used in investigational 

studies. 

25 For the purposes of this guidance, a non-profit is a charitable organization recognized as tax-exempt under section 

501(c)(3) of the United States Internal Revenue Code of 1986 (Title 26 of the United States Code).

26 Sponsors and applicants should request a pre-assigned application number before submitting a waiver request.

27 See footnote 23. 
9

• CDER: 

- Email to esub@fda.hhs.gov

• CBER 

- Email to esubprep@cber.fda.gov

The waiver request should reference all products that are to be covered by the waiver. The 

waiver request should be clearly titled “LONG-TERM WAIVER REQUEST — eCTD 

REQUIREMENTS” in bold capital letters at the top of the first page of the submission.

4. FDA Response to Waiver Requests

FDA reviews waiver requests on a case-by-case basis. FDA will generally respond to the 

requestor28 in writing, stating whether the waiver is granted or denied and whether the proposed 

alternative submission format is acceptable. Long-term waivers from the requirement to 

submit in eCTD format, if granted, will be valid for five (5) years from the date the waiver 

is granted, will apply only to the requestor, and will not be transferrable to another 

sponsor or applicant. Sponsors or applicants may reapply to recertify their eligibility for this 

waiver up to 6 months before the waiver expiration date, using the same process as described in 

section III.D.3 of this guidance. If the criteria are no longer met at the time of recertification, the 

waiver will not be granted.

If FDA grants a waiver, the requestor should include a statement in the cover letter of each 

subsequent submission(s) indicating that an eCTD submission waiver has been granted by 

FDA, including the dates for the waiver. 

Although these specific submissions may receive waivers from eCTD format requirements as 

described in this guidance, FDA still encourages applicants to send submissions electronically in 

an alternative electronic format (e.g., PDF files following the CTD structure).29 

E. Types of Submissions That May Qualify for a Short-Term Waiver From the 

eCTD Requirement Described in This Guidance

Section 745A(a)(2) of the FD&C Act authorizes the Agency to set forth criteria for waivers from 

the requirements of electronic submissions. FDA will grant short-term waivers from the eCTD 

requirement only in unique and rare circumstances and for a limited duration. Companies 

experiencing technical difficulties with transmission of their electronic submissions to FDA 

should consult FDA for technical assistance rather than submitting a waiver request. FDA may 

 28 To follow up with the company, FDA will generally contact the individual who submitted the waiver request 

unless an alternate contact person is provided.

29 See footnote 23. 
10

grant temporary waivers of the requirement for eCTD submission if one or more of the following 

events or circumstances exist: 

• Extraordinary events or circumstances occur that are beyond the control of the submitter

that justify a waiver, including but not limited to, natural disasters that impact computer 

operations.

• An unplanned long-term internet disruption or other unplanned event occurs that would 

preclude the sponsor from submitting in eCTD format (e.g., malware attacks).

• The sponsor or applicant intends to request a withdrawal of an application that has not yet 

converted to eCTD format.

• The sponsor or applicant submitted a request for withdrawal and has not yet received 

FDA’s acknowledgement of the withdrawal.

1. Content of Waiver Requests

The sponsor or applicant’s request to waive the eCTD electronic format requirement must

include all of the following as supporting documentation to justify the waiver:

30

(a) A description of the circumstances or event — including the anticipated duration

of the circumstance or event — giving rise to the need for a waiver

(b) The requested duration of the waiver

(c) A description of the proposed alternative submission format31 the sponsor or 

applicant will be using for the duration of the waiver

The request should reference all products that are to be covered by the waiver. The waiver 

request should be clearly titled “WAIVER REQUEST — eCTD REQUIREMENTS” in bold 

capital letters at the top of the first page of the submission.

Please submit waiver requests before filing a submission to which the waiver is claimed. 

2. Where to Submit Waiver Requests

Waiver requests for NDAs, BLAs, ANDAs, DMFs, and commercial INDs may be sent to FDA 

through the following means:

 30 See 21 CFR 312.10(a)(3) and 314.90(a)(3).

31 See footnote 23.
11

• CDER

- Email to esub@fda.hhs.gov

• CBER

- Email to esubprep@cber.fda.gov

3. FDA Response to Waiver Requests

FDA reviews waiver requests on a case-by-case basis. FDA will generally respond to the 

requestor32 in writing, stating whether the waiver is granted or denied. If the waiver is granted, 

FDA will also generally include in its response letter a description of the alternate submission 

method(s) the Agency intends to accept and the time frame for the waiver. Waivers of the 

requirement to submit in eCTD format, if granted, will be temporary, will apply only to 

the requestor, and will not be transferrable to another sponsor. If FDA grants a waiver, 

the requestor should include a statement in the cover letter of subsequent submission(s) 

indicating that an eCTD submission waiver has been granted by FDA, including the dates 

for the waiver.

Although these specific submissions may receive waivers from eCTD format requirements as 

described in this guidance, FDA still encourages applicants to send submissions electronically in 

an alternative electronic format (e.g., PDF files following the CTD structure33). 

F. The eCTD Specifications

You must submit electronic submissions using the version of eCTD currently supported by FDA.

The version of eCTD currently supported is specified in the Data Standards Catalog (available at

https://www.fda.gov/media/85137/download) and is further described in the following technical 

specification documents:

• International Council for Harmonisation (ICH) Electronic Common Technical Document 

Specification

• ICH eCTD Backbone File Specification for Study Tagging Files

• FDA eCTD Backbone Files Specification for Module 1

Additional technical specification documents are cited throughout this document. For a

complete listing of required technical supportive files (e.g., style sheets and valid values) that 

you will need to submit in the eCTD format, refer to the eCTD web page at 

 32 To follow up with the company, FDA will generally contact the individual who submitted the waiver request 

unless an alternate contact person is provided.

33 See footnote 23.
12

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Elect

ronicSubmissions/ucm153574.htm.

G. Pre-Submission Considerations

Before making the first electronic submission to an application, you must obtain a pre-assigned 

application number by contacting the appropriate Center. Information regarding how to obtain a 

pre-assigned application number may be found on the eCTD web page at 

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Elect

ronicSubmissions/ucm153574.htm.

H. Submission Structure: Granularity, Files, and Folders

Document granularity, or the level for which the submission content is broken out into separate 

files, must be consistent with the Granularity Document found in the 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 M2 technical specification 

eCTD IWG Question and Answer and Specification Change Request Document.

With a few exceptions, the eCTD specification maps CTD headings to extensible markup 

language (XML) elements.34 The specification indicates that each element (heading) is optional 

and that multiple document references (eCTD leaf elements) can be created under each heading.

You must also follow the FDA eCTD technical specification The Comprehensive Table of 

Contents Headings and Hierarchy for the comprehensive listing of headings and hierarchy and a 

section mapping the headings to their respective regulations.35 Because this is a comprehensive 

listing, not all headings are applicable to all submissions or submission types.

Files pertaining to each module must be placed in the appropriate folder (e.g., m1 – 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 must have specific names.

You must use only letters, numbers, hyphens, or underscores in the folder and file names and not 

blank spaces or special characters. When naming folders and files, the length of the entire path 

must not exceed 150 characters. Empty folders and files must not be included in the submission.

All documents in the electronic submission must be placed in a main submission folder and 

named using a four-digit sequence number (which you must specify) that is unique within the 

 34 For example, in Module 3, lower-level headings subordinate to 3.2.P.2 (e.g., 3.2.P.2.1, 3.2.P.2.1.1) are not 

mapped to an XML element. Consequently, leaf element files relating to, for example, 3.2.P.2.1, 3.2.P.2.1.1, either 

must be submitted as multiple leafs under the parent 3.2.P.2 element (heading) or combined into larger files and 

submitted at the 3.2.P.2 heading level.

35 See https://www.fda.gov/media/76444/download.
13

application. The eCTD backbone file for modules 2 to 5 (index.xml) for the submission must 

be placed in this folder along with the checksum file for the eCTD backbone file (indexmd5.txt).

Numbering for each subsequent submission to the same application is described in the FDA 

technical specification in section III.B of the eCTD Backbone Files Specification for Module 1. 

Sequence numbers are used to differentiate between 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 required to organize files in a submission. These subfolders 

must be placed in the sequence number folder. Empty subfolders must not be included. The util

subfolder is required to organize supporting eCTD technical files in the submission, as described 

in the ICH M2 technical specification Electronic Common Technical Document Specification. 

Other specific folder names that are compliant with the eCTD version 3.2.2 format can be found 

in the same document.

I. File Formats and Versions

Files within an eCTD submission must adhere to the formats and versions specified in the 

associated FDA technical specification Specifications for File Format Types Using eCTD 

Specifications. Portable Document Format (PDF) files submitted must adhere to the FDA 

technical specification Portable Document Format (PDF) Specifications.

J. Document Life Cycle

If a document replaces a document previously submitted with an eCTD backbone file within the 

same application, you must use the eCTD replace operation to indicate this, rather than 

submitting the file as new. You must not indicate that files are new if they are in fact replacing 

files already submitted. If you intend to remove a file, you must use the delete operation. For 

instructions, see the ICH M2 technical specification Electronic Common Technical Document 

Specification.

K. Summary of Clinical Efficacy and Summary of Clinical Safety

When submitting a Summary of Clinical Efficacy and/or a Summary of Clinical Safety, the 

location of these documents within the eCTD must adhere to the guidance for industry Integrated 

Summaries of Effectiveness and Safety: Location Within the Common Technical Document

(April 2009).

L. Datasets and Study Information

Datasets must only be provided in modules 3, 4, or 5 and not in modules 1 or 2. When providing 

study information in either module 4 or 5, you must include the Study Tagging File (STF) 

described in the associated ICH M2 technical specification eCTD Backbone File Specification 
14

for Study Tagging Files (see section III.F of this guidance). Datasets must be referenced in an 

STF using the appropriate STF file-tag describing the document’s contents.

For further information regarding the submission of study data, see the guidance for industry

Providing Regulatory Submissions in Electronic Format — Standardized Study Data (December 

2014).

M. Transmitting Electronic Submissions

The FDA Electronic Submissions Gateway (ESG)36 enables the secure submission of regulatory 

information for review and is our preferred method of transmission. For all submissions that are 

10 gigabytes (GB) or smaller, you must use the FDA ESG.

For submissions that are greater than 10 GB, refer to the FDA technical specification

Transmitting Electronic Submissions Using eCTD Specifications.

N. FDA Forms

Electronic submissions must include only FDA fillable forms (e.g., Form FDA 1571 or Form 

FDA 356h) 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 will not be accepted.

O. Restrictions on Submission of Paper Copies

When submitting in eCTD format, paper copies of the application, including review copies and 

desk copies in paper, must not be submitted. The only exception to this is the submission of 

paper copies of meeting briefing materials, when requested, as described in the guidances for 

industry on formal meetings between the FDA and sponsors or applicants.

37

P. Receipt Date

The receipt date for an electronic submission will be determined only after the submission has 

passed a technical validation check to ensure that it can be opened, processed, and archived. The 

submitter is responsible for monitoring their receipt pathway to determine whether a submission 

has been rejected. Additional information on the validation of electronic submissions is 

available in the FDA technical specification Specifications for eCTD Validation Criteria.

 36 Additional information concerning the FDA ESG is available at 

https://www.fda.gov/industry/electronic-submissions-gateway.

37 See also the following draft guidances: Formal Meetings Between the FDA and Sponsors or Applicants of 

PDUFA Products (December 2017) and Formal Meetings Between the FDA and Sponsors or Applicants of BSUFA 

Products (June 2018). When finalized, these guidances will represent FDA’s current thinking on these topics.
15

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, you should contact the Center electronic submission coordinator at 

esub@fda.hhs.gov for submissions to CDER and at esubprep@fda.hhs.gov for submissions to 

CBER. Specific questions pertaining to the content of applications should be directed to the 

appropriate review division or office.
16

IV. TECHNICAL SPECIFICATION DOCUMENTS REFERENCED IN THIS 

GUIDANCE

The following are technical specification documents referenced in this guidance (see section I). 

Documents are listed in order of first appearance in this guidance.

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.

1. ICH M2 technical specification, Electronic Common Technical Document Specification

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

Change Request Document

5. FDA technical specification, FDA eCTD Comprehensive Table of Contents Headings 

and Hierarchy

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

Specifications

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

8. FDA technical specification, Transmission Specifications, Transmitting Electronic

Submissions Using eCTD Specifications

9. FDA technical specification, eCTD Validation Specifications web page, Specifications 

for eCTD Validation Criteria
17

V. RELATED REFERENCES

The guidance documents referenced below can be accessed via FDA’s guidance web page at

https://www.fda.gov/industry/fda-basics-industry/guidances.

1. 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)

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

— Standardized Study Data (December 2014)

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

Applicants of PDUFA Products (December 2017)

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

Applicants of BSUFA Products (June 2018)

5. FDA draft guidance for industry Providing Submissions in Electronic Format –

Postmarketing Safety Reports (June 2014)

6. FDA guidance for industry Providing Regulatory Submissions in Electronic Format 

— Receipt Dates (February 2014)

7. ICH guidance for industry M4 Organization of the Common Technical Document for 

the Registration of Pharmaceuticals for Human Use (October 2017)

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

Location Within the Common Technical Document (April 2009)

9. FDA guidance for industry Reporting Requirements for INDs and BA/BE Studies

(December 2012).

10. FDA draft guidance for industry Providing Regulatory Submissions in Electronic 

Format: IND Safety Reports (October 2019).

11. FDA draft guidance for industry Providing Regulatory Submissions in Electronic and 

Non-Electronic Format — Promotional Labeling and Advertising for Human 

Prescription Drugs (June 2019).