Brief on eCTD Submissions, Framework and Implementation

1. eCTD SUBMISSIONS
1Gautam G. Halder– Regulatory Affairs 6/12/2018

2. 2Gautam G. Halder– Regulatory Affairs 6/12/2018
WHAT IS eCTD?
The Electronic Common Technical Document
(eCTD) is the standard format for submitting
applications, amendments, supplements, and
reports to FDA’s Center for Biologics Evaluation
and Research (CBER) and Center for Drug
Evaluation and Research (CDER).
STANDARD FORMAT FOR SUBMISSIONS

3. 3Gautam G. Halder– Regulatory Affairs 6/12/2018
WHAT IS eCTD?......CONTINUED
An eCTD submission has five modules: region-specific information, summary
documents, quality-related information, nonclinical study reports, and clinical study
reports.

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FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
FDASIA: Food and Drug Administration Safety and Innovation Act (FDASIA)

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How will eSubmissions be Implemented?
FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION

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FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
When will eCTD Format be Required?
36 months for Commercial INDs

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UPDATES
When will eCTD Format be Required?
Starting May 5, 2018
Ø New MFs and any submissions to existing MFs (e.g.,
amendments, annual reports, letters of authorization
(LOAs)) must be submitted using eCTD.
Ø All submissions must be submitted electronically, even if the
remainder of the MF is on paper.
Ø MF submissions that are not submitted in eCTD format, will
not be filed or received.
Ø The current requirements and supported versions can be
found in the FDA Data Standards Catalog at
www.fda.gov/eStudyResources.

8. 8Gautam G. Halder– Regulatory Affairs 6/12/2018
What Submission Types are Applicable?
FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
*Commercial IND applications (for products that are intended to be distributed
commercially)

9. 9Gautam G. Halder– Regulatory Affairs 6/12/2018
Electronic submission standards will be optional but encouraged for the following
categories:
Ø Noncommercial INDs, such as investigator-sponsored INDs and expanded-access
INDs
Ø Submissions for blood and blood components, including source plasma
Ø Submissions for promotional materials for human prescription drug
What Submission Types are Applicable?
EXEMPTION

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FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
What are the eCTD Specifications?

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What are the eCTD Specifications?
CURRENT VERSIONS AND UPDATES
Ø Submit electronic submissions using
the version of eCTD currently
supported by FDA.
Ø For a listing of Specifications,
Supportive Files, M1 versions 1.3 and
2.3 documents related to eCTD,
please refer to eCTD Submission
Standards (XLS - 57KB) or eCTD
Submission Standards (PDF - 91KB).

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FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
What eCTD Formats will be Required?

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What eCTD Formats will be Required?
Ø Electronic submissions must use the version of eCTD currently supported by FDA,
which is specified in the FDA Data Standards Catalog on the Study Data Standards
Resources page.
Ø Updates to the standard will be announced on the FDA website and published in the
Federal Register.
Ø The notices will include the date on which the new versions will go into effect. For
notices, please see eCTD Important Notices.
CURRENT VERSIONS AND UPDATES

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FRAMEWORK FOR REQUIRED ELECTRONIC SUBMISSION
How to Submit eCTD Submissions?

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How to Submit eCTD Submissions?
CURRENT VERSIONS AND UPDATES
Please refer to eCTD Submission Standards (XLS -
57KB) or eCTD Submission Standards (PDF -
91KB).

16. 16Gautam G. Halder– Regulatory Affairs 6/12/2018
Ø Before making the first electronic submission to an application, you must obtain a
pre-assigned application number by contacting the appropriate Center.
Ø All electronic submissions must have an application number
Ø Information regarding how to obtain a pre-assigned application number may be
found on FDA’s eCTD web page at
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequire
ments/ElectronicSubmissions/ucm114027.htm
PRE-SUBMISSION CONSIDERATIONS
Pre-assigned application number
Requesting a Pre-Assigned Application number
1. Apply for a secure email with the FDA by contacting secureemail@fda.hhs.gov. If
using a US Agent to request the number, please be sure that the agent has
established a secure e-mail.
2. Send one email per application number request to
cderappnumrequest@fda.hhs.gov.
Please note that at this time the Electronic Submission Gateway (ESG) cannot
accept requests for pre-assigned numbers.
3. A pre-assigned number will be issued within 3 business days.

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Resubmission of Material
Ø There is NO requirement to resubmit anything that has already been submitted in
paper
Ø If you choose to resubmit your entire DMF upon conversion to eCTD, that is
acceptable but it is NOT required.
SUBMISSIONS

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Conversion of Paper DMFs to Electronic
Ø If the existing number is 4-digits, e.g. 1234, the DMF holder should pad left with
zeroes to convert to a 6-digit format, e.g. 001234.
Ø Each section should be complete and contain up-to-date information.
Ø DMFs in non-CTD paper format must be converted to CTD format before
submission in eCTD.
Ø Any changes in the technical content of the DMF as a result of the conversion to
CTD format, e.g. addition of new information, should be specified in the cover letter
of the submission.
Ø The numbering of the submissions should start with 0001.
SUBMISSIONS
Ø When converting from paper to electronic, the
holder may submit an amendment containing all
sections specified in the CTD format that are
applicable to the material covered by the DMF.
Ø An existing DMF number may be used when
converting a paper DMF to electronic format.

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Paper to eCTD Examples (v2.01 DTD)
When transitioning from paper to eCTD and holder is utilizing us-regional.xml v2.01
DTD, the most common scenarios are below:
1. First eCTD submission is an amendment to the DMF
• In this case, use a submission type of original-application
Subsequent amendments, including letters of authorization, submitted in eCTD
should use a submission type of amendment
2. First eCTD submission is an annual report
• In this case, use a submission type of annual-report
SUBMISSIONS
DTD: Document type definition
TIP!
FDA prefers eCTD submissions start with sequence 0001

20. 20Gautam G. Halder– Regulatory Affairs 6/12/2018
Paper to eCTD Examples (v3.3 DTD)
When transitioning from paper to eCTD and holder is utilizing us-regional.xml v3.3 DTD,
the most common scenarios are below:
1. First eCTD submission is an amendment to the DMF
• In this case, use a submission type of original-application and submission
subtype of application.
• Use eCTD sequence number = 0001 and Submission ID = 0001
Subsequent amendments, including letters of authorization, submitted in eCTD
should use a submission type of original application and submission subtype of
amendment.
Use next available eCTD sequence number and Submission ID = 0001
(Submission ID for the first eCTD submission to the Original application)
2. First eCTD submission is an annual report
• In this case, use a submission type of annual-report and submission subtype of
report. Use eCTD sequence number = 0001 and Submission ID = 0001.
SUBMISSIONS
DTD: Document type definition
TIP!
FDA prefers eCTD submissions start with sequence 0001

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Electronic Submissions Gateway (ESG)
TRANSMITTING ELECTRONIC SUBMISSIONS
What is Electronic
Submissions Gateway
(ESG)?
Ø The FDA Electronic
Submissions
Gateway (ESG) is
the central
transmission point
for sending
information
electronically to
FDA.
Ø The ESG does not
open or review
submissions.
Ø It receives submissions, acknowledges receipt, routes them to the proper FDA
center or office, and notifies that center or office of delivery.

22. 22Gautam G. Halder– Regulatory Affairs 6/12/2018
Electronic Submissions Gateway (ESG)
TRANSMITTING ELECTRONIC SUBMISSIONS
Submission types
Ø The FDA ESG supports the receipt of guidance-compliant electronic regulatory
submissions to the Center for Biologics Evaluation and Research (CBER) and the
Center for Drug Evaluation and Research (CDER).
Ø The FDA ESG also supports the receipt of reports and attachments for many other
FDA offices and centers. FDA is continually expanding the list of electronic
regulatory submissions that can be received by the ESG.
Submission requirements
Ø As of May 5, 2017, many submissions to CBER and CDER are required to use the
Electronic Common Technical Document (eCTD) format. (For commercial
Investigational New Drugs [INDs] and Master Files, the requirement takes effect on
May 5, 2018.)
Ø Submissions that fall under the eCTD requirement and are 10 GB or less in size
must be submitted via the FDA ESG as of the applicable date. For more information
on these requirements, see www.fda.gov/ectd.

23. 23Gautam G. Halder– Regulatory Affairs 6/12/2018
Electronic Submissions Gateway (ESG)
TRANSMITTING ELECTRONIC SUBMISSIONS
Submission options
There are two methods for submitting to the ESG
1. AS2 Gateway-to-Gateway Connection
Ø Generally used by sponsors that have a high volume of submissions
Ø Allows automated submissions
Ø Requires AS2-compliant software and technical expertise
2. WebTrader
Ø A regular desktop computer can be used for submissions
Ø User can send only one submission at a time
Ø Requires installation of a Java applet but minimal technical expertise

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Electronic Submissions Gateway (ESG)
TRANSMITTING ELECTRONIC SUBMISSIONS
Registration process
Ø Registering to use the FDA ESG involves a
sequence of steps that are to be conducted for
all submitters and types of submissions.
Ø It is best to start well in advance of the time
when you plan to make a submission.
Ø The process includes a testing phase designed
to ensure that the FDA ESG can successfully
receive your electronic submission and that the
electronic submission is prepared according to
published guidelines.
Ø The testing phase is done through the FDA
ESG test system. Once the submitter’s test
submission has passed the testing phase, an
account will be set up allowing submissions to
be sent through the FDA ESG production
system.

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Electronic Submissions Gateway (ESG)
TRANSMITTING ELECTRONIC SUBMISSIONS
Getting started
Ø The first step to submitting electronically through ESG is to request a test account.
Refer to the FDA ESG User Guide, available at www.fda.gov/esg, for information on
how to submit the registration request.
Ø Setting up an ESG account is a multi-step process and should be started well
before you intend to make your first electronic submission.

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MUST DO
See the Guidance for a *complete* list of the “musts”
Ø Must submit electronic submissions using the eCTD version
currently supported by FDA.
§ The version of eCTD currently supported is specified in
the Data Standards Catalog
Ø Must obtain a pre-assigned application number by contacting
the appropriate Center.
§ How? Go to www.fda.gov/ectd
Ø Must follow the FDA eCTD technical specification Table of
Contents Headings and Hierarchy.
§ Find it in the eCTD Submissions Standards catalog

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Find these specifications and more in the eCTD Submissions
Standards catalog
Ø Must adhere to the formats and versions specified in the FDA
Specifications for File Format Types Using eCTD
Specifications.
Ø Must adhere to the FDA Portable Document Format (PDF)
Specifications.
Ø Must use the eCTD replace operation rather than submitting
the file as new if a document replaces a document previously
submitted…
MUST DO

28. 28Gautam G. Halder– Regulatory Affairs 6/12/2018
Ø Must include only FDA fillable forms (e.g., User Fee Form
3794) and electronic signatures to enable automated
processing of the submission…Scanned images of FDA forms
will not be accepted.
Ø Must not submit paper copies of the application, including
review & desk copies when submitting in eCTD format.
Ø Must use the FDA Electronic Submission Gateway for
submissions 10 GB or smaller.
MUST DO

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Must use the FDA Electronic Submission Gateway for submissions 10 GB or
smaller.
See Transmission
Specification
(www.fda.gov/ectd) for
details
Ø If you are not currently an ESG submitter, set up an account now; process can take
several weeks
Ø Most submitters use the “WebTrader Hosted Solution”
Ø There is no cost for an ESG account, but you must obtain a Digital Certificate for
each person in your organization who will be sending files through the ESG
Ø See the ESG website for complete instructions, http://www.fda.gov/esg
MUST DO

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PDF Table of Contents and Bookmarks
Ø Should be the same
Ø For documents 5 pages or longer
Ø Up to 4 levels deep in hierarchy
TIPS FOR DMF SUBMISSION SUCCESS

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BAD – Bookmarks and TOC do not match.
TOC does not contain hyperlinks
TIPS FOR DMF SUBMISSION SUCCESS

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GOOD!
TIPS FOR DMF SUBMISSION SUCCESS

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Orientation
TIPS FOR DMF SUBMISSION SUCCESS

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Orientation
Any documents provided in the submission should be in the correct orientation
TIPS FOR DMF SUBMISSION SUCCESS

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ESG Tips (Electronic Submissions Gateway)
Ø Submissions of 10 GB or less must use the Electronic Submission Gateway (ESG).
Ø Get an account early
• Account activation process contains many steps including submission of a
CDER compliant test submission and passing validation. This may take
multiple attempts and can take weeks.
• Instructions are located at: www.fda.gov/esg
• There is no cost for an ESG account, but you must obtain a digital certificate for
each person in your organization who will be sending files through the ESG.
Ø When transmitting to CDER, choose “CDER” as the center and “eCTD” as the
submission type
Ø When transmitting to CBER, choose “CBER” as the center and “DMF” as the
submission type
Ø Questions related to the Gateway should be directed to:
ESGHELPDESK@fda.hhs.gov
TIPS FOR DMF SUBMISSION SUCCESS

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QUOTE OF THE DAY

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