Providing Regulatory Submissions in Electronic Format: IND Safety Reports Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Providing Regulatory
Submissions in
Electronic Format:
IND Safety Reports
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)
Oncology Center of Excellence (OCE)
April 2024
Electronic Submissions

Providing Regulatory
Submissions in
Electronic Format:
IND Safety Reports
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)
Oncology Center of Excellence (OCE)
April 2024
Electronic Submissions

RELATED DOCUMENTS
Technical specifications associated with this guidance are provided as separate documents and
are updated periodically.
For a complete listing of all documents and supportive files needed to submit investigational new
drug application safety reports to FDA’s Adverse Event Reporting System (FAERS), refer to the
FAERS Electronic Submissions web page at https://www.fda.gov/drugs/fda-adverse-event-
reporting-system-faers/fda-adverse-event-reporting-system-faers-electronic-submissions.

TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 3
III. 	SCOPE OF THIS GUIDANCE ....................................................................................... 3
A. 	Types of Submissions That Will Be Required to Comply With the Electronic Submission
Requirement Described in This Guidance ................................................................................... 3
B. 	Types of Submissions for Which the Electronic Submission Requirement Described in This
Guidance Does Not Apply ............................................................................................................. 4
C. 	Types of Submissions That Are Exempted From the Electronic Submission Requirement
Described in This Guidance .......................................................................................................... 4
IV. 	REQUIREMENT TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE5
A. 	Timetable for Implementation of Electronic Submission Requirements.................................. 5
B. 	Specifications for Submission of IND Safety Reports to FAERS .............................................. 5
C. 	Presubmission Considerations ...................................................................................................... 6
D. 	Waiver Requests ............................................................................................................................ 6
1. Content of Waiver Requests ............................................................................................................. 6
2. Where to Submit Waiver Requests ................................................................................................... 6
3. FDA Response to Waiver Requests .................................................................................................. 7

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Providing Regulatory Submissions in Electronic Format:
IND Safety Reports
Guidance for Industry1
I. 	INTRODUCTION
This guidance describes the electronic format sponsors will be required to use when they
electronically submit to the Food and Drug Administration (FDA or Agency) investigational new
drug application (IND) safety reports for serious and unexpected suspected adverse reactions that
are required under 21 CFR 312.32(c)(1)(i). FDA is establishing the electronic format
requirements described in this guidance under section 745A(a) of the Federal Food, Drug, and
Cosmetic Act (FD&C Act).2 When the requirements of this guidance are in effect, this guidance
will supersede the effective version of the guidance for industry Providing Regulatory
Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and
Related Submissions Using the eCTD Specifications (eCTD guidance) as applicable to the
electronic submission of IND safety reports required under 21 CFR 312.32(c)(1)(i) that are
within the scope of this guidance (see section III., Scope of This Guidance). This guidance will
not replace any requirements in the eCTD guidance other than those relating to the electronic
submission of IND safety reports required under 21 CFR 312.32(c)(1)(i) that are within the
scope of this guidance. This guidance also references several technical specification documents
that provide additional details about the format for electronic submission of IND safety reports to the
FDA Adverse Event Reporting System (FAERS) .3
This guidance implements the electronic submission requirements of section 745A(a) of the
FD&C Act for the electronic format of the content submitted for IND safety reports that are
required under 21 CFR 312.32(c)(1)(i) for serious and unexpected suspected adverse reactions.
This guidance applies to IND safety reports that are submitted to the Center for Drug Evaluation
and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). This
guidance changes the electronic submission requirements for this category of IND safety reports
by requiring sponsors to submit the IND safety reports to FAERS in accordance with this
guidance. This requirement will be effective 24 months after the publication of the notice of
1 This guidance has been prepared by 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 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) (745A(a) Implementation guidance). 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 the technical specifications document FDA Regional Implementation Guide for E2B(R3) Electronic
Transmission of Individual Case Safety Reports for Drug and Biological Products (August 2022) and the Electronic
Submission of IND Safety Reports: Technical Conformance Guide (April 2022), available on the FAERS Electronic
Submissions web page at https://www.fda.gov/drugs/fda-adverse-event-reporting-system-faers/fda-adverse-event-
reporting-system-faers-electronic-submissions.

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availability of this guidance in the Federal Register (April 1, 2026). Until the requirements in
this guidance become effective, the most recent effective version of the eCTD guidance will
continue to apply to sponsors electronically submitting IND safety reports for serious and
unexpected suspected adverse reactions.4 Before the effective date of the requirements outlined
in this guidance, FDA will accept IND safety reports to FAERS as part of a voluntary
submission program. During the voluntary submission program, if sponsors choose to submit
IND safety reports to FAERS, they should no longer submit those IND safety reports in eCTD
format. Please see the FAERS Electronic Submissions web page5 for more information on the
voluntary submission process.
Once the requirement is effective, sponsors of INDs subject to this guidance are required to
submit IND safety reports electronically in the format specified in this guidance unless the
sponsor is exempted from the electronic submission requirements (see section III. C., Types of
Submissions That Are Exempted From the Electronic Submission Requirement Described in
This Guidance) or a waiver is obtained (see section IV. D., Waiver Requests).
In section 745A(a) of the FD&C Act, Congress granted explicit statutory authorization to FDA
to specify in guidance the format for the electronic submissions required under that section.
Accordingly, to the extent that this document provides such requirements under section 745A, as
indicated by the use of the words must or required, this document is not subject to the usual
restrictions in section 701(h) of the FD&C Act, FDA’s good guidance practice regulations that
guidances not establish legally enforceable responsibilities (see 21 CFR 10.115(d); see also the
745A(a) Implementation guidance).
To comply with the good guidance practice regulations and make sure that regulated entities and
the public understand that guidances are nonbinding, FDA guidances ordinarily contain standard
language explaining that guidances should be viewed only as recommendations unless specific
regulatory or statutory requirements are cited. FDA is not including this standard language in
this guidance because it is not an accurate description of all of 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 24 months after the publication of this guidance in the Federal Register.
4 For further information about IND safety reports, see 21 CFR 312.32, the guidance for industry and investigators
Safety Reporting Requirements for INDs and BA/BE Studies (December 2012), and the draft guidance for industry
Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for IND and
Bioavailability/Bioequivalence Studies (June 2021). When final, this guidance will represent the FDA’s current
thinking on this topic. These guidances do not cover electronic submissions requirements. 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 The FAERS Electronic Submissions web page is found at https://www.fda.gov/drugs/fda-adverse-event-reporting-
system-faers/fda-adverse-event-reporting-system-faers-electronic-submissions.

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II. 	BACKGROUND
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 Act, including certain
INDs. Section 745A(a) of the FD&C Act also applies to all subsequent submissions, including
amendments, supplements, and reports to the submission types identified. FDA considers IND
safety reports to fall within the scope of requirements set forth in section 745A(a) of the FD&C
Act.
A sponsor of a clinical trial conducted under an IND must report serious and unexpected
suspected adverse reactions to FDA in an IND safety report within 7 or 15 days depending on the
severity of the event (21 CFR 312.32).4 These reports have traditionally been submitted to FDA
on MedWatch Form FDA 3500A or on a Council for International Organizations of Medical
Sciences I Form or other narrative forms. Submission of this important safety information to
FAERS as structured data elements will improve FDA’s ability to review and track these
potential safety signals that occur during the conduct of clinical trials and will provide sponsors
with a reporting format that is consistent with International Council for Harmonisation (ICH)
guidelines and reporting requirements to other regulatory agencies.
The IND safety reporting requirements under 21 CFR 312.32 apply to bioavailability (BA) and
bioequivalence (BE) studies that are conducted under an IND. However, BA and BE studies that
meet the conditions for exemption under 21 CFR 320.31 are not conducted under an IND and are
not subject to the IND safety reporting requirements. Safety reporting requirements under 21
CFR 320.31(d)(3) apply to persons conducting BA or BE studies that are exempt from the IND
requirements.
III. 	SCOPE OF THIS GUIDANCE
A. 	Types of Submissions That Will Be Required to Comply With the Electronic
Submission Requirement Described in This Guidance
This guidance applies only to IND safety reports for serious and unexpected suspected adverse
reactions required under 21 CFR 312.32(c), which includes both 7- and 15-day reporting
requirements depending on the severity of the event (see 21 CFR 312.32(c)(1)(i), (c)(2)). Under
21 CFR 312.32(c)(1)(i), sponsors must report any suspected adverse reaction that is both serious
and unexpected if there is evidence to suggest a causal relationship between the drug and the
adverse event, such as in the following circumstances:
• 	A single occurrence of an adverse event that is uncommon and known to be strongly
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson
syndrome) (21 CFR 312.32(c)(1)(i)(A))
• 	One or more occurrences of an adverse event that is not commonly associated with drug
exposure but is otherwise uncommon in the population exposed to the drug (e.g., tendon
rupture) (21 CFR 312.32(c)(1)(i)(B))

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• 	An aggregate analysis of specific adverse events observed in a clinical trial (e.g., known
consequences of the underlying disease or condition under investigation, other adverse
events that commonly occur in the study population independent of drug therapy) that
indicates those events occur more frequently in the drug treatment group than in a
concurrent or historical control group (21 CFR 312.32(c)(1)(i)(C))
B. 	Types of Submissions for Which the Electronic Submission Requirement
Described in This Guidance Does Not Apply
This guidance does not apply to IND safety reports for anything other than serious and
unexpected suspected adverse reactions covered by 21 CFR 312.32(c)(1)(i) and 21 CFR
312.32(c)(2).
Below are examples of IND safety reports for which the requirements of this guidance do not
apply:6
− 	Findings from other studies, as required under 21 CFR 312.32(c)(1)(ii)
− 	Findings from animal or in vitro testing, as required under 21 CFR 312.32(c)(1)(iii)
− 	Increased rate of occurrence of serious suspected adverse reactions, as required under 21
CFR 312.32(c)(1)(iv)
This guidance also does not apply to IND safety reports for devices that are regulated by CBER
as biological products under section 351 of the Public Health Service Act and that require the
submission of an IND before the submission of a biologics license application.7
C. 	Types of Submissions That Are Exempted From the Electronic Submission
Requirement Described in This Guidance
Section 745A(a) of the FD&C Act allows FDA to establish exemptions from the electronic
submission requirements. Accordingly, FDA has exempted all submissions regarding
noncommercial INDs from the requirements under section 745A(a) of the FD&C Act.8 For
6 For information on the electronic format requirements for the types of IND safety reporting required under 21 CFR
312.32(c)(1)(ii)-(iv), sponsors should consult the eCTD guidance and the Electronic Submission of IND Safety
Reports: Technical Conformance Guide.
7 Although a discussion of which devices CBER regulates as biological products is outside the scope of this
guidance, in general, this category of INDs would include investigational devices that are used to screen blood
donors for certain transfusion-transmissible diseases 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 (April 2020), which implements the electronic copy provisions of section 745A(b) of the FD&C Act for
medical device submissions to FDA.
8 See the 745A(a) Implementation guidance, section III. B.

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purposes of the section 745A(a) exemption, the term noncommercial IND refers to an IND for a
product that is not intended for commercial distribution and includes investigator-sponsored
INDs and expanded access INDs (e.g., emergency use INDs and treatment INDs).9 Although
noncommercial INDs (and IND safety reports associated with them) are exempt from the
requirements of section 745A(a) of the FD&C Act, FDA encourages the submission of IND
safety reports from sponsors of noncommercial INDs using the format described in this
guidance.
IV. 	REQUIREMENT TO SUBMIT ELECTRONICALLY UNDER THIS GUIDANCE
The following section sets forth the requirements for electronic submission of IND safety reports
that are within the scope of this guidance.
A. 	Timetable for Implementation of Electronic Submission Requirements
The requirement to submit IND safety reports as described in this guidance will become effective
24 months after the publication of this guidance in the Federal Register (April 1, 2026). FDA
will accept IND safety report submissions as described in this guidance before the date that the
requirement is in effect as noted in section I., Introduction.
B. 	Specifications for Submission of IND Safety Reports to FAERS
Sponsors must submit IND safety reports to FAERS using either the Electronic Submission
Gateway (ESG) or the Safety Reporting Portal (SRP). For sponsors using the ESG, consult the
FDA Data Standards Catalog10 for information about the ICH E2B data standard currently
supported by FDA.
For additional information about submitting IND safety reports to FAERS, please consult the
following technical specification documents:11
• 	Electronic Submission of IND Safety Reports: Technical Conformance Guide
• 	FDA Regional Implementation Guide for E2B(R3) Electronic Transmission of Individual
Case Safety Reports for Drug and Biological Products
Instructions for submitting IND safety reports to FAERS as individual case safety reports can be
found on the FAERS Electronic Submissions web page.12
9 See the 745A(a) Implementation guidance, section III. B.
10 The FDA Data Standards Catalog is available on the Study Data Resources web page at
https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources.
11 Available on the FAERS Electronic Submissions web page at https://www.fda.gov/drugs/fda-adverse-event-
reporting-system-faers/fda-adverse-event-reporting-system-faers-electronic-submissions.
12 Available on the FAERS Electronic Submissions web page at https://www.fda.gov/drugs/fda-adverse-event-
reporting-system-faers/fda-adverse-event-reporting-system-faers-electronic-submissions.

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C. 	Presubmission Considerations
Before submitting an IND safety report to FAERS for the first time, whether through the ESG or
SRP, the sponsor should create an account with FDA if one has not been previously established.
To create an account, the sponsor should notify the FAERS electronic submission coordinator at
faersesub@fda.hhs.gov of the intent to submit. The FAERS coordinator will help the sponsor
create an account, ensure that all steps have been completed for successful submission, and
provide instructions for optional test submissions. It is not necessary to contact the FAERS
coordinator before submitting subsequent IND safety reports in electronic format.
D. 	Waiver Requests
Section 745A(a)(2) of the FD&C Act allows FDA to establish criteria for waivers from the
electronic submission requirements. The Agency anticipates that temporary waivers will be
needed only in rare circumstances. FDA may grant temporary waivers of the requirement for
submission of certain IND safety reports in FAERS, as described in this guidance, if one or more
of the following events or circumstances exist:13
• 	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 FAERS (e.g., malware attacks)
1. 	Content of Waiver Requests
The sponsor should make a request in writing to waive the requirement to submit IND safety
reports to FAERS. Include the IND number for which the request is being made, the reason for
the request, and information justifying the waiver.14 The waiver request also should include a
proposed end date for the waiver and the proposed alternative reporting method, such as
submission on physical media.
2. 	Where to Submit Waiver Requests
Waiver requests for drug and biological products conducted under an IND may be sent through
the following means:
• 	CDER: By email to ESUB@fda.hhs.gov
• 	CBER: By email to ESUBPREP@fda.hhs.gov
13 See 21 CFR 312.10.
14 See 21 CFR 312.10.

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3. 	FDA Response to Waiver Requests
FDA reviews waiver requests on a case-by-case basis. FDA will generally respond to the
requestor15 in writing, stating whether the waiver is granted or denied. If the waiver is granted,
FDA will also generally include in the 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
requirements to submit to FAERS, if granted, will be temporary, will apply only to the requestor,
and will not be transferrable to another sponsor.
15 To follow up with the company, FDA will generally contact the individual who submitted the waiver request
unless an alternate contact person is provided.