Providing Submissions 
in Electronic Format
Postmarketing 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) 
 
 
April 2022 
Electronic Submissions 
 
   
Providing Submissions 
in Electronic Format
Postmarketing 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) 
 
 
April 2022 
Electronic Submissions 
 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
I.  INTRODUCTION ...................................................................................................... 1 
II.  BACKGROUND ........................................................................................................ 3 
III.  ICSR SUBMISSIONS ................................................................................................ 4 
A.  General Information ..................................................................................................... 4 
B.  Options for Electronic Submission of ICSRs: Electronic Submissions Gateway or Safety 
Reporting Portal .................................................................................................................. 5 
C.  Create an Account Before Submitting Electronically for the First Time ............................ 6 
D.  Unique Case Identification Numbers for ICSRs .............................................................. 6 
E.  Submitting Labeling and Labels for Unapproved Products .............................................. 7 
F.  Single Submission Versus Batched Submissions of ICSRs ................................................ 7 
G.  Submitting ICSR Attachments ....................................................................................... 7 
IV.  NOTIFICATION OF RECEIPT OF SUBMISSIONS BY FDA ................................ 7 
A.  ESG Message Delivery Notices and FAERS Acknowledgements ....................................... 7 
B.  SRP Acknowledgment ................................................................................................... 8 
V.  CONTINGENCIES WHEN THE ESG, FAERS, OR SRP IS TEMPORARILY 
UNAVAILABLE ................................................................................................................... 9 
A.  Contingencies When Submitting Through the ESG ......................................................... 9 
B.  Contingencies When Submitting Through the SRP.......................................................... 9 
C.  Receipt Dates................................................................................................................ 9 
D.  Physical Media as a Backup Method .............................................................................10 
VI.  DESCRIPTIVE INFORMATION IN PERIODIC SAFETY REPORTS ................ 10 
VII.  WAIVER REQUESTS ............................................................................................. 10 
A.  Content of Waiver Requests..........................................................................................11 
B.  Where to Submit Waiver Requests ................................................................................11 
C.  FDA Response to Waiver Requests................................................................................12 
 
   
  Contains Nonbinding Recommendations 
 
The technical specification associated with this guidance is provided in a separate document and 
is updated periodically.  To ensure that you have the most recent version of the technical 
specifications document, check the FAERS Electronic Submissions web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseD
rugEffects/ucm115894.htm. 
 
  Contains Nonbinding Recommendations 
Providing Submissions in Electronic FormatPostmarketing Safety 
Reports 
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 is one in a series of guidance documents intended to assist industry when making 
certain regulatory submissions in electronic format to FDAs Center for Drug Evaluation and 
Research (CDER) and the Center for Biologics Evaluation and Research (CBER).  This guidance 
provides general information on the electronic submission of postmarketing safety reports under 
the following provisions: 
 
  21 CFR 314.80 and 314.98 (regarding products with approved new drug applications 
(NDAs) and abbreviated new drug applications (ANDAs), respectively, including 
combination products or drug constituent parts with approved NDAs or ANDAs2 
 
  21 CFR 600.80 (regarding products with approved biologics license applications (BLAs), 
including combination products or biological product constituent parts with approved 
BLAs)3 
 
  21 CFR part 4, subpart B (requiring additional reports for combination products with 
approved NDAs, ANDAs, or BLAs)4  
 
  21 CFR 310.305 (regarding prescription drug products marketed for human use without 
approved NDAs or ANDAs, including prescription drug products that are compounded 
 
1 This guidance has been prepared by the Office of Business Informatics and the Office of Surveillance and 
Epidemiology in the Center for Drug Evaluation and Research (CDER) in cooperation with the Center for Biologics 
Evaluation and Research (CBER) and FDAs Office of Combination Products.  
2 See also Postmarketing Safety Reporting for Combination Products: Guidance for Industry and FDA Staff (July 
2019).  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 Id. 
4 Id. 
  1  Contains Nonbinding Recommendations 
by facilities registered as outsourcing facilities under section 503B of the Federal Food, 
Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 353b))5 
 
  21 CFR 329.100 and section 760 of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 379aa) (regarding nonprescription drug products marketed for human use 
without approved NDAs or ANDAs)  
 
However, this guidance does not apply to the following: 
 
  Vaccines6 
 
  Whole blood or blood components7 
 
  Combination products with a drug or biological product constituent part marketed under a 
device application8 
 
  Lot distribution reports9  
 
  Human cells, tissues, and cellular tissue-based products (HCT/Ps) regulated solely under 
section 361 of the Public Health Service Act10 
 
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.   
 
5 See the guidance for industry Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the 
Federal Food, Drug, and Cosmetic Act (October 2015). 
6 Electronic submissions of postmarketing safety reports for vaccines is addressed in the guidance for industry 
Providing Submissions in Electronic FormatPostmarketing Safety Reports for Vaccines (August 2015).  
7 Blood collection and transfusion facilities report fatalities related to blood collection or transfusion under 21 CFR 
606.170(b).  Information on submitting these reports is available at https://www.fda.gov/vaccines-blood-
biologics/report-problem-center-biologics-evaluation-research/transfusiondonation-fatalities.  
8 As specified in 21 CFR 4.104, combination product applicants are required to submit Fifteen-day reports (as 
described in 21 CFR 314.80 or 21 CFR 600.80) in accordance with 21 CFR 803.12(a) if the combination product 
received marketing authorization under a device application.  For additional reporting requirements for combination 
products marketed under a device application, see 21 CFR part 4, subpart B.  For guidance on reporting 
requirements for combination products, see Postmarketing Safety Reporting for Combination Products: Guidance 
for Industry and FDA Staff (July 2019). 
9 Lot distribution reports are not considered postmarketing safety reports; however, under FDAs final rule, 
Postmarketing Safety Reports for Human Drug and Biological Products; Electronic Submission Requirements (79 
FR 33072, June 10, 2014), such reports are required to be submitted to FDA in electronic format that the Agency 
can process, review, and archive (see 21 CFR 600.81(b)(1)).  Information on submitting lot distribution reports is 
available at https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Post-
MarketActivities/LotReleases/ucm061966.htm and in the guidance for industry Electronic Submission of Lot 
Distribution Reports (March 2015). 
10 Submission of adverse reaction reports for HCT/Ps that are regulated solely under section 361 of the Public 
Health Services Act is required under 21 CFR 1271.350.  Although FDAs final rule on electronic safety reporting 
does not require that such reports be submitted electronically, FDA encourages electronic submission of these 
reports, and this guidance may provide useful information to those interested in submitting HCT/P adverse reaction 
reports electronically. 
  2  Contains Nonbinding Recommendations 
FDA guidance documents, including this guidance, should be viewed only as 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 
 
On June 10, 2014, FDA published a final rule to amend its postmarketing safety reporting 
regulations for human drug and biological products to require that persons subject to mandatory 
reporting requirements submit safety reports in an electronic format that the Agency can process, 
review, and archive.11  The final rule also established 21 CFR 329.100 to address electronic 
submission of postmarketing safety reports required by section 760 of the FD&C Act.  The 
compliance date for these requirements was September 8, 2015.12, 13  At the time FDA published 
the final rule it also made available a revised draft guidance for industry entitled Providing 
Submissions in Electronic FormatPostmarketing Safety Reports.14  This guidance finalizes the 
revised draft guidance and contains recommendations on submitting postmarketing safety reports 
electronically in accordance with the final rule. 
 
This guidance is intended for any party with postmarketing safety reporting responsibilities 
under the provisions that are within the scope of this guidance as described in section I.  For 
purposes of this guidance, we use the terms firm or you to refer to these parties. 
   
 
11 See FDAs final rule Postmarketing Safety Reports for Human Drug and Biological Products; Electronic 
Submission Requirements (79 FR 33072, June 10, 2014), promulgating the requirements set forth in 21 CFR 
310.305(e),  314.80(g), 314.98, 329.100(c), 600.2, 600.80(h), 600.81(b)(1), and 600.90.   
12 FDA delayed the June 10, 2015, compliance date to September 8, 2015, in the final rule Postmarketing Safety 
Reports for Human Drug and Biological Products; Electronic Submission Requirements; Delay of Compliance Date; 
Safety Reporting Portal of Electronic Submission of Postmarketing Safety Reports for Human Drugs and 
Nonvaccine Biological Products (80 FR 30151, May 27, 2015).   
13 Section 745A(a) of the FD&C Act (21 U.S.C. 379k-1) provides that submissions under section 505(b), (i), or (j) 
of the FD&C Act or section 351(a) or (k) of the Public Health Service Act shall be submitted in such electronic 
format as specified by FDA in guidance.  In section 745A(a), Congress granted explicit statutory authority to FDA 
to implement the electronic format for submissions requirement by guidance.  This grant of authority, however, did 
not preclude FDA from implementing such requirements by notice and comment rulemaking (5 U.S.C. 553).  
Accordingly, even though FDA concluded that certain submissions that are addressed in the June 10, 2014, final rule 
are also within the scope of section 745A(a) of the FD&C Act, FDA determined that it was appropriate to amend the 
regulations on the submission of postmarketing safety reports through notice and comment rulemaking to remove 
references to paper submissions and to specify that such reports be submitted in an electronic format that FDA can 
process, review, and archive (see 79 FR 33072, June 10, 2014).  This guidance is not issued under section 745A of 
the FD&C Act and does not establish legally enforceable responsibilities.  To the extent it discusses binding 
requirements, such requirements have been promulgated in previously issued FDA regulations. 
14 See 79 FR 33200 (June 10, 2014). 
  3  Contains Nonbinding Recommendations 
 
III.  ICSR SUBMISSIONS 
 
A.  General Information  
 
An Individual Case Safety Report (ICSR) is a description of an adverse drug experience15 related 
to an individual patient or subject.16  An ICSR is made up of data elements, such as the date of an 
adverse drug experience, the name of a suspect medical product, and the name of the initial 
reporter.  These data elements are listed in the relevant regulations.17  The information described 
by the data elements should be included in the ICSR submission if available and applicable to the 
report. 
 
An initial ICSR describes the adverse drug experience originally reported to the firm. 
 
An ICSR attachment is a document related to an adverse drug experience described in an ICSR, 
such as relevant hospital discharge summaries and autopsy reports or death certificates (see 21 
CFR 314.80(a) and 21 CFR 600.80(a)).  ICSR attachments may also include published articles 
for ICSRs based on scientific literature (see 21 CFR 314.80(d) and 21 CFR 600.80(d)), and the 
product label (see 21 CFR 310.305(c)(1) and section 760(b)(1) of the FD&C Act (see also 
section V.E.)). 
 
A follow-up ICSR includes new information about an adverse drug experience that has been 
previously reported as an initial ICSR.  It should provide a complete picture of the current 
understanding of an adverse drug experience, rather than providing only the changes and/or 
updates to an initial ICSR.  Accordingly, follow-up ICSRs should include information about an 
adverse drug experience that has been previously reported along with any new information.  
However, to avoid duplication, any ICSR attachments submitted with an initial ICSR (e.g., 
literature articles, hospital discharge summaries) should not be resubmitted with a follow-up 
ICSR unless there are updates to the information. 
 
The procedures for electronic submission of initial and follow-up ICSRs and ICSR attachments 
for all of these types of reports are the same.18 
 
 
15 See 21 CFR 314.80(a).  For purposes of this guidance, the term adverse drug experience also refers to adverse 
experience within the meaning of 21 CFR 600.80(a), which is defined as any adverse event associated with use of a 
biological product in humans, whether or not considered product related. 
16 21 CFR 310.305(b),  314.80(a) and 600.80(a); see also 21 CFR 329.100(b). 
17 21 CFR 310.305(d),  314.80(f), 329.100(b)(1), and 600.80(f). 
18 An applicant whose product is a combination product that contains a device constituent part and was approved 
under an ANDA, NDA, or BLA must also submit other reports (e.g., Five-day reports and Malfunction reports), in 
addition to the postmarketing safety reports associated with the application type, in accordance with 21 CFR part 4, 
subpart B (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-
reporting-combination-products for additional information).  As discussed in the guidance Postmarketing Safety 
Reporting for Combination Products: Guidance for Industry and FDA Staff (July 2019), ICSRs for combination 
products describe a report of an event experienced by an individual user of a combination product, including adverse 
events and malfunctions, and encompass the following types of reports:  Fifteen-day reports (see 21 CFR 314.80 and 
600.80), Five-day reports (see 21 CFR 803.3,  803.53 and 803.56), Malfunction reports (see 21 CFR 803.50 and  
803.56), and reports of deaths or serious injuries (see 21 CFR part 803).   
  4  Contains Nonbinding Recommendations 
  15-day alert reports required under 21 CFR 314.80(c)(1),  600.80(c)(1), and 
310.305(c), including for prescription drug products that are compounded by facilities 
registered as outsourcing facilities under section 503B of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) 
 
  Reports for serious, expected, and non-serious adverse drug experiences required under                       
21 CFR 314.80(c)(2)(ii)(B) and 21 CFR 600.80(c)(2)(ii)(B) 
 
  Serious adverse event reports required under section 760 of the FD&C Act   
 
  Five-day reports for combination products with a device constituent part required under 
21 CFR 4.102(b)(1),  4.102(c)(1)(i), 803.53, and 803.56 
 
  Malfunction reports for combination products with a device constituent part required 
under 21 CFR 4.102(b)(1),  4.102(c)(1)(ii), 803.50, and 803.56 
 
B.  Options for Electronic Submission of ICSRs: Electronic Submissions 
Gateway or Safety Reporting Portal  
 
ICSRs and ICSR attachments for human drugs, biological products, and combination products 
addressed by this guidance are submitted to the FDA Adverse Event Reporting System (FAERS) 
database.  FDA provides two options for electronic submission of ICSRs and ICSR attachments 
to FAERS: (1) direct submission through the Electronic Submissions Gateway (ESG) or (2) 
submission through the Safety Reporting Portal (SRP), both of which are available 24 hours a 
day, 7 days a week. 
 
Direct submission through the ESG is described on the FAERS Electronic Submissions web 
page.19  This option involves direct transmission of ICSRs from a firms database to FDA 
through the ESG.  The ESG is a central transmission point for sending information electronically 
to FDA.  Once received through the ESG, the submitted reports are processed into the FAERS 
database.  For instructions on organizing, preparing, and submitting ICSRs and ICSR 
attachments using the direct submission method through the ESG, see the technical 
specifications document available on the FAERS Electronic Submissions web page.  The 
technical specifications document is incorporated by reference into this guidance document and 
addresses topics such as data elements, electronic transport format, and types of ICSR 
attachments FDA currently accepts.   
 
The submission of ICSRs and ICSR attachments through the SRP is described on the FDA SRP 
web page.20  Users enter the ICSR information manually into a web-based form and this 
information is then submitted to FDA to be uploaded into the FAERS database.   
 
 
19 See the FAERS Electronic Submissions web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm115
894.htm. 
20 See FDAs SRP web page at https://www.safetyreporting.hhs.gov. 
  5  Contains Nonbinding Recommendations 
C.  Create an Account Before Submitting Electronically for the First Time 
 
To submit postmarketing safety reports electronically, either through the ESG or SRP, you 
should create an account with FDA if you have not previously established one.  To create an 
account, you should notify the FAERS Electronic Submission Coordinator of your intent at 
faersesub@fda.hhs.gov.  The FAERS Electronic Submission Coordinator will assist you in 
creating an account and ensuring that all steps have been completed for successful submission of 
postmarketing safety reports. 
 
D.  Unique Case Identification Numbers for ICSRs 
 
Postmarketing safety reporting often involves submitting a series of reports consisting of initial 
and follow-up ICSRs, along with any associated attachments, over the life cycle of an individual 
case.  Each ICSR includes a unique case identification number, which must be the same in an 
initial report and any subsequent follow-up reports.21   
  Via the SRP.  The SRP automatically generates a unique case identification number for 
an ICSR upon the submission of the initial ICSR.  When submitting follow-up ICSRs 
to the SRP for initial ICSRs submitted on paper, the firm should use the manufacturer 
control number assigned to the initial ICSR when inputting the unique case 
identification number in the SRP.  
 
  Via the ESG.  Before submitting an initial ICSR via the ESG, the firm assigns a unique 
case identification number for the ICSR.  When submitting follow-up ICSRs to the 
ESG for initial ICSRs submitted on paper, the firm should use the manufacturer control 
number assigned to the initial ICSR when inputting the unique case identification 
number in the ESG. 
 
  On paper (e.g., Form FDA 3500A or the CIOMS I form).22  Before submitting an 
initial ICSR on paper, the firm assigns the manufacturer control number as the unique 
case identification number.  
 
The same unique case identification number must be used for an initial ICSR and any follow-up 
ICSRs,23 even if there is a transfer of ownership of an application or unapproved drug product, to 
ensure that the follow-up ICSR can be matched with the initial submission. 
 
Firms should not submit follow-up ICSRs to the SRP if an initial report was submitted through 
the ESG.  Instead, follow-up reports should be submitted through the ESG to maintain the unique 
case identification number of the initial case.  If an initial report was submitted through the SRP, 
a follow-up report may be submitted to the ESG.  In this circumstance, the follow-up ICSR must 
 
21 See 21 CFR 310.305(d)(5)(vii),  314.80(f)(5)(viii), 329.100(b)(5)(vii), 600.80(f)(5)(viii), and 600.80(g)(7)(viii).  
The unique case identification number is used to track ICSRs and is distinct from the unique code for identification 
of the patient that should be assigned to protect the identity of the patient under 21 CFR 310.305(d)(1)(i),  
314.80(f)(1)(i), 329.100(b)(1)(i), and 600.80(f)(1)(i)). 
22 Prior to the implementation of the final rule requiring electronic submission of postmarketing safety reports, firms 
submitted ICSRs on Form 3500A or the CIOMS I form (see 79 FR 33072, June 10, 2014). 
23 See 21 CFR 310.305(d)(5)(vii),  314.80(f)(5)(viii), 329.100(b)(5)(vii), 600.80(f)(5)(viii), and 600.80(g)(7)(viii). 
  6  Contains Nonbinding Recommendations 
include the unique case identification generated by the SRP upon submission of the initial 
ICSR.24  
 
E.  Submitting Labeling and Labels for Unapproved Products 
 
For prescription drugs marketed for human use without an approved application, 15-day alert 
reports required under 21 CFR 310.305(c)(1) must be accompanied by the current content of 
labeling in electronic format as an ICSR attachment unless it is already on file at FDA.   
 
Similarly, for nonprescription drug products without an approved application, each report of a 
serious adverse event associated with such drug when used in the United States required under 
section 760(b)(1) of the FD&C Act must be accompanied by a copy of the label on or within the 
retail package of the drug (21 U.S.C. 379aa(b)(1)).   
 
For unapproved prescription and nonprescription drug products, labeling and labels should be 
submitted as ICSR attachments, unless they are already on file at FDA in Structured Product 
Labeling format as part of the electronic drug establishment registration and listing process.25  If 
the labeling or label is already on file, you should indicate so in the narrative of the ICSR. 
 
F.  Single Submission Versus Batched Submissions of ICSRs 
 
When submitting ICSRs through the ESG, you can submit ICSRs either as an individual report 
or several individual reports in a batch.  Please refer to the technical specifications document  
available on the FAERS Electronic Submissions web page for information on submitting an 
individual report reports versus several individual reports in a batch through the ESG.   
 
If you are submitting ICSRs through the SRP, please submit a single ICSR at a time.  The SRP is 
not able to process a batched submission.  
 
G.  Submitting ICSR Attachments  
 
Please submit ICSR attachments through the ESG only after your associated ICSR has been 
submitted and accepted by FAERS.  When submitting ICSRs and ICSR attachments through the 
SRP, firms may include the ICSR attachment at the same time they submit the ICSR. 
 
 
IV.  NOTIFICATION OF RECEIPT OF SUBMISSIONS BY FDA 
 
A.  ESG Message Delivery Notices and FAERS Acknowledgements 
 
Once a submission (one or more ICSRs or ICSR attachments) is successfully recognized and 
decrypted, an ESG message delivery notice (MDN) is sent to the submitter.  The date of this 
 
24 See 21 CFR 310.305(d)(5)(vii),  314.80(f)(5)(viii), 329.100(b)(5)(vii), 600.80(f)(5)(viii), and 600.80(g)(7)(viii). 
25 See FDAs May 2009 for industry Providing Regulatory Submissions in Electronic FormatDrug Establishment 
Registration and Drug Listing, and FDAs Structured Product Labeling Resources at www.fda.gov/industry/fda-
data-standards-advisory-board/structured-product-labeling-resources.  
  7  Contains Nonbinding Recommendations 
MDN generally serves as the official FDA receipt date of each successfully transmitted ICSR 
and ICSR attachment in the submission (see FDAs ESG web page for further information about 
receipt of submissions through the ESG).26   
 
After receipt of the submission, the ICSR and ICSR attachments are processed into the FAERS 
database and a second automated acknowledgement message, the FAERS acknowledgement, is 
sent to the submitter via the ESG.  The FAERS acknowledgement provides the sender the status 
of each ICSR and ICSR attachment in the transmission.  You should expect to receive the ESG 
MDN and FAERS acknowledgements within 24 hours after you have submitted an ICSR or 
ICSR attachment.  If you do not receive the acknowledgement within 24 hours, you should first 
check the ESG System Status on FDAs web page at https://www.fda.gov/esg to determine 
whether we are experiencing any problems with the ESG and if so, please see section V. of this 
guidance, which describes the contingencies when the ESG is not functional.   
 
If the ESG is functional and you are notified that FAERS could not load your submission 
(e.g., because the ICSR lacks the electronic transport formats that FDA supports), the FAERS 
acknowledgement will indicate that FDA could not load the submission into FAERS.  You 
should resubmit to FDA any ICSRs or ICSR attachments that were not processed into FAERS.  
Your resubmission should be given a different file name than the original submission and must 
take place within any required reporting timeframe.27  The date of the ESG MDN for the 
resubmission will serve as the official FDA receipt date of the ICSR or ICSR attachments. 
 
If the ESG is functional but you do not receive the MDN, you should contact the FAERS 
Electronic Submission Coordinator at faersesub@fda.hhs.gov to determine why you have not 
received the MDN.  If you are notified to resubmit the ICSRs and ICSR attachments, you must 
do so within any required reporting timeframe.28  The date of the ESG MDN for the 
resubmission will serve as the official FDA receipt date of the ICSR or ICSR attachments.   
 
Additional information on the receipt date of submissions when submitting through the ESG is 
available in the guidance for industry Providing Regulatory Submissions in Electronic Format
Receipt Date (February 2014).   
 
B.  SRP Acknowledgment 
 
After the ICSR, with or without ICSR attachments, is submitted via the SRP, an 
acknowledgement email is sent immediately to the user.  The acknowledgement email indicates 
successful transmission of the report.  If the ICSR did not transmit, the user will not receive an 
acknowledgement email.  In this situation, the user should contact the FAERS Electronic 
Submission Coordinator at faersesub@fda.hhs.gov for assistance.  The date of the 
acknowledgement email serves as the official FDA receipt date of the submission. 
 
 
 
26 See FDAs ESG web page at 
https://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/AboutESG/default.htm.  
27 See 21 CFR 310.305,  314.80 and 600.80, and section 760 of the FD&C Act.   
28 Id. 
  8  Contains Nonbinding Recommendations 
V.  CONTINGENCIES WHEN THE ESG, FAERS, OR SRP IS TEMPORARILY 
UNAVAILABLE 
 
As described in section IV. of this guidance, you should expect to receive your 
acknowledgements (i.e., ESG MDN, FAERS acknowledgement, or SRP acknowledgement) 
within 24 hours after submitting an ICSR or ICSR attachment. 
 
A.  Contingencies When Submitting Through the ESG 
 
If you submit through the ESG and do not receive the acknowledgement within 24 hours, you 
should check the ESG System Status on FDAs web page at https://www.fda.gov/esg.  If the 
ESG is not functional, FDA intends to notify all companies with an ESG account by email.  FDA 
also intends to notify companies by email when ESG functionality is restored.   
 
If the ESG is not functional for more than 48 hours and you choose to submit your ICSRs or 
ICSR attachments on physical media, FDA requests that your submission be in the current 
version of the International Council for Harmonisation (ICH) E2B format supported by FDA.29  
In this circumstance, you should not resubmit the ICSRs or ICSR attachments to FDA using the 
ESG or SRP when the ESG becomes functional.  (See section V.D. for additional information on 
submitting on physical media.) 
 
If the ESG is functional but FAERS is not functional, you should expect to receive the MDN 
but not the FAERS acknowledgement.  FDA intends to load your ICSRs or ICSR attachments 
into FAERS as soon as FAERS is functional.  At that time, you should expect to receive the 
FAERS acknowledgement.  You should not submit your ICSRs or ICSR attachments to FDA by 
other means (i.e., physical media or the SRP).  The ESG MDN for the ICSRs or ICSR 
attachments will serve as the official FDA receipt date of the ICSR.  
 
B.  Contingencies When Submitting Through the SRP 
 
If the SRP is not functional, users will not be able to log in to submit an ICSR.  You should 
contact the FAERS Electronic Submission Coordinator at faersesub@fda.hhs.gov for assistance. 
 
C.  Receipt Dates 
 
If you submitted your ICSR when the ESG, FAERS, or SRP was temporarily unavailable, and 
the FDA receipt date for the resubmission is after the required reporting timeframe, FDA will 
work with you to reset the FDA receipt date.  In this case, you should retain documentation 
showing that you submitted the ICSRs or ICSR attachments within the required reporting 
timeframe. 
   
 
29 See ICH E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs) Implementation Guide
Data Elements and Message Specification, available at FDAs guidance web page.  
  9  Contains Nonbinding Recommendations 
 
D.  Physical Media as a Backup Method 
 
FDA recommends that physical media be used only as a backup method for electronic 
submission of ICSRs or ICSR attachments when the ESG is not functional for more than 48 
hours.  If submitting on physical media, you should provide the information in the current 
version of the ICH E2B format supported by FDA.  For CDER-regulated products, FDA 
recommends that you contact the FAERS Electronic Submission Coordinator at 
faersesub@fda.hhs.gov if you are considering sending ICSR files on physical media.  For 
CBER-regulated products, you should contact the CBER Electronic Submissions Director at 
esubprep@fda.hhs.gov. 
 
For submissions sent on physical media, the Agency generally determines the receipt date as it 
does for submissions sent to FDA on paper.  The receipt date is the date it arrives by mail at the 
Agency.  The Agency intends to contact you by telephone or email within 3 business days after 
receipt of the physical media submission if there are problems with the format of the report, or if 
it cannot be processed into FAERS, and to request resubmission of the report in the proper 
format.  You should resubmit the reports as soon as possible.  The receipt date of the 
resubmission will serve as the official FDA receipt date of the report. 
 
VI.  DESCRIPTIVE INFORMATION IN PERIODIC SAFETY REPORTS  
 
For purposes of this guidance, a periodic safety report required under 21 CFR 314.80(c)(2) or 21 
CFR 600.80(c)(2) is considered to have two parts: 
 
  Descriptive information 
 
  ICSR(s) and ICSR attachment(s) 
 
The descriptive information in these periodic safety reports must be submitted in an electronic 
format the Agency can process, review, and archive.30  The Electronic Common Technical 
Document (eCTD)31 is the format FDA accepts for submission of the descriptive portion. 
 
ICSRs and ICSR attachments should not be submitted to the eCTD because ICSRs submitted to 
the eCTD will not be processed into the FAERS database.  (See section III. of this guidance for 
information on how to submit ICSRs and ICSR attachments.) 
 
VII.  WAIVER REQUESTS 
 
Any person required to submit a postmarketing safety report under 21 CFR 310.305,  314.80, 
314.98, 600.80, or section 760 of the FD&C Act may ask FDA to waive temporarily the 
 
30 See 21 CFR 314.80(g)(1) and 21 CFR 600.80(h). 
31 Information regarding the eCTD is available on FDAs web page at 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ 
ucm153574.htm. 
  10  Contains Nonbinding Recommendations 
requirement that the safety report be submitted in electronic format.32  We anticipate that 
temporary waivers will be needed only in rare circumstances. 
 
A.  Content of Waiver Requests 
 
The request to waive the requirement to submit reports in electronic format must be made in 
writing,33 and should be in a single letter and reference all products (with or without 
applications) that would be covered by the electronic submission waiver.  The waiver request 
should include the reason for the request and information justifying the waiver.  Reasons could 
include, for example, acts of nature, widespread Internet outages, and critical issues with a firms 
safety database(s), such as malware attacks.  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.   
 
B.  Where to Submit Waiver Requests 
 
CDER Products 
 
For products with an approved application that are regulated by CDER, submit your waiver 
requests to the application in the eCTD34 format, if you have the capability to do so.  The 
requests should be addressed to the Director of CDERs Office of Surveillance and 
Epidemiology (OSE).  If you do not have the capability to electronically transmit a waiver 
request to the eCTD, you may contact OSEs Regulatory Affairs Staff by email at 
OSE.PMKTREGS@fda.hhs.gov to discuss how to submit your waiver request.  You should 
indicate in the subject line of your letter or email that you are requesting a waiver of the 
electronic reporting requirement under 21 CFR 314.80(e)(2) or 21 CFR 600.80(h)(2), as 
appropriate.   
 
For drug products marketed without an approved application, you may contact OSEs Regulatory 
Affairs Staff by email at OSE.PMKTREGS@fda.hhs.gov.  You should indicate in the subject 
line of your email that you are requesting a waiver of the electronic reporting requirement under 
21 CFR 310.305(e)(2) or 21 CFR 329.100(c)(2), as appropriate. 
 
CBER Products 
 
For licensed biological products regulated by CBER, waiver requests should be addressed to: 
 
Document Control Center  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
 
32 Requests for waivers under 21 CFR 310.305(e)(2),  314.80(g)(2) or 329.100(c)(2) should be submitted as 
described in this guidance.  Requests for waivers under 21 CFR 600.80(h)(2) or 21 CFR 600.81(b)(2) must be 
submitted in accordance with 21 CFR 600.90 and should be submitted as described in this guidance. 
33 21 CFR 310.305(e)(2),  314.80(g)(2), 329.100(c)(2), and 600.80(h)(2). 
34 Information about the eCTD is available at the eCTD web page https://www.fda.gov/drugs/electronic-regulatory-
submission-and-review/electronic-common-technical-document-ectd. 
  11  Contains Nonbinding Recommendations 
10903 New Hampshire Avenue 
Building 71, Room G112 
Silver Spring, MD  20993-0002 
 
C.  FDA Response to Waiver Requests 
 
FDA reviews waiver requests on an individual basis.  The Agency plans to respond in writing to 
the requestor, stating whether the waiver is granted.  If the waiver is granted, the response will 
include the agreed upon alternative method for submission as well as the end date of the waiver.  
Waivers of the requirement to submit reports in electronic format, if granted, will be temporary. 
 
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