Guidance for Industry 

Postmarketing Adverse Event 
Reporting for Nonprescription 

Human Drug Products Marketed 

Without an Approved Application  

 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

July 2009 
OTC 
 
 
OMB Control Number 0910-0636 

Expiration Date: 06/30/2012 

See additional PRA statement in Section VI of this guidance 

   
Guidance for Industry 

Postmarketing Adverse Event 

Reporting for Nonprescription 

Human Drug Products Marketed 

Without an Approved Application 

 
 
 
 
 
 
 
 
Additional copies are available from 
 
: 

Office of Communications 
 
Division of  Drug Information, WO51, Room  2201 
 
10903 New Hampshire Ave. 

Silver Spring, MD 20993 
 
Phone: 301-796-3400;  Fax: 301-847-8714 
 
druginfo@fda.hhs.gov 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
July 2009 

OTC 

 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
I.   INTRODUCTION............................................................................................................. 4 
 
II.   BACKGROUND ............................................................................................................... 4 
 
III.   MINIMUM DATA ELEMENTS FOR AN INDIVIDUAL CASE SAFETY REPORT 

(ICSR) ............................................................................................................................................ 6 
 
A.   Initial ICSR Submission................................................................................................................6
  
1. Identifiable Patient..........................................................................................................................7
  
2.  Identifiable Reporter........................................................................................................................8
  
3.  Suspect Drug....................................................................................................................................8
  
4.  Serious Adverse Event....................................................................................................................10
  
B.   Submission of New Medical Information (Follow-up Reports)...............................................11
  
IV.    SUBMITTING THE LABEL ........................................................................................ 12 
 
V.   REPORTING FORMATS FOR PAPER OR ELECTRONIC SUBMISSIONS ...... 12 
 
A.   Paper Submission (FDA Form 3500A) ......................................................................................13
  
1.  Acquiring Copies of FDA Form 3500A.........................................................................................13
  
2.  Generating Copies of FDA Form 3500A.......................................................................................13
  
3.  Completing FDA Form 3500A.......................................................................................................13
  
4. Submitting FDA Form 3500A.........................................................................................................14
  
B.   Electronic Submission .................................................................................................................14
  
VI.   PAPERWORK REDUCTION ACT OF 1995.............................................................. 15 
 
APPENDIX 1:   FDA FORM 3500A .......................................................................................... 16 
 
  Contains Nonbinding Recommendations 
 
 
1
 
Guidance for Industry  
Postmarketing Adverse Event Reporting for  

Nonprescription Human Drug Products Marketed Without an 

Approved Application 

 
 
 
 
This guidance represents the Food and Drug Administration's (FDAs) current thinking on this topic.  It 
does not create or confer any rights for or on any  person and does not operate to bind FDA or the public.  
An alternative approach may be used if such approach satisfies the requirements of the applicable statutes 
and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
I.  INTRODUCTION  
 
This document provides guidance to industry on postmarketing serious adverse event reporting 
for nonprescription (over-the-counter (OTC)) human drug products marketed without an 
approved application. In particular, this document gives guidance on (1) the minimum data 
elements that should be included in a serious adverse event report, (2) the label that should be 
included with the report, (3) reporting formats for paper and electronic submissions, and (4) how 
and where to submit the reports.  
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited. The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
 
II.  BACKGROUND 
 
Public Law 109-462, the Dietary Supplement and Nonprescription Drug Consumer Protection 
Act, was signed by the President on December 22, 2006. 2  Public Law 109-462 amends the 
                                                 
 
1 This guidance has been  prepared by the Office of Surveillance and Epidemiology in the Center for Drug  
Evaluation and Research (CDER) at the Food and Drug Administration.  
 
2 See: http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ucm102797.pdf. 
  4
 
  Contains Nonbinding Recommendations 
 
Federal Food, Drug, and Cosmetic Act (the Act) to add safety reporting requirements for OTC 
drug products that are marketed without an approved application under section 505 of the Act 
(21 U.S.C. 355).3  Before the enactment of Public Law 109-462,  only those OTC drugs marketed 
with an application approved under section 505 of the Act were subject to mandatory 
postmarketing safety reporting requirements.4  As required by section 2(e)(3) of Public Law 109-
462, we are issuing this guidance to describe the minimum data elements for the required 
reports.5  This guidance also describes relevant policies and procedures for making these reports. 
 
The manufacturer, packer, or distributor6 whose name (under section 502(b)(1) of the Act (21 
U.S.C. 352(b)(1))) appears on the label of an OTC drug marketed in the United States without an 
approved application (referred to as the responsible person) must submit to FDA any report 
received of a serious adverse event associated with such drug when used in the United States, 
accompanied by a copy of the label on or within the retail package of such drug (section 
760(b)(1) of the Act). In addition, the responsible person must submit follow-up reports of new 
medical information related to a submitted serious adverse event report that is received within 1 
year of the initial report (section 760(c)(2) of the Act).  Serious adverse event reports received 
through the address or telephone number described on the product label, as well as all follow-up 
reports of new medical information, must be submitted to FDA no later than 15 business days 
after a report of a serious adverse event or the new medical information is received by the 
responsible person (section 760(c)(1) and 760(c)(2) of the Act).  We recommend that all serious 
adverse event reports received by the responsible person be submitted to FDA within 15 business  
days of receipt.7    
                                                                                                                                                             
 
 
3 Section 760  of the Act (21 U.S.C.  379aa), as amended, provides for mandatory safety reporting for OTC human 
drug products not subject  to  applications approved under  section 505 of  the Act (new drug  applications (NDAs) or  
abbreviated new drug applications (ANDAs)).  Accordingly, these new requirements apply to all OTC  drug products  
marketed without an approved application, including those  marketed under the OTC Drug Monograph  Review 
process (whether or not subject to a final monograph), those marketed outside the monograph system, and including 
those that have been  discontinued from  marketing but for which a report of an adverse event was received.  These 
reporting requirements became effective December 22, 2007. 
 
4 Postmarketing safety reporting  requirements for  drugs marketed  under an  approved application, including OTC 
drugs, are set  forth at  21 CFR 314.80 and 314.98. 
 
5 Public Law 109-462 states that Not later than 270 days  after the date of enactment of this Act, the Secretary of  
Health and Human Services shall issue guidance on the minimum data elements that should be included in a serious 
adverse event report as described under the amendments  made by this  Act (section 2(e)(3)).  Public Law 109-462 
also requires certain postmarketing safety  reports for dietary supplements.  The Center for Food Safety and Applied 
Nutrition is issuing a separate guidance on reporting for dietary supplements. 
 
6 Under section 760(b)(2) of the Act, a retailer whose name appears on the  label as a distributor may, by agreement,  
authorize the manufacturer or packer of the OTC drug to satisfy the retailers safety reporting  obligations under the 
Act. If the retailer enters into such an agreement, and the retailer complies with its obligation to direct to the 
manufacturer  or  packer all adverse events  associated  with such drug that are reported to the retailer, the retailer need  
not  submit any required reports to FDA under section 760(b)(1) of the Act.  
 
7 Section 760(c)(1)  of the Act,  which contains the 15-day deadline for submitting serious adverse event  reports to  
FDA, expressly applies to serious adverse event reports resulting from information received by the responsible 
person through the address or  telephone  number on the product label.  Although the Act does not expressly provide  
  5
 
  Contains Nonbinding Recommendations 
 
 
The information on data elements included in this document is consistent to the extent possible 
with guidance on data elements for a safety report for applicants of approved NDAs, ANDAs, 
and antibiotic applications; manufacturers of marketed prescription drugs for human use without 
approved NDAs or ANDAs; and licensed manufacturers of approved biologic product license 
applications (BLAs).8   
  
 
III. 	 MINIMUM DATA ELEMENTS FOR AN INDIVIDUAL CASE SAFETY REPORT 
(ICSR) 
 
A. 	 Initial ICSR Submission 
 
As discussed in section II of this document, section 760(b)(1) of the Act, as amended, requires 
responsible persons to submit to FDA any report received of a serious adverse event associated 
with the use of an OTC drug marketed in the United States without an approved application 
when the product is used in the United States.  The person who first notifies the responsible 
person about an adverse drug event is the reporter. Reporters can include patients, relatives of 
patients, consumers, doctors, pharmacists, other health care practitioners, or other individuals. 
 
Reporters convey information on adverse events to the responsible person by various means, 
including phone, the Internet, fax, e-mail, or regular mail.  Based on the information from the 
reporter and any other information received or obtained on the adverse event, the responsible 
person completes an ICSR in one of the formats described in section V of this document and 
submits it to FDA.     
 
To complete an ICSR, responsible persons should provide all known or reasonably known 
applicable elements on FDA Form 3500A or its electronic equivalent identified by FDA for 
electronic reporting. Applicable elements on FDA Form 3500A include all sections except those 
                                                                                                                                                             
 
a timeframe for serious adverse event reports that the responsible person receives by other means (such as by e-mail 
or fax), the reporting of such  adverse events  is required  by the plain language of section 760(b)(1) (providing that  
the responsible person shall submit . . . any report received of a serious adverse event associated with such drug 
when  used in the United States . . . . (emphasis added)).   Prompt submission of serious adverse event reports is  
important  for public  health  reasons.  Delayed reporting of some serious adverse events to FDA solely because of the 
medium through  which the adverse event  was reported to the responsible person  would lessen the effectiveness of  
adverse event reporting as a tool for FDA to detect and alert the public to possible safety problems.  Therefore, the 
agency strongly recommends that all serious adverse event reports received by the responsible person, regardless of 
the means by which the report was received, be submitted within the same timeframe as reports received by phone  
or mail, i.e., within 15 business days of their receipt by the responsible person.  
 
8 See the guidance for industry, Postmarketing Adverse Experience Reporting for Human Drug and Licensed 
Biological Products: Clarification of  What to Report, available on the Internet at http://www.fda.gov/Drugs  under  
Guidances . In March 2001 (66 FR 14391),  the Agency also made available a draft  guidance document on  
Postmarketing Safety Reporting for Human Drug  and Biological Products Including Vaccines. When finalized, the 
guidance will provide recommendations on  this topic.  We update guidances periodically.  To make sure you have  
the most recent version of guidances, check the CDER guidance page at http://www.fda.gov/Drugs. 
 
  6
 
  Contains Nonbinding Recommendations 
 
identified as  for device manufacturers only (i.e., all sections except D, F, and H). See 
Appendix 1 for the specific elements on FDA Form 3500A.   
 
The quality of reports of serious adverse events submitted to FDA is critical for appropriate 
evaluation of the relationship between the product and adverse event(s).9  FDA recommends that 
responsible persons make a reasonable attempt to obtain complete information for case 
assessment during initial contacts and subsequent follow-up.  FDA encourages responsible 
 
persons to use trained health care practitioners to query reporters, computer-assisted interview 
technology, targeted questionnaires, and/or other methods developed to target specific events 
that help focus the line of questioning.  When the reporter is a patient or consumer, the 
responsible person should attempt to contact the health care practitioner familiar with the 
patients adverse event, with the patient/consumer's permission, to obtain further medical 
information and to retrieve relevant medical records, if appropriate.   
 
FDA considers all of the applicable elements on FDA Form 3500A or its electronic equivalent as 
critical for case assessment. In order for FDA to avoid duplication, interpret significance, 
facilitate follow-up, and detect fraud, at a minimum, the four data elements listed in the bullets 
below should be included in any serious adverse event report for an OTC drug product that is 
marketed without an approved application:     
 
   an identifiable patient  
   an identifiable reporter 
   a suspect drug 
   a serious adverse event or fatal outcome 
 
The responsible person should actively seek information on any minimum data element not 
initially provided by the reporter. The responsible person should not submit a report on the 
incident to FDA unless and until each minimum data element is obtained.  FDA does not intend 
to take enforcement action for failure to submit a report for a serious adverse event where, after 
due diligence, the responsible person is unable to obtain one or more of the four minimum data 
elements.  The responsible person should maintain records of the event information and its 
efforts to obtain the basic elements for an individual report in its files.  In addition, the 
responsible person should actively seek follow-up information for the purposes of completing all 
the applicable elements for an ICSR and document its efforts to obtain this additional relevant 
information.  The responsible person must maintain records related to any adverse event report it 
receives (regardless of whether the adverse event must be reported to FDA and including 
documentation of its efforts to obtain the minimum data elements) for a period of 6 years and 
allow FDA to access the records (section 760(e) of the Act).   
 
1.  Identifiable Patient 
 
                                                 
 
9 See the guidance for industry on Good  Pharmacovigilance Practices and Pharmacoepidemiologic Assessment, 
available at http://www.fda.gov/Drugs  under Guidances.  
 
  7
 
  Contains Nonbinding Recommendations 
 
To have an identifiable patient, there should be enough information to indicate the 
existence of a specific patient or consumer.  One or more of the following automatically 
qualifies a patient as identifiable: age (or age category, e.g., adolescent, adult, elderly), 
gender, initials, date of birth, name, or patient identification number.  A report stating that 
an elderly woman had anaphylaxis or a young man experienced anaphylaxis would 
be sufficient. If a report received by the responsible person refers to groups of unknown 
size, such as some or a few college students got anaphylaxis, the responsible person 
should follow up to find out the number and then submit a separate report to FDA for 
each identifiable patient.  The responsible person should distinguish each patient so that it 
is clear that each ICSR is not a duplicate report of a single adverse event.  
 
Patients should not be identified by name or address when reporting to FDA.  Instead, the 
responsible person should assign a code (e.g., patient initials) to each ICSR.  The 
assigned code will permit the responsible person to cross-reference with identifying 
information and contact information in the event follow-up is sought.  
 
2.  Identifiable Reporter  
 
A reporter is the person who notifies the responsible person about the serious adverse 
event. A reporter can be the patient, consumer, family member, doctor, pharmacist, other 
health care practitioner, or other individual.  The responsible person should have 
sufficient information to indicate that there is an identifiable person who purports to have 
knowledge about the patient, adverse event and drug involved. Care should be taken to 
avoid submission of reports for which the reporter clearly lacks such knowledge.  
Individual judgment will be needed at times to decide whether or not a reporter should be 
considered identifiable for reporting purposes.  One or more of the following 
automatically qualifies a reporter as identifiable: a personal identifier (e.g., name), 
professional identifier (e.g., doctor, nurse, pharmacist), or contact information (e.g., e-
mail address, phone number).  When possible, the responsible person should attempt to 
obtain the reporters contact information for the responsible person and/or FDA to 
follow-up. If an identifiable reporter provides contact information but requests that the 
responsible person not forward this information to FDA, the responsible person can 
submit a report to FDA without specific identification of the reporter by filling in the 
reporter identity fields in  an ICSR with a statement such as Requested Anonymity.  
 
3.  Suspect Drug 
 
To provide the minimum amount of information needed to identify a suspect drug, the 
responsible person should have information on the active ingredient(s) used by the patient 
(e.g., acetaminophen and phenylephrine hydrochloride).  If the reporter cannot provide 
sufficient information for the responsible person to ascertain the active ingredient(s) used 
by the patient, then the reporter has not sufficiently identified a suspect drug.  For 
example, it would be insufficient for the reporter to provide a brand family name under 
which multiple products with different active ingredients are marketed, but not provide 
other product attributes to permit identification of the active ingredient. 
 
  8
 
  Contains Nonbinding Recommendations 
 
For reporting purposes, an ICSR should describe the known product attributes (e.g., 
dosage form, strength, color, SKU, NDC, lot number).  If a serious adverse event 
involves multiple suspect drug products that are manufactured, packaged, or distributed 
by the same responsible person, the responsible person should submit only one ICSR, 
according to the safety reporting requirements applicable to the drug product considered 
most suspect by the reporter.10  If the reporter views each product as equally suspect, the 
responsible person should submit only one ICSR, according to the safety reporting 
requirements applicable to the drug product that is first alphabetically.  In either case, the 
ICSR would include information on all suspect drug products with one manufacturer 
report number.   
 
If the serious adverse event is associated with an OTC drug product(s) marketed without 
an approved application and a dietary supplement(s) that is also manufactured, packaged, 
or distributed by the same responsible person, and the reporter views each product as 
suspect, the responsible person should submit the ICSR about the serious adverse event to 
both CDER and to CFSAN. The ICSR should identify both suspect products and use one 
manufacturer report number. 
 
If a serious adverse event involves multiple suspect drug products that were 
manufactured, packaged or distributed by more than one responsible person (e.g., 
manufacturer A and B), and if the event is reported to one of the responsible persons 
(manufacturer A), then that responsible person (manufacturer A) must submit an ICSR to 
FDA on the serious adverse event that describes detailed information, including  
information about manufacturer Bs product(s) and a copy of the label of manufacturer 
As suspect product(s) (see Section IV of this document).11  In such a case, we 
recommend that manufacturer A send manufacturer B a copy of the ICSR submitted to 
FDA, including manufacturer As report number.  In the event that manufacturer B 
receives such a report, manufacturer B must submit its own ICSR and a copy of the label 
of its suspect product(s), citing manufacturer As report number in the narrative section 
(i.e., section B.5 for reports submitted using FDA Form 3500A or its equivalent in the 
electronic format). 
 
                                                 
 
10 See section  760  of the Act (for OTC drug  products marketed  without an approved application), 21 CFR 310.305  
(for prescription drug  products marketed without an approved application), 21 CFR 314.80 (for drug  products  
marketed  under an  NDA), 21  CFR 314.98  (for drug  products marketed under an ANDA), 21 CFR 314.540 (for  drug  
products approved under Subpart H), or 21  CFR 600.80  (for drug  products marketed under a BLA). 
 
11 Section 760(b)(1) of the Act requires the manufacturer, packer, or distributor of a  nonprescription drug  marketed 
without an approved application to submit to FDA any report received of a serious adverse event associated with 
the drug when  used in the United States.  Accordingly,  when a report is required, responsible persons must  provide 
FDA with the information about the serious adverse event supplied  by the reporter.  Moreover, section 760(d)  of the 
Act requires serious adverse event  reports to  be submitted using the MedWatch form.  MedWatch Form 3500A, in  
existence when Public Law 109-463 was adopted, includes  section C, which seeks information about Suspect  
Product(s) known to the responsible  person.  Therefore, manufacturer A  must report information about  
manufacturer  Bs products in the example above even though manufacturer  A  did  not manufacture, package or  
distribute those products. 
  9
 
  Contains Nonbinding Recommendations 
 
4.  Serious Adverse Event 
 
A serious adverse event, as defined in section 760(a)(3) of the Act, must have one or 
more of the following patient outcomes or, based on reasonable medical judgment, 
require a medical or surgical intervention to prevent one of the following patient 
outcomes: 
 
   death 
   a life-threatening experience 
   inpatient hospitalization  
   a persistent or significant disability or incapacity  
   a congenital anomaly or birth defect 
 
Inpatient hospitalization includes initial admission to the hospital on an inpatient basis, 
even if released the same day, and prolongation of an existing inpatient hospitalization.   
 
Examples of serious adverse events that based on reasonable medical judgment should be 
treated medically or surgically to prevent one of the listed outcomes, include allergic 
bronchospasm that calls for intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.   
 
For reporting purposes, a serious adverse event  should, at a minimum, be described in 
terms of signs (including abnormal laboratory findings), symptoms, or disease diagnosis 
for purposes of reporting. Thus, a report stating that a patient experienced unspecified 
injury or a patient suffered irreparable damages would not be specific enough.  If the 
reporter does not provide any signs, symptoms, or diagnosis, responsible persons should 
obtain more information from that person, the patient, or (with the patients permission) 
medical professionals who treated the patient.  A report of a death, even without 
information about events that led to the death, meets the minimum description of a 
serious adverse event and should be reported to FDA.  Responsible persons should also 
provide any available information on the event(s) that led to the death. 
As part of the serious adverse event report, we encourage, as appropriate, attachment of 
the following: (1) hospital discharge summaries, (2) autopsy reports, (3) relevant 
laboratory data, and (4) other critical clinical data.   
 
The ICSR must be submitted within 15 business days of receipt of the report of the serious 
adverse event received through the address or phone number on the label (section 760(c)(1) of 
the Act).  The date the responsible person receives the four basic elements (i.e., identifiable 
patient, identifiable reporter, suspect drug, serious adverse event) is Day 0 of the 15-business-day 
time clock and should be entered into item G.4 of FDA Form 3500A or its electronic equivalent.   
 
Although the Act does not expressly require a responsible person to take action in the event that 
it receives reports of a serious adverse event in which the reporter identifies the suspect drug as 
one manufactured, packaged, or distributed by another responsible person, we recommend that 
such reports be promptly forwarded to that other responsible person.  A responsible person who 
  10
 
  Contains Nonbinding Recommendations 
 
receives a report of an adverse event regarding one of its products from another responsible 
person must submit an ICSR to FDA within the same timeframe applicable to any report 
received from a reporter (see section III.A.3 of this document).   
 
If a responsible person does not initially receive sufficient data for a report, but subsequently 
receives additional information completing the four basic elements concerning a serious adverse 
event, then an initial report should be submitted within 15 business days of the date the 
additional information was received, with the date that the additional information was received 
entered into item G.4 of FDA Form  3500A or its electronic equivalent. 
 
B.  Submission of New Medical Information (Follow-up Reports) 
 
The responsible person must submit a follow-up report when new medical information related to 
a submitted serious adverse drug event report is received by the responsible person within 1 year 
of the initial report (section 760(c)(2) of the Act).  Follow-up reports must be submitted no later 
than 15 business days after the new information is received by the responsible person (section 
760(c)(2) of the Act). Although not required under the statute, we recommend that responsible 
persons also submit a follow-up report if they receive new medical information related to a 
submitted serious adverse drug event after the 1-year period.  Responsible persons should 
provide a current, comprehensive understanding of the serious adverse drug event, rather than 
providing only the changes and/or updates to the initial report.  Relevant information from the 
initial report should be combined with the follow-up information to present an accurate and 
comprehensive, but concisely written, description of the event as it is understood at the time of 
the follow-up report.  This description and note of any changes or corrections to any fields 
should be provided in section B.5 for reports submitted using FDA Form 3500A or its equivalent 
in the electronic format.  
 
Any information from the initial report later found to be inaccurate should not be repeated in the 
follow-up report. All new information, including correction of previously submitted inaccurate 
information that is included in a follow-up report, should be highlighted.  To highlight new 
information or corrections included in follow-up reports submitted using FDA Form 3500A, use 
an asterisk, underline the information, or use other appropriate methods to indicate which 
information is new.  For example, if new dose information is received, it should be included in 
field C.1, and a statement such as Dose has been updated, underlined or highlighted with an 
asterisk, should be included in section B.5.  Any unchanged attachments submitted with an initial 
report (e.g., hospital discharge summaries, lab results) should not be resubmitted with a follow-
up report. 
 
If a new, serious adverse event occurs that is associated with the initial serious adverse event, a 
follow-up report should be submitted.  However, if the new, serious adverse event is not 
associated with the initial serious adverse event (e.g., occurs after a subsequent administration of 
the product), an initial report with a new manufacturer report number should be submitted for the 
new, serious adverse event and the manufacturer report number for the original serious adverse 
event should be included in the narrative section of the report.  In these cases, the responsible 
person should consider the clinical relevance of the serious adverse events to each other when 
determining whether an initial report or follow-up report should be submitted.  
  11
 
  Contains Nonbinding Recommendations 
 
 
Follow-up reports should use the same identification number as used in the initial ICSR (i.e., the 
number in section G.9 for reports submitted using FDA Form 3500A).  This allows the initial 
ICSR and all of its follow-up reports to be linked in FDAs Adverse Event Reporting System  
database (AERS) (see section V.B of this document for information on AERS).  The 
identification number used to submit follow-up reports to FDA should be the same as the 
identification number used in the initial ICSR, even if the responsible person reassigns 
identification numbers to internal files for submitted ICSRs (e.g., if duplicate reports are 
consolidated, or data handling procedures are changed).  No characters should be added to the 
initial manufacturer report number on submitted reports to denote that the report is a follow-up 
or to denote the sequence of the reports.  The initial identification number of the follow-up 
reports should continue to be used, but the reassigned internal identification number can be noted 
in the narrative section of the follow-up report (e.g., This event has been reassigned Company A 
ID number COA12345).   
 
 
IV.  SUBMITTING THE LABEL 
 
Each ICSR of a serious adverse event associated with an OTC drug marketed in the United 
States without an approved application must be accompanied by a copy of the label on or within 
the retail package of the drug (see section 760(b)(1) of the Act).  The responsible person should 
submit a copy of the full outer carton/container label and immediate container label (including 
the Drug Facts panel and the principal display panel) that are the same as the label on the drug 
product used, or most likely used, by the patient.  If the label has changed since the time of the 
adverse event, the responsible person may also submit a copy of the drugs current label.  For 
ICSRs submitted on paper (FDA Form 3500A), responsible persons should submit legible paper 
copies of these labels, no smaller than actual size, as an attachment to the form.  For ICSRs 
submitted in an electronic format, labels should be submitted in an appropriate electronic format 
that FDA can process, review, and archive (see section V.B of this document).  A copy of the 
label should not be resubmitted with a follow-up report unless there have been any changes to 
the label since the initial submission. 
 
 
V.  REPORTING FORMATS FOR PAPER OR ELECTRONIC SUBMISSIONS  
 
As described in section III of this document, under sections 760(b)(1) and (c)(2) of the Act, 
responsible persons must submit initial and follow-up ICSRs of serious adverse events associated 
with the use of OTC drugs marketed in the United States without an approved application when 
the products are used in the United States. In addition, as described in section IV of this 
document, under section 760(b)(1) of the Act, the report must be accompanied by a copy of the 
label on or within the retail package of the drug.  Responsible persons should use an FDA Form  
3500A or an electronic format to submit the ICSRs, as described below.   
 
This section describes how to (1) acquire, generate, complete, and submit an FDA Form 3500A 
for reporting ICSRs and (2) submit ICSRs and the copies of the label in an electronic format. 
 
  12
 
  Contains Nonbinding Recommendations 
 
A.  Paper Submission (FDA Form 3500A) 
 
1.  Acquiring Copies of FDA Form 3500A 
 
The form can be acquired from: 
 
 	  Appendix 1 of this guidance 
 
 	  the Internet at http://www.fda.gov/medwatch/getforms.htm or 
http://www.fda.gov/opacom/morechoices/fdaforms/OC.html  
 
 	  CDERs Division of Drug Information: 
 
 By e-mail:   druginfo@fda.hhs.gov 
 
 By phone: 	1-800-FDA-1088 

1-888-INFO-FDA 

1-888 463-6332 or (301) 796-3400 

 
 By mail:  Division of Drug Information 

10903 New Hampshire Avenue 

WO51-2201 

Silver Spring, MD 20993-0002 

 
2.  Generating Copies of FDA Form 3500A 
 
Copies of the form can be generated by: 
 
 	  Photocopying a blank FDA Form 3500A 
 
 	  Producing a printed facsimile of FDA Form 3500A 
 
 Generated by Fillable Forms Software at 

. 

http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/ucm149238.ht 
m  and included in Appendix 1. 
 
 Generated by commercial software that can be used after the format is agreed to in 
advance by FDA. For details see item 4 at  
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/ucm149238.ht 
m. 
 
3.  Completing FDA Form 3500A   
   
All FDA Form 3500A submissions should be legibly printed or typewritten and completed 
with a minimum font size of 8 point.  Legible photostatic copies can be submitted.  However, 
  13
 
  Contains Nonbinding Recommendations 
 
visual contrast and paper opacity should be adequate to ensure clear readable archival 
images.  A form reporting a serious adverse event associated with the use of an OTC drug 
product should have OTC Product checked in field G5 of the form.  FDA encourages 
responsible persons to use an FDA assigned national drug code (NDC) number as the product 
identifier in field C9 of the form.  The NDC number is the most useful product identifier for 
FDA.  Alternatively, if the suspect OTC drug product does not have an FDA-assigned NDC 
number, any other standard product identification code or number should be entered in field 
C9. For additional information, see Instructions on completing FDA Form 3500A at 
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/ucm149238.htm. 
 
4.  Submitting FDA Form 3500A 
 
Completed FDA Form 3500A should be sent to: 
 
Central Document Room 

Center for Drug Evaluation and Research 

Food and Drug Administration 

5901-B Ammendale Road 

Beltsville, MD 20705-1266 

 
Do not include a cover letter with the submission; all information should be included in the 
FDA Form 3500A and in attachment(s), if any. 
 
B.  Electronic Submission 
 
The AERS system is a computerized information database designed to support FDA's  
postmarketing safety surveillance program for all marketed drug and biologic products excluding 
blood components and vaccine products.  FDA has implemented the regulatory and 
infrastructure changes for full-scale implementation to accommodate electronic submissions of 
ICSRs and ICSR attachments.  
 
To fulfill the submission requirements of section 760 of the Act, responsible persons can 
complete and submit electronic ICSRs with the full outer carton/container and immediate 
container label, including the Drug Facts panel and principal display panel, as electronic ICSR 
attachments.   
 
For information on electronic submission of ICSRs and ICSR attachments, see FDAs draft 
guidance for industry entitled Providing Regulatory Submissions in Electronic Format  
Postmarketing Individual Case Safety Reports, available on the Internet at 
http://www.fda.gov/Drugs under Guidances. In addition, technical specification associated with 
the draft guidance will be provided as stand alone documents and may be updated periodically.  
To ensure that you have the most recent version of the stand alone documents, check CDERs 
guidance web page at http://www.fda.gov/cder/regulatory/ersr/#Postmarketing. 
 
 
  14
 
  Contains Nonbinding Recommendations 
 
VI.   PAPERWORK REDUCTION ACT OF 1995 
 
This guidance contains information collection provisions that are subject to review by the Office 
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 
3501-3520). 
 
The time required to complete this information collection is estimated to average of 2 hours per 
response for reporting and 5 hours per record for recordkeeping, including the time to review 
instructions, search existing data sources, gather the data needed, and complete and review the 
information collection. Send comments regarding this burden estimate or suggestions for 
reducing this burden to: 
 
  Office of Surveillance and Epidemiology  

  Center for Drug Evaluation and Research 

  Food and Drug Administration 

  10903 New Hampshire Ave. 

WO22-4316  

  Silver Spring, MD 20993-0002 

 
 
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control number. The 
 
OMB control number for this information collection is 0910-0636 (expires 06/30/2012). 
   
 
 
 
 
 
  15
 
  Contains Nonbinding Recommendations 
 
APPENDIX 1:   FDA FORM 3500A  
 
A downloadable version of FDA Form 3500A is available on the Internet at 
http://www.fda.gov/medwatch/getforms.htm.   A fillable version of the form (and instructions) is 
available at http://www.fda.gov/medwatch/safety/FDA-3500A_fillable.pdf. 
 
A copy of FDA Form 3500A is provided for reference to specific data elements discussed in this 
guidance. 
 
 
  
 
  16
 
  Form Approved: OMB No. 0910-0291, Expires: 10/31/08 
See OMB statement on reverse. 
U.S. Department of Health and Human Services  For use by user-facilities, Mfr Report # 
Food and Drug Administration  importers, distributors and manufacturers
for MANDATORY reporting  UF/Importer Report # 
MEDWATCH 

FORM FDA 3500A (10/05) 
 Page ____ of ____ 
FDA Use Only 
A. PATIENT INFORMATION  C. SUSPECT PRODUCT(S) 
1. Patient Identifier  2. Age at Time  3. Sex  4. Weight  1. Name (Give labeled strength & mfr/labeler) 
of Event: 
or  Female  lbs  #1 
or 
Date  Male  #2 
In confidence  of Birth:  kgs 
2. Dose, Frequency & Route Used  3. Therapy Dates (If unknown, give duration) 
B. ADVERSE EVENT OR PRODUCT PROBLEM  from/to (or best estimate) 
#1  #1 
1.  Adverse Event  and/or  Product Problem (e.g., defects/malfunctions) 
2. Outcomes Attributed to Adverse Event  #2  #2 
(Check all that apply)  4. Diagnosis for Use (Indication)  5. Event Abated After Use 
Death:  Disability or Permanent Damage  Stopped or Dose Reduced? 
(mm/dd/yyyy)  #1  #1  Yes  No Doesn't 
Life-threatening  Congenital Anomaly/Birth Defect  Apply 
#2 
Hospitalization -initial or prolonged  Other Serious (Important Medical Events)  6. Lot #  7. Exp. Date  #2  Yes  No  DApopelsyn 't 
Required Intervention to Prevent Permanent Impairment/Damage (Devices) 
#1  #1  8. Event Reappeared After 
3. Date of Event (mm/dd/yyyy)  4. Date of This Report (mm/dd/yyyy)  Reintroduction? 
#2  #2  #1  Yes  No  Doesn't 
Apply 
5. Describe Event or Problem  9. NDC# or Unique ID  Doesn't 
#2  Yes  No 
Apply 
10. Concomitant Medical Products and Therapy Dates (Exclude treatment of event) 
 

K
N
I
K 
C D. SUSPECT MEDICAL DEVICE 
A
1. Brand Name 
L
B
E  2. Common Device Name 
S
U
 R  3. Manufacturer Name, City and State 
O
 E 
P
Y 4. Model #  Lot #  5. Operator of Device 
T
E  Health Professional 
AS Catalog #  Expiration Date (mm/dd/yyyy)  Lay User/Patient 
E
L Serial #  Other #  Other: 
P
6. If Implanted, Give Date (mm/dd/yyyy)  7. If Explanted, Give Date (mm/dd/yyyy) 
6. Relevant Tests/Laboratory Data, Including Dates 
8. Is this a Single-use Device that was Reprocessed and Reused on a Patient? 
Yes  No 
9. If Yes to Item No. 8, Enter Name and Address of Reprocessor 
10. Device Available for Evaluation? (Do not send to FDA) 
Yes  No  Returned to Manufacturer on: 
(mm/dd/yyyy) 
11. Concomitant Medical Products and Therapy Dates (Exclude treatment of event) 
7. Other Relevant History, Including Preexisting Medical Conditions (e.g., allergies, 
race, pregnancy, smoking and alcohol use, hepatic/renal dysfunction, etc.) 
E. INITIAL REPORTER 
1. Name and Address  Phone # 
Submission of a report does not constitute an admission that medical  2. Health Professional?  3. Occupation  4. Initial Reporter Also Sent 
personnel, user facility, importer, distributor, manufacturer or product  Report to FDA 
caused or contributed to the event.  Yes  No Yes No  Unk.  FDA USE ONLY 
MEDWATCH
 
FORM FDA 3500A (10/05) (continued) 
 Page ____ of ____ 
F. FOR USE BY USER FACILITY/IMPORTER (Devices Only)  H. DEVICE MANUFACTURERS ONLY 
1. Check One  2. UF/Importer Report Number  1. Type of Reportable Event  2. If Follow-up, What Type? 
User Facility  Importer  Death  Correction 
3. User Facility or Importer Name/Address  Serious Injury  Additional Information 
Malfunction  Response to FDA Request 
Other:  Device Evaluation 
3. Device Evaluated by Manufacturer?  4. Device Manufacture Date 
(mm/yyyy) 
Not Returned to Manufacturer 
4. Contact Person  5. Phone Number  Yes  Evaluation Summary Attached 
No (Attach page to explain why not) or  5. Labeled for Single Use? 
provide code: 
6. Date User Facility or  7. Type of Report  8. Date of This Report 
Importer Became  (mm/dd/yyyy)  Yes  No 
Aware of Event (mm/dd/yyyy)  Initial 
6. Evaluation Codes (Refer to coding manual) 
Follow-up # 
9. Approximate  10. Event Problem Codes (Refer to coding manual)  Method 
Age of Device 
Patient 
Results 
Code 
Device 
Code  Conclusions 
11. Report Sent to FDA?  12. Location Where Event Occurred  7. If Remedial Action Initiated, Check Type  8. Usage of Device 
Yes  Hospital  Outpatient  Recall  Notification  Initial Use of Device 
Diagnostic Facility 
No  (mm/dd/yyyy)  Home  Ambulatory  Repair  Inspection  Reuse 
13. Report Sent to Manufacturer?  Nursing Home  Surgical Facility  Replace  Patient Monitoring  Unknown 
Yes  OFauctpiliatyti ent Treatment  Relabeling  MAdojduisfitcmaetinotn /  9. 2If1 a UctSioCn 3 r6e0pio(fr)t, elids tt oc oFrDreAc utinodne/ r 
(mm/dd/yyyy)  removal reporting number: 
No  Other:  Other: 
(Specify) 
14. Manufacturer Name/Address 
10.  Additional Manufacturer Narrative  and / or  11.  Corrected Data 
G. ALL MANUFACTURERS 
1. Contact Office -Name/Address (and Manufacturing Site  2. Phone Number 
for Devices) 
3. Report Source 
(Check all that apply) 
Foreign 
Study 
Literature 
Consumer 
Health Professional 
User Facility 
4. Date Received by  5. 
Manufacturer (mm/dd/yyyy)  (A)NDA #  Company 
Representative 
IND #  Distributor 
6. If IND, Give Protocol # 
Other: 
STN # 
PMA/ 
7. Type of Report  510(k) # 
(Check all that apply) 
Combination 
5-day  30-day  Product  Yes 
7-day  Periodic  Pre-1938  Yes
10-day  Initial 
OTC Product  Yes 
15-day  Follow-up # ____ 
9. Manufacturer Report Number  8. Adverse Event Term(s) 
The public reporting burden for this collection of information has been estimated to average 66  Department of Health and Human Services  OMB Statement: 
minutes per response, including the time for reviewing instructions, searching existing data  Food and Drug Administration -MedWatch  "An agency may not conduct or sponsor,
sources, gathering and maintaining the data needed, and completing and reviewing the  10903 New Hampshire Avenue  and a person is not required to respond 
to, a collection of information unless it 
collection of information. Send comments regarding this burden estimate or any other aspect of  Building 22, Mail Stop 4447  displays a currently valid OMB control 
this collection of information, including suggestions for reducing this burden to:  Silver Spring, MD 20993-0002  number." 
Please DO NOT RETURN this form to this address.