Guidance for Industry on Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Applications

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

[email protected]

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.
2.
3.
4.

B.

Identifiable Patient .......................................................................................................................... 7

Identifiable Reporter........................................................................................................................ 8

Suspect Drug.................................................................................................................................... 8

Serious Adverse Event.................................................................................................................... 10

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

Guidance for Industry1

Postmarketing Adverse Event Reporting for

Nonprescription Human Drug Products Marketed Without an

Approved Application

This guidance represents the Food and Drug Administration's (FDA’s) 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.
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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 109462, 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 retailer’s 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
patient’s 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., email address, phone number). When possible, the responsible person should attempt to
obtain the reporter’s 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 B’s product(s) and a copy of the label of manufacturer
A’s 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 A’s 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 A’s 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 B’s 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 patient’s 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 followup 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.
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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 FDA’s 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 drug’s 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
• CDER’s Division of Drug Information:
— By e-mail: [email protected]
— 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,
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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 FDA’s 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 CDER’s
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
Food and Drug Administration

For use by user-facilities,
importers, distributors and manufacturers
for MANDATORY reporting

MEDWATCH

A. PATIENT INFORMATION

FDA Use Only

C. SUSPECT PRODUCT(S)

2. Age at Time
of Event:

4. Weight

3. Sex

lbs

Female

or
In confidence

UF/Importer Report #

Page ____ of ____

FORM FDA 3500A (10/05)

1. Patient Identifier

Mfr Report #

or

Date
of Birth:

Male

1. Name (Give labeled strength & mfr/labeler)
#1
#2

kgs

3. Therapy Dates (If unknown, give duration)
from/to (or best estimate)

2. Dose, Frequency & Route Used

B. ADVERSE EVENT OR PRODUCT PROBLEM
1.

Adverse Event

and/or

2. Outcomes Attributed to Adverse Event
(Check all that apply)
Death:

#1

#1

#2

#2

Product Problem (e.g., defects/malfunctions)
5. Event Abated After Use
Stopped or Dose Reduced?
Doesn't
#1
Yes
No
Apply

4. Diagnosis for Use (Indication)
Disability or Permanent Damage

(mm/dd/yyyy)
Life-threatening

Congenital Anomaly/Birth Defect

Hospitalization - initial or prolonged

Other Serious (Important Medical Events)

#1
#2

#2

#1

#1

8. Event Reappeared After
Reintroduction?

#2

#2

#1

Yes

No

Doesn't
Apply

#2

Yes

No

Doesn't
Apply

Required Intervention to Prevent Permanent Impairment/Damage (Devices)
3. Date of Event (mm/dd/yyyy)

4. Date of This Report (mm/dd/yyyy)

5. Describe Event or Problem

Yes

No

Doesn't
Apply

7. Exp. Date

6. Lot #

9. NDC# or Unique ID

PLEASE TYPE OR USE BLACK INK

10. Concomitant Medical Products and Therapy Dates (Exclude treatment of event)

D. SUSPECT MEDICAL DEVICE
1. Brand Name
2. Common Device Name
3. Manufacturer Name, City and State

Lot #

4. Model #

5. Operator of Device
Health Professional

Catalog #

Expiration Date (mm/dd/yyyy)

Serial #

6. Relevant Tests/Laboratory Data, Including Dates

Other:

Other #

6. If Implanted, Give Date (mm/dd/yyyy)

Lay User/Patient

7. If Explanted, Give Date (mm/dd/yyyy)

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

Submission of a report does not constitute an admission that medical
personnel, user facility, importer, distributor, manufacturer or product
caused or contributed to the event.

Phone #

2. Health Professional? 3. Occupation
Yes

No

4. Initial Reporter Also Sent
Report to FDA
No
Unk.
Yes

FDA USE ONLY

MEDWATCH

FORM FDA 3500A (10/05) (continued)

Page ____ of ____

F. FOR USE BY USER FACILITY/IMPORTER (Devices Only)
1. Check One

2. UF/Importer Report Number

H. DEVICE MANUFACTURERS ONLY
1. Type of Reportable Event

Importer

User Facility

3. User Facility or Importer Name/Address

2. If Follow-up, What Type?

Death

Correction

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
5. Phone Number

4. Contact Person

6. Date User Facility or
Importer Became
Aware of Event (mm/dd/yyyy)

Yes

8. Date of This Report
(mm/dd/yyyy)

7. Type of Report

Yes

Method

Patient
Code

Results

Device
Code

Conclusions
12. Location Where Event Occurred

(mm/dd/yyyy)

Home
Nursing Home

13. Report Sent to Manufacturer?

Ambulatory
Surgical Facility

(mm/dd/yyyy)

Initial Use of Device

Repair

Inspection

Reuse

Replace

Patient Monitoring

Relabeling

Other:

8. Usage of Device

Notification

Recall

Outpatient Treatment
Facility

Yes
No

7. If Remedial Action Initiated, Check Type

Outpatient
Diagnostic Facility

Hospital

Yes
No

No

6. Evaluation Codes (Refer to coding manual)

10. Event Problem Codes (Refer to coding manual)

11. Report Sent to FDA?

5. Labeled for Single Use?

Initial
Follow-up #

9. Approximate
Age of Device

Evaluation Summary Attached

No (Attach page to explain why not) or
provide code:

Modification/
Adjustment

Unknown
9. If action reported to FDA under
21 USC 360i(f), list correction/
removal reporting number:

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
for Devices)

2. Phone Number

3. Report Source
(Check all that apply)
Foreign
Study
Literature
Consumer
Health Professional
4. Date Received by
Manufacturer (mm/dd/yyyy)

User Facility

5.

Company
Representative
Distributor

(A)NDA #
IND #

6. If IND, Give Protocol #

Other:

STN #
7. Type of Report
(Check all that apply)
5-day

30-day

7-day

Periodic

10-day

Initial

15-day

Follow-up # ____

9. Manufacturer Report Number

PMA/
510(k) #
Combination
Product

Yes

Pre-1938

Yes

OTC Product

Yes

8. Adverse Event Term(s)

The public reporting burden for this collection of information has been estimated to average 66
minutes per response, including the time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding this burden estimate or any other aspect of
this collection of information, including suggestions for reducing this burden to:

Department of Health and Human Services
Food and Drug Administration - MedWatch
10903 New Hampshire Avenue
Building 22, Mail Stop 4447
Silver Spring, MD 20993-0002
Please DO NOT RETURN this form to this address.

OMB Statement:
"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."