Reporting Guidance

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)

XXXX 2008

OTC

Guidance for Industry

Postmarketing Adverse Event

Reporting for Nonprescription

Human Drug Products Marketed

Without an Approved Application

Additional copies are available from

:

Office of Training and 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)

XXXX 2008

OTC

TABLE OF CONTENTS

I. INTRODUCTION 1

II. BACKGROUND 1

III. MINIMUM DATA ELEMENTS FOR AN INDIVIDUAL CASE SAFETY REPORT (ICSR) 3

A. Initial ICSR Submission 3

1. Identifiable Patient 4

2. Identifiable Reporter 5

3. Suspect Drug 5

4. Serious Adverse Event 6

B. Submission of New Medical Information (Follow-up Reports) 8

IV. SUBMITTING THE LABEL 9

V. REPORTING FORMATS for paper or electronic submissions 9

A. Paper Submission (FDA Form 3500A) 9

1. Acquiring Copies of FDA Form 3500A 9

2. Generating Copies of FDA Form 3500A 10

3. Completing FDA Form 3500A 10

4. Submitting FDA Form 3500A 11

B. Electronic Submission 11

Appendix 1: FDA Form 3500A 12

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 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 (21 U.S.C. 355) 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

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 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. 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.

The responsible person should actively seek follow-up information for the purposes of completing all the applicable elements for an ICSR. The responsible person should document its efforts to obtain additional relevant information. If the responsible person documents these efforts, then the responsible person must maintain the documentation for 6 years and allow FDA to access the records (section 760(e) of the Act).

1. Identifiable Patient

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. To meet the minimum requirement for an identifiable reporter, the responsible person should obtain sufficient information to indicate the existence of a specific person who purports to have actual knowledge about the patient, adverse event and drug involved. One or more of the following automatically qualifies a reporter as identifiable: a personal identifier (e.g., name), professional identifier (e.g., health profession), or contact information (e.g., e-mail address, phone number).

Individual judgment will be needed at times to decide whether or not a reporter should be considered identifiable for reporting purposes. Care should be taken to avoid submission of reports based on rumor (e.g., “my neighbor told me that a friend of his heard…”). The responsible person should attempt to obtain sufficient information for the responsible person to follow-up, such as a phone number or e-mail address of the responsible person.

If the reporter requests that the responsible person not forward their contact information to FDA, the responsible person can submit a report without specific identification of the reporter provided that the responsible person maintains the contact information so that the responsible person can contact the reporter either upon request by FDA or on its own initiative. For these reports, the responsible person should fill in the reporter identity fields in an ICSR with a statement such as “Requested Anonymity.”

3. Suspect Drug

To meet the minimum requirement for a suspect drug, the responsible person should have information on the active ingredient(s) used by the patient (e.g., acetaminophen and phenylephrine hydrochloride). The minimum requirement for a suspect drug has not been met if the reporter cannot provide sufficient information for the responsible person to ascertain the active ingredient(s) used by the patient. 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.

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 one copy of the same 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) should 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). In such a case, manufacturer A should send manufacturer B a copy of the submitted FDA Form 3500A, including manufacturer A’s report number. In this case, manufacturer B should 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).

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 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, unless the ICSR has already been submitted to FDA by the first responsible person (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.

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 labels submitted with the report should include a representative copy of the current full outer carton/container label and immediate container label, including the Drug Facts panel and the principal display panel. 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.

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: druginfo@fda.hhs.gov

— By phone: 1-888-INFO-FDA
1-888 463-6332 or (301) 827-4570

— By mail: Division of Drug Information
5600 Fishers Lane, HFD-240
Rockville, MD 20857

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/medwatch/safety/FDA-3500A_Fillable_08-16-2006.pdf 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/medwatch/report/instruc_10-13-06.htm#obtain.

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, 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/medwatch/report/instruc_10-13-06.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/cder/guidance/5161dft.pdf. 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.

Appendix 1: FDA Form 3500A

A downloadable version of FDA Form 3500A is available on the Internet at http://www.fda.gov/medwatch/SAFETY/3500A.pdf. 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.

[Insert PDF version of Form FDA 3500A here]

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/cder/regulatory/default.htm#Legislation (http://www.fda.gov/cder/regulatory/public_law_109462.pdf).

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, those not yet subject to a final monograph, and those marketed outside the monograph system. 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 its safety reporting obligations under the Act. If the retailer enters into such an agreement and the retailer complies with its obligation to forward the adverse event reports it receives to the other party (i.e., the manufacturer or packer), the retailer need not report to FDA any serious adverse events forwarded to the manufacturer or packer under the agreement.

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 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/cder/guidance/index.htm. 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.gda.gov/cder/guidance/index.htm.

9 See the guidance for industry on Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment, available at http://www.fda.gov/cder/guidance/index.htm.

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).