2011-94. Draft Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic.” The draft guidance discusses FDA's intended approach to enforcement of adverse event reporting requirements for drugs, biologics, medical devices, and dietary supplements during an influenza pandemic. The agency makes recommendations to industry for focusing limited resources on reports related to products indicated for the prevention and treatment of influenza and other specific types of reports indicated in the draft guidance. This draft guidance is a revision of the draft guidance for industry of the same title published on December 16, 2008.

DATES:

Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit written or electronic comments on the draft guidance by March 8, 2011. Submit written comments on the proposed collection of information by March 8, 2011.

ADDRESSES:

Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Regarding pandemic influenza: Carmen Maher, Office of Counterterrorism and Emerging Threats, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, rm. 4146, Silver Spring, MD 20993-0002, 301-796-8510.

Regarding human drug products: Solomon Iyasu, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 4447, Silver Spring, MD 20993-0002, 301-796-2370.

Regarding human biological products: Stephen Ripley, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-6210.

Regarding medical device products: Deborah Moore, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 3230, Silver Spring, MD 20993-0002, 301-796-6106.

Regarding dietary supplements: John Sheehan, Center for Food Safety and Applied Nutrition (HFS-315), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1488.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a revised draft guidance for industry entitled “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic.” In the Federal Register of December 16, 2008 (73 FR 76364), FDA published notice of the availability of a draft guidance of the same title. FDA anticipates that during an influenza pandemic, industry and FDA workforces may be reduced while reporting of adverse events related to widespread use of medical products indicated for the treatment and prevention of influenza may increase, although the extent of these possible changes is unknown. The revised draft guidance discusses FDA's intended approach to enforcement of adverse event reporting requirements for drugs, biologics, medical devices, and dietary supplements during an influenza pandemic.

II. Revisions to the 2008 Draft Guidance

FDA is issuing a revised draft guidance that includes recommendations for planning, notification, and documentation for firms that report postmarketing adverse events. The revised draft guidance recommends that each firm's pandemic influenza continuity of operations plan (COOP) include instructions for reporting adverse events and a plan for the submission of stored reports that were not submitted within regulatory timeframes. The revised draft guidance recommends that firms that are unable to fulfill normal adverse event reporting requirements during an influenza pandemic do the following:

• Document the conditions that prevent them from meeting normal reporting requirements,
• Notify the appropriate FDA organizational unit responsible for adverse event reporting compliance when these conditions exist and when the reporting process is restored, and
• Maintain records to identify what reports have been stored.

These recommendations represent collections of information under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520) discussed in section IV of this document. In issuing this revised draft guidance, FDA considered all comments that were submitted in response to the December 2008 draft guidance. Most comments requested that greater clarity be provided in certain sections; FDA has revised these sections accordingly.

This draft guidance does not address monitoring and reporting of adverse events that might be imposed as a condition of authorization for products authorized for emergency use under section 564 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360bbb-3). This draft guidance also does not address monitoring and reporting of adverse events as required by regulations establishing the conditions for investigational use of drugs, biologics, and devices. (See 21 CFR parts 312 and 812.)

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the Agency's current thinking on postmarketing adverse event reporting for medical products and dietary supplements during pandemic influenza. 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.

III. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) either electronic or written comments regarding this document. It is only necessary to send one set of comments. It is no longer necessary to send two copies of mailed comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

IV. Paperwork Reduction Act of 1995

Under the PRA, Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information that they conduct or sponsor. “Collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA, 44 U.S.C. 3506(c)(2)(A), requires Federal agencies to provide a 60-day notice in the Federal Register for each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing this notice of the proposed collection of information set forth in this document.

With respect to the collection of information associated with this draft guidance, FDA invites comments on the following topics: (1) Whether the proposed information collected is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimated burden of the proposed information collected, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information collected; and (4) ways to minimize the burden of information collected on the respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

The draft guidance explains FDA's approach to enforcement of adverse event reporting requirements for drugs, biologics, medical devices, and dietary supplements during an influenza pandemic, including an intent not to object to changes in the timing of submission of certain reports during some stages of the pandemic response. The Agency recommends that each firm's pandemic influenza COOP include instructions for reporting adverse events, including a plan for the submission of stored reports that were not submitted within regulatory timeframes. The draft guidance explains that firms that are unable to fulfill normal adverse event reporting requirements during an influenza pandemic should: (1) Maintain documentation of the conditions that prevent them from meeting normal reporting requirements, (2) notify the appropriate FDA organizational unit responsible for adverse event reporting compliance when the conditions exist and when the reporting process is restored, and (3) maintain records to identify what reports have been stored.

Based on the number of manufacturers that would be covered by the draft guidance, we estimate that approximately 5,000 firms will add to their COOP: (1) Instructions for reporting adverse events and (2) a plan for submitting stored reports that were not submitted within regulatory timeframes. We estimate that each firm will take approximately 50 hours to prepare the adverse event reporting plan for its COOP.

We estimate that approximately 500 firms will be unable to fulfill normal adverse event reporting requirements because of conditions caused by an influenza pandemic and that these firms will notify the appropriate FDA organizational unit responsible for adverse event reporting compliance when the conditions exist. Although we do not anticipate such pandemic influenza conditions to occur every year, for purposes of the PRA, we estimate that each of these firms will notify FDA approximately once each year, and that each notification will take approximately 8 hours to prepare and submit.

Concerning the recommendation in the draft guidance that firms unable to fulfill normal adverse event reporting requirements maintain documentation of the conditions that prevent them from meeting these requirements and also maintain records to identify what adverse event reports have been stored and when the reporting process is restored, we estimate that approximately 500 firms will each need approximately 8 hours to maintain the documentation and that approximately 500 firms will each need approximately 8 hours to maintain the records. Therefore, the total recordkeeping burden that would result from the draft guidance would be 258,000 hours.

The draft guidance also refers to previously approved collections of information found in FDA's adverse event reporting requirements in 21 CFR 310.305, 314.80, 314.98, 600.80, 606.170, 640.73, 1271.350, and part 803. These regulations contain collections of information 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) and are approved under OMB control numbers 0910-0116, 0910-0291, 0910-0230, 0910-0308, 0910-0437, and 0910-0543. In addition, the draft guidance also refers to adverse event reports for nonprescription human drug products marketed without an approved application and dietary supplements required under sections 760 and 761 of the FD&C Act (21 U.S.C. 379aa and 379aa-1), which include collections of information approved under OMB control numbers 0910-0636 and 0910-0635.

FDA estimates the burden of this collection of information as follows:

Table 1—Estimated Annual Reporting Burden ¹

	Number of respondents	Number of responses per respondent	Total responses	Hours per response	Total hours
Notify FDA when normal reporting is not feasible	500	1	500	8	4,000
Total					4,000
1 There are no capital costs or operating and maintenance costs associated with this information collection.

Table 2—Estimated Recordkeeping Burden ¹

	Number of recordkeepers	Number of records per recordkeeping	Total records	Hours per record	Total hours
Add adverse event reporting plan to COOP	5,000	1	5,000	50	250,000
Maintain documentation of influenza pandemic conditions and resultant high absenteeism	500	1	500	8	4,000
Maintain records to identify what reports have been stored and when the reporting process was restored	500	1	500	8	4,000
Total					258,000
1 There are no capital costs or operating and maintenance costs associated with this information collection.

V. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm,, http://www.fda.gov/​BiologicsBloodVaccines/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm,, http://www.fda.gov/​MedicalDevices/​DeviceRegulationandGuidance/​GuidanceDocuments/​default.htm,, http://www.fda.gov/​Food/​GuidanceComplianceRegulatoryInformation/​GuidanceDocuments/​default.htm,, or http://www.regulations.gov.

Dated: January 3, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.