[Federal Register Volume 72, Number 198 (Monday, October 15, 2007)]
[Notices]
[Pages 58313-58315]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 07-5074]



[[Page 58313]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007D-0388]


Draft Guidance for Industry: Questions and Answers Regarding 
Adverse Event Reporting and Recordkeeping for Dietary Supplements as 
Required by the Dietary Supplement and Nonprescription Drug Consumer 
Protection Act; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance entitled ``Questions and Answers 
Regarding Adverse Event Reporting and Recordkeeping for Dietary 
Supplements as Required by the Dietary Supplement and Nonprescription 
Drug Consumer Protection Act.'' This draft guidance is intended to 
assist the dietary supplement industry in complying with the serious 
adverse events reporting and recordkeeping requirements prescribed for 
dietary supplement manufacturers, packers, and distributors by the 
Dietary Supplement and Nonprescription Drug Consumer Protection Act. 
Separate guidance, issued by the Center for Drug Evaluation and 
Research on reporting for nonprescription (over-the-counter (OTC)) 
human drugs marketed without an approved application, is announced 
elsewhere in this issue of the Federal Register.

DATES: Submit written or electronic comments on the draft guidance 
document, including comments regarding proposed collection of 
information, by December 14, 2007.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Office of Nutritional Products, Labeling, and Dietary 
Supplements (HFS-800), Food and Drug Administration, 5100 Paint Branch 
Pkwy., College Park, MD 20740. Send one self-addressed adhesive label 
to assist the office in processing your request, or include a fax 
number to which the draft guidance may be sent. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance.
    Submit written comments on the draft guidance, including comments 
regarding proposed collection of information, to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments 
to either http://www.fda.gov/dockets/ecomments or http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Vasilios Frankos, Center for Food 
Safety and Applied Nutrition (HFS-810), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-2375.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance entitled 
``Questions and Answers Regarding Adverse Event Reporting and 
Recordkeeping for Dietary Supplements as Required by the Dietary 
Supplement and Nonprescription Drug Consumer Protection Act.'' On 
December 22, 2006, the President signed into law the Dietary Supplement 
and Nonprescription Drug Consumer Protection Act (the DSNDCPA) (Public 
Law 109-462, 120 Stat. 3469). This law amends the Federal Food, Drug, 
and Cosmetic Act (the act) with respect to serious adverse event 
reporting for dietary supplements and non-prescription drugs marketed 
without an approved application. The draft guidance document contains 
questions and answers relating to the new requirements under the 
DSNDCPA, concerning the mandatory reporting to FDA of serious adverse 
events associated with dietary supplements, the minimum data elements 
to be submitted in such reports, and records of serious and non-serious 
adverse events reported to a dietary supplement manufacturer, packer, 
or distributor.
    The draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent 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 requirement of the applicable statutes 
and regulations.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information 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 concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information set forth below.
    With respect to the following collection of information, FDA 
invites comment on: (1) Whether the proposed collection of information 
is necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection on respondents, including through the use of automated 
collection techniques, when appropriate, and other forms of information 
technology.
    Title: Adverse Event Reporting and Recordkeeping for Dietary 
Supplements as Required by the Dietary Supplement and Nonprescription 
Drug Consumer Protection Act.
    Description of Respondents: Respondents to this collection of 
information are manufacturers, packers, and distributors of dietary 
supplements marketed in the United States.
    The draft guidance presents FDA's recommendations for complying 
with the dietary supplement adverse event reporting and recordkeeping 
requirements of the act, as amended by the DSNDCPA. These requirements 
become effective on December 22, 2007.

A. Reporting

    Under section 761(b)(1) of the act (21 U.S.C. 379aa-1(b)(1)), the 
manufacturer, packer, or distributor whose name (under section 
403(e)(1) of the act (21 U.S.C. 343(e)(1))) appears on the label of a 
dietary supplement marketed in the United States is required to submit 
to FDA any serious adverse event report it receives regarding use of 
the dietary supplement in the United States, accompanied by a copy of 
the product label. In addition, under section 761(c)(2) of the act, the 
submitter of the serious adverse event report (referred to in the 
statute as the ``responsible person'') is required to submit to FDA a 
followup report of any related new medical information the responsible 
person receives within 1 year of the initial report.
    The draft guidance discusses how, when, and where to submit serious

[[Page 58314]]

adverse event reports for dietary supplements and followup reports of 
new medical information. In accordance with the statutory requirements 
that serious adverse event reports for dietary supplements be submitted 
via MedWatch (section 761(d) of the act) and that FDA consolidate all 
information related to a serious adverse event into a single report 
(section 761(c)(3) of the act), the draft guidance directs the 
responsible person to submit serious adverse event reports on MedWatch 
Form 3500A and to attach a copy of the initial serious adverse event 
report on Form 3500A as part of any followup report of new medical 
information.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                         No. of        Annual frequency     Total annual        Hours per
                      respondents        per response        responses           response         Total hours
----------------------------------------------------------------------------------------------------------------
Serious adverse                   80                 12                960                  2              1,920
 event reports
 for dietary
 supplements (21
 U.S.C. 379aa-
 1(b)(1))
----------------------------------------------------------------------------------------------------------------
Followup reports                  20                 12                240                  1                420
 of new medical
 information (21
 U.S.C. 379aa-
 1(c)(2))
----------------------------------------------------------------------------------------------------------------
Total                                                                                                      2,160
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

B. Reporting Burden

    Because mandatory reporting of serious adverse events for dietary 
supplements does not become effective until December 22, 2007, FDA has 
no data on mandatory dietary supplement adverse event reports from past 
years to use in developing a burden estimate. However, FDA currently 
collects voluntarily-submitted adverse event reports for dietary 
supplements. Industry, health care providers, and consumers voluntarily 
submit several thousand reports annually to FDA's Center for Food 
Safety and Applied Nutrition (CFSAN) through the CFSAN Adverse Events 
Reporting System (CAERS), which contains reports of adverse events 
associated with conventional foods, dietary supplements, and cosmetics. 
According to a Congressional Budget Office Cost Estimate (Ref. 1), in 
2005 CAERS received almost 500 reports of adverse events suspected to 
be related to dietary supplements.
    Only manufacturers, packers, and distributors of dietary 
supplements are required to report adverse events for these products to 
FDA, and only if the firm's name appears on the label of the dietary 
supplement associated with the adverse event. Moreover, reporting is 
required only for those adverse events defined as ``serious.'' FDA does 
not know how many of the 500 reports of dietary supplement adverse 
events voluntarily submitted in 2005 would have been considered 
serious, nor how many of these reports originated from or were reported 
to the manufacturer, packer, or distributor whose name appears on the 
label of the dietary supplement associated with the adverse event. As a 
rough estimate for planning purposes, CAERS staff estimate that they 
will receive about 80 serious adverse event reports relating to dietary 
supplements each month. Thus, we estimate that the number of dietary 
supplement serious adverse event reports submitted to FDA annually will 
total 960 reports (12 x 80 reports per month). FDA requests comments on 
this estimate.
    FDA's Center for Drug Evaluation and Research estimates it will 
take respondents a total of 2 hours to collect information about a 
serious adverse event associated with an over-the-counter drug marketed 
without an approved application and report the information to FDA on 
MedWatch Form 3500A. That time burden estimate is based on FDA's 
knowledge of the adverse drug experience reports submitted to the 
agency for nonprescription drug products marketed under an approved 
application, including knowledge about the time needed to prepare the 
reports. FDA believes that the time for a dietary supplement firm to 
collect information about a serious adverse event associated with a 
dietary supplement and report the information to FDA will be 
approximately the same, as MedWatch Form 3500A will be used in both 
cases; therefore, we also estimate this time burden at 2 hours per 
report. The estimated total annual burden for dietary supplement 
serious adverse event reports is shown in row 1 of table 1 of this 
document.
    If a firm that has submitted a serious adverse event report 
receives new medical information related to the serious adverse event 
within 1 year of submitting the initial report, the firm must provide 
the new medical information to FDA in a followup report. Given our lack 
of experience with mandatory dietary supplement adverse event 
reporting, we do not have any information on the number of followup 
reports of new medical information that will be submitted to FDA each 
year. We expect followup medical information to be reported for some 
percentage of the 960 serious adverse event reports we estimate 
receiving annually. In the absence of data that would support a more 
precise estimate, we will assume that 25 percent of the 960 serious 
adverse event reports for dietary supplements will have a followup 
report submitted. FDA requests comments on this estimate. We estimate 
that each followup report will require an hour to assemble and submit, 
including the time needed to copy and attach the initial serious 
adverse event report as recommended in the draft guidance. We assume 
the followup report will take less time than the initial serious 
adverse event report, as the responsible person will not need to fill 
out Form 3500A for the followup report. FDA requests comments on 
whether the burden estimate of 1 hour is reasonable for this 
information collection. The estimated total annual burden for followup 
reports of new medical information is shown in row 2 of table 1 of this 
document.

C. Recordkeeping

    Section 761(e)(1) of the act requires that responsible persons 
maintain records related to dietary supplement adverse event reports 
they receive, whether or not the adverse event is serious. Under the 
statute, the records must be retained for a period of 6 years. The 
draft guidance provides FDA's recommendations as to what records

[[Page 58315]]

industry should maintain to satisfy the statutory recordkeeping 
requirement.
    The guidance recommends that the responsible person document its 
attempts to obtain the minimum data elements for a serious adverse 
event report. Along with these records, the guidance recommends that 
the responsible person keep the following other records: (1) 
Communications between the responsible person and the initial reporter 
of the adverse event and with any other person(s) who provided 
information about the adverse event; (2) (for serious adverse events 
only) the responsible person's serious adverse event report to FDA on 
MedWatch Form 3500A, with attachments; (3) any new medical information 
about the adverse event received by the responsible person; (4) (for 
serious adverse events only) any reports to FDA of new medical 
information related to the serious adverse event report. We estimate 
that assembling and filing these records, including any necessary 
photocopying, will take approximately 0.5 hours per adverse event 
report received by the responsible person.
    Once the documents pertaining to an adverse event report have been 
assembled and filed, FDA expects the records retention burden to be 
minimal, as the agency believes most establishments would normally keep 
this kind of record for at least several years after receiving the 
report, as a matter of usual and customary business practice. FDA 
requests comment on current adverse event recordkeeping practices in 
the dietary supplement industry, including the length of time such 
records are typically kept.
    According to a 2001 report by the Office of the Inspector General, 
between 1994-1999 FDA received 2,547 adverse event reports involving 
dietary supplements, or about 500 reports per year, on average (Ref. 
2). According to the report, the actual number of adverse events 
relating to dietary supplements is likely to be at least 100 times that 
many, or more than 50,000 adverse events per year. In the absence of 
data on how many adverse events will be reported each year to the 
responsible person once the DSNDCPA becomes effective in December 1997, 
we are using the 50,000 per year figure as an upper bound estimate of 
reporting. This is almost certainly an overestimate of the number of 
reports the firms will receive, as it is unlikely that every adverse 
event that occurs will be reported to the responsible person. FDA 
requests comments on this estimate.
    We estimated in the economic impact analysis of the Dietary 
Supplement Good Manufacturing Practices final rule (the GMP final rule) 
(72 FR 34752, June 25, 2007) that there are 1,460 manufacturers, 
packers, and holders of dietary supplements (72 FR 34752 at 34920). We 
assume that the estimated 50,000 adverse event reports related to 
dietary supplements will be spread evenly among these firms. The 
estimate of the number of manufacturers, packers, and holders of 
dietary supplements from the GMP final rule is FDA's best estimate of 
the number of firms that are ``responsible persons'' who must comply 
with the recordkeeping requirements of the DSNDCPA; however, it is not 
a precise estimate because the number of dietary supplement 
establishments covered by the GMP final rule is likely to be larger 
than the number of ``responsible persons,'' where a ``responsible 
person'' is a dietary supplement manufacturer, packer, or distributor 
whose name is listed on the label of a dietary supplement marketed in 
the United States (see section 761(b)(1) of the act). Thus, FDA's 
estimate for the number of respondents in table 2 may be overinclusive. 
FDA requests comments on the number of firms that would be subject to 
the recordkeeping requirements of the DSNDCPA.
    The estimated total annual recordkeeping burden under the statute 
and this guidance is shown in table 2 of this document.

                               Table 2.--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                         No. of        Annual frequency     Total annual
                     recordkeepers    per recordkeeping     records \2\     Hours per  record     Total hours
----------------------------------------------------------------------------------------------------------------
Dietary                        1,460             4.2465             50,000                0.5             25,000
 supplement
 adverse event
 records (21
 U.S.C. 379aa-
 1(e)(1))
----------------------------------------------------------------------------------------------------------------
Total                                                                                                     25,000
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ For purposes of estimating the number of records and hours per record, a ``record'' means all records kept
  for an individual adverse event report received by the responsible person.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the draft 
guidance, including comments regarding proposed collection of 
information. Submit a single copy of electronic comments or two paper 
copies of any mailed comments, except that individuals may submit one 
paper copy. Comments are to be identified with the docket number found 
in brackets in the heading of this document. The draft guidance and 
received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.

IV. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. S. 3546 Dietary Supplement and Nonprescription Drug and 
Consumer Protection Act, Congressional Budget Office Cost Estimate, 
December 27, 2006.
    2. ``Adverse Event Reporting For Dietary Supplements: An 
Inadequate Safety Valve,'' Office of the Inspector General, 
Department of Health and Human Services, April 2001, OEI-01-00-
00180.

V. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
at http://www.cfsan.fda.gov/guidance.html.

    Dated: October 10, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 07-5074 Filed 10-11-07; 11:34 am]
BILLING CODE 4160-01-S