[Federal Register: October 15, 2007 (Volume 72, Number 198)]
[Notices]
[Page 58313-58315]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15oc07-57]
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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Draft Guidance for Industry: Questions and Answers Regarding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availability of a draft guidance entitled ``Questions and Answers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 This draft guidance is intended to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DATES: Submit written or electronic comments on the draft guidance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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Office of Nutritional Products, Labeling, and Dietary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number to which the draft guidance may be sent.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INFORMATION section for electronic access to the draft guidance.
Submit written comments on the draft guidance, including comments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
----------------------------------------------------------------------------------------------------------------
\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