[Federal Register Volume 73, Number 179 (Monday, September 15, 2008)]
[Notices]
[Pages 53252-53254]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-21454]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2007-D-0372] (formerly Docket No. 2007D-0388)


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Adverse Event 
Reporting and Recordkeeping for Dietary Supplements as Required by the 
Dietary Supplement and Nonprescription Drug Consumer Protection Act

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by October 
15, 2008.

ADDRESSES:  To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-6974, or e-mailed to [email protected]. All comments 
should be identified with the OMB control number 0910-NEW and title, 
``Adverse Event Reporting and Recordkeeping for Dietary Supplements as 
Required by the Dietary Supplement and Nonprescription Drug Consumer 
Protection Act.'' Also include the FDA docket number found in brackets 
in the heading of this document.

FOR FURTHER INFORMATION CONTACT:  Jonna Capezzuto, Office of 
Information Management (HFA-710), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-796-3794.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Adverse Event Reporting and Recordkeeping for Dietary Supplements as 
Required by the Dietary Supplement and Nonprescription Drug Consumer 
Protection Act--(OMB Control Number 0910-NEW)

    Description of Respondents: Respondents to this collection of 
information are manufacturers, packers, and distributors of dietary 
supplements marketed in the United States.
    On December 22, 2006, the President signed into law the Dietary 
Supplement and Nonprescription Drug Consumer Protection Act (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 and recordkeeping for dietary supplements and non-
prescription drugs marketed without an approved application.
    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

[[Page 53253]]

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. Under section 761(e)(1) of the 
act, responsible persons are required to maintain records related to 
dietary supplement adverse event reports they receive, whether or not 
the adverse event is serious. These requirements became effective on 
December 22, 2007.
    As required by section 3(d)(3) of the DSNDCPA, FDA is issuing 
guidance to describe the minimum data elements for serious adverse 
event reports for dietary supplements. The 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,'' was 
issued October 15, 2007, and is consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The draft guidance discusses how, 
when, and where to submit serious 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. We are also 
providing guidance on records maintenance and access for serious and 
non-serious adverse event reports and related documents.
    In the Federal Register of October 15, 2007 (72 FR 58313), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. FDA received one comment related to the 
information collection. The comment disagreed with FDA's proposed 
estimate of the annual recordkeeping burden associated with dietary 
supplement adverse events. However, the commenter did not provide an 
alternative estimate or compelling information that the estimate 
provided by FDA was not a reasonable upper-bound estimate. Since the 
receipt of the comment, the mandatory reporting of serious adverse 
events for dietary supplements to FDA has come into effect (on December 
22, 2007). Thus, FDA now has data on mandatory dietary supplement 
adverse event reports to use in revising our reporting burden estimate. 
For the first quarter of 2008 (January 1 to April 15), FDA has received 
214 mandatory reports of serious adverse events related to dietary 
supplements. Therefore, FDA revises our annual burden estimate from 960 
mandatory reports to 856 mandatory reports of serious adverse events 
related to dietary supplements. FDA requests comments on this estimate.
    FDA estimates the burden of this collection of information as 
follows:

                                  Table 1--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                      No. of         Annual Frequency       Total Annual        Hours per
                    Respondents        per Response          Responses           Response         Total Hours
----------------------------------------------------------------------------------------------------------------
Serious adverse          71.3333                     12                856                  2              1,712
 event reports
 for dietary
 supplements
 (21 U.S.C.
 379aa-1(b)(1))
----------------------------------------------------------------------------------------------------------------
Followup                 17.83333                    12                214                  1                214
 reports of new
 medical
 information
 (21 U.S.C.
 379aa-1(c)(2))
----------------------------------------------------------------------------------------------------------------
Total                                                                                                      1,926
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    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 
limited 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 856 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 856 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 1 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

[[Page 53254]]

estimated total annual burden for followup reports of new medical 
information is shown in row 2 of table 1 of this document.
    As previously noted, 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 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. 
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. Given that we have limited 
data on how many adverse events will be reported each year to the 
responsible person, 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 over 
inclusive. 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))
----------------------------------------------------------------------------------------------------------------
\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.


    Dated: September 8, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-21454 Filed 9-12-08; 8:45 am]
BILLING CODE 4160-01-S