[Federal Register Volume 67, Number 140 (Monday, July 22, 2002)]
[Notices]
[Pages 47821-47823]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-18462]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02N-0012]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; Postmarketing Adverse Drug Experience 
Reporting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
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 (the PRA).

DATES: Submit written comments on the collection of information by 
August 21, 2002.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Stuart Shapiro, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information 
Resources Management (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1482.

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.

[[Page 47822]]

Postmarketing Adverse Drug Experience Reporting--21 CFR 310.305 and 
314.80 (OMB Control Number 0910-0230)--Extension

    Sections 201, 502, 505, and 701 of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 321, 352, 355, and 371) require that 
marketed drugs be safe and effective. In order to know whether drugs 
that are not safe and effective are on the market, FDA must be promptly 
informed of adverse experiences occasioned by the use of marketed 
drugs. In order to help ensure this, FDA issued regulations 
(Secs. 310.305 and 314.80 (21 CFR 310.305 and 314.80)) to impose 
reporting and recordkeeping requirements on the drug industry that 
would enable FDA to take action necessary for protection of the public 
health from adverse drug experiences.
    All applicants who have received marketing approval of drug 
products are required to report to FDA serious, unexpected adverse drug 
experiences, as well as followup reports when needed 
(Sec. 314.80(c)(1)). This includes reports of all foreign or domestic 
adverse experiences as well as those obtained in scientific literature 
and from postmarketing epidemiological/surveillance studies. Under 
Sec. 314.80(c)(2) applicants must provide periodic reports of adverse 
drug experiences. A periodic report includes, for the reporting 
interval, reports of serious, expected adverse drug experiences and all 
nonserious adverse drug experiences, a narrative summary and analysis 
of adverse drug experiences and a history of actions taken because of 
adverse drug experiences. Under Sec. 314.80(i) applicants must keep for 
10 years records of all adverse drug experience reports known to the 
applicant.
    For marketed prescription drug products without approved new drug 
applications (NDAs) or abbreviated new drug applications, 
manufacturers, packers, and distributors are required to report to FDA 
serious, unexpected adverse drug experiences as well as followup 
reports when needed (Sec. 310.305(c)). Under Sec. 310.305(f) each 
manufacturer, packer, and distributor shall maintain for 10 years 
records of all adverse drug experiences required to be reported.
    The primary purpose of FDA's adverse drug experience reporting 
system is to provide a signal for potentially serious safety problems 
with marketed drugs. Although premarket testing discloses a general 
safety profile of a new drug's comparatively common adverse effects, 
the larger and more diverse patient populations exposed to the marketed 
drug provides, for the first time, the opportunity to collect 
information on rare, latent, and long-term effects. Signals are 
obtained from a variety of sources, including reports from patients, 
treating physicians, foreign regulatory agencies, and clinical 
investigators. Information derived from the adverse drug experience 
reporting system contributes directly to increased public health 
protection because the information enables FDA to make important 
changes to the product's labeling (such as adding a new warning) and 
when necessary, to initiate removal of a drug from the market.
    In the Federal Register of February 25, 2002 (67 FR 8545), the 
agency requested comments on the proposed collection of information. 
FDA received two comments.
    The comments asked what methodology and assumptions were used by 
FDA to calculate the burden estimates.
    The ``hours per response'' were based on FDA's estimates of the 
time it would take manufacturers, packers, distributors, and applicants 
of marketed human drug products to submit the information to the 
agency.
    The comments said that the annual number of responses of periodic 
reports is significantly underestimated. One comment estimated that 
companies submit more than 400 periodic reports (annual and quarterly 
reports) annually. The other comment estimated that it submits over 70 
periodic reports annually.
    FDA data indicates that it receives, on average, approximately 
10,245 periodic reports (annual and quarterly reports) annually. A 
periodic report includes, as previously indicated, a narrative summary, 
individual case safety reports, and history of actions taken. Although 
some companies may submit 400 periodic reports annually, others only 
submit 1 periodic report annually.
    The comments stated that the burden estimate seems to reflect only 
FDA's effort and not that of the respondents. The comments said that 
the hours per response for preparing periodic reports is grossly 
underestimated. One comment said that the preparation, quality control, 
and duplication of NDA periodic reports takes, on average, from 16 to 
40 hours each, while the other comment said that this processing takes 
from 100 to 300 hours for each periodic report. The comments said that 
all adverse experience reports, including the non-15-day alert reports, 
need to be taken into account when calculating the burden, because all 
need to be reviewed, assessed, and processed for determination of 
``expedited'' status and for inclusion in the periodic safety update 
reports. For example, the comments said that one company received 
approximately 49,000 initial adverse drug experience reports in 
association with their marketed prescription products from worldwide 
sources in 2001, approximately 4,800 of which qualified as 15-day alert 
reports; this included both initial and followup reports. Another 
company received approximately 20,000 initial adverse event reports 
from worldwide sources in 2001, approximately 2,000 of which qualified 
as 15-day alert reports; this included both initial and followup 
reports.
    FDA notes that the estimate of 5 hours in the Federal Register of 
February 25, 2002, document was a typographical error. The correct 
estimate should be 28 hours. As explained in the information collection 
notice that published in the Federal Register of January 29, 1999 (64 
FR 4665), this estimate is based on industry suggestions.
    The comments questioned whether there are no capital, operating, or 
maintenance costs associated with maintaining records of adverse 
experience reports for 10 years. The comments said that companies must 
maintain facilities to store paper records in addition to backup 
records on other media. Costs for storage and retrieval vary widely, 
depending on the volume of records, rental fees, transportation costs, 
and retrieval fees, but may be substantial (i.e., thousands of dollars 
annually).
    FDA agrees that there are maintenance costs associated with 
maintaining records of adverse experience reports for 10 years. FDA 
estimates that these costs are approximately $2,000 per company 
annually, as suggested by the comments.
    The comments also provided several suggestions on how the 
regulations should be revised to enhance the reporting efficiency and 
to minimize the burden of the collection of information. For example, 
the comments said that FDA should revise the requirements to be 
consistent with the International Conference on Harmonization (ICH) 
guidelines for periodic safety update reports.
    FDA is in the process of revising its safety reporting and 
recordkeeping regulations and will consider these comments in 
finalizing its rulemaking. Respondents will have an opportunity to 
comment further on these rulemaking initiatives. As stated in the 
Federal Register of May 13, 2002 (67 FR 33059), FDA is planning to 
publish a proposed rule that would amend the expedited and periodic 
safety reporting regulations

[[Page 47823]]

for human drugs and biologics to revise certain definitions and 
reporting formats as recommended by the ICH and to define new terms; to 
possibly add to or revise current reporting requirements; to consider 
revising certain reporting timeframes; and to suggest other revisions 
to these regulations to enhance the quality of safety reports received 
by FDA.
    Respondents to this collection of information are manufacturers, 
packers, distributors, and applicants. FDA estimates the burden of this 
collection of information as follows:

             Table 1.--Estimated Annual Reporting Burden\1\
------------------------------------------------------------------------
                                    Annual
                        No. of    Frequency    Total      Hours    Total
   21 CFR Section    Respondents     per       Annual      per     Hours
                                   Response  Responses  Response
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310.305(c)(5)               1           1          1         1        1
314.80(c)(1)(iii)           5           1          5         1        5
314.80(c)(2)              683          15     10,245        28    286,86
                                                                      0
Total                                                             286,86
                                                                      6
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\1\The reporting burden for Secs.  310.305(c)(1), (c)(2), and (c)(3),
  and 314.80(c)(1)(i) and (c)(1)(ii) was reported under OMB control
  number 0910-0291. There are no capital costs or operating and
  maintenance costs associated with this collection of information.


                               Table 2.--Estimated Annual Recordkeeping Burden\1\
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 21 CFR                         Annual Frequency       Total Annual          Hours per
Section  No of Recordkeepers   per Recordkeeping         Records            Recordkeeper         Total Hours
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310.305              25                    1                   25                    1                   25
 (f)
314.80(             683                    1                  683                    1                  683
 i)
Total                                                                                                   708
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\1\There are no capital costs or operating costs associated with this collection of information. There are
  maintenance costs of $2,000 annually.

    These estimates are based on FDA's knowledge of adverse drug 
experience reporting, including knowledge about the time needed to 
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prepare the reports and the number of reports submitted to the agency.

    Dated: July 15, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-18462 Filed 7-19-02; 8:45 am]
BILLING CODE 4160-01-S