[Federal Register Volume 64, Number 19 (Friday, January 29, 1999)]
[Notices]
[Pages 4665-4667]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-2160]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 96N-0446]


Agency Information Collection Activities; Submission for OMB 
Review; Postmarketing Reporting of Adverse Drug Experiences

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 listed below 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 
March 1, 1999.
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: 
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 section 3507 of the PRA 
(44 U.S.C. 3507), FDA has submitted the following proposed collection 
of information to OMB for review and clearance.

Postmarketing Reporting of Adverse Drug Experiences--21 CFR 310.305 
and 314.80 (OMB Control Number 0910-0230--Reinstatement)

    Section 505 of the Federal Food, Drug, and Cosmetic Act (the act) 
(21 U.S.C. 355) requires applicants to submit data showing whether a 
drug is safe and effective. FDA is authorized to issue regulations 
requiring the recordkeeping and reporting necessary to enable it to 
evaluate the safety or effectiveness of a drug product, including 
whether the product is misbranded or adulterated under sections 501 and 
502 of the act (21 U.S.C. 351 and 352). Under Secs. 310.305 and 314.80 
(21 CFR 310.305 and 314.80), FDA set forth reporting and recordkeeping 
requirements regarding adverse drug experiences.
    All applicants who have received marketing approval of drug 
products are required to file Alert Reports with FDA regarding serious, 
unexpected adverse drug experiences, as well as followup reports on the 
adverse drug experiences when the applicant receives new information or 
as requested by FDA (Sec. 314.80(c)(1)). The Alert Reports include 
reports of all foreign or domestic adverse experiences, as well as 
reports obtained in scientific literature (Sec. 314.80(d)), and if 
there is a reasonable possibility that the drug caused the adverse 
experience, reports from postmarketing studies (Sec. 314.80(e)). Under 
Sec. 314.80(c)(2), applicants must provide periodic reports 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 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 on the 
adverse drug experiences when the applicant receives new information or 
as requested by FDA (Sec. 310.305(c)(1) and (c)(2)). 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 provide, for the first time, the opportunity to collect

[[Page 4666]]

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.
    Respondents to this collection of information are manufacturers, 
packers, distributors, and applicants.
    In the Federal Register of December 30, 1997 (62 FR 67874), the 
agency requested comments on the proposed collection of information. 
FDA received one comment. The comment questioned the accuracy of 
several of the information collection burden estimates, and suggested 
higher estimates for annual frequency per response and hours per 
response. In light of this comment, the agency reevaluated its 
estimates and is revising its previous estimate of the number of 
periodic reports prepared per respondent, from the 1.5 originally 
reported to 18. On review, FDA determined that this number reflects the 
average number of periodic reports it receives. A periodic report 
includes a narrative summary, individual case safety reports, and 
history of actions taken. In addition, the agency is revising the hours 
per response for preparing a periodic report under Sec. 314.80(c)(2) 
from 5 to 28 hours. The comment suggested, and FDA agrees, that 28 
hours more accurately reflects the amount of time required to prepare a 
response.
    The comment also suggested ways to enhance the quality, utility, 
and clarity of the information to be collected and ways to minimize the 
burden of the collection of information on respondents.
    FDA is in the process of revising its safety reporting and 
recordkeeping regulations and will consider these comments in 
developing its rulemaking. The respondent has had and will have an 
opportunity for comment on these rulemaking initiatives. In the Federal 
Register of October 27, 1994 (59 FR 54046), FDA published a proposed 
rule to amend its postmarketing expedited and periodic safety reporting 
requirements, as well as others, to implement international standards 
and to facilitate the reporting of adverse drug experiences. In the 
Federal Register of October 7, 1997 (62 FR 52237), FDA published a 
final rule amending its expedited safety reporting regulations to 
implement certain recommendations in the International Conference on 
Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) E2A guidance on definitions and 
standards for expedited reporting (58 FR 37408, July 9, 1993). At this 
time, the agency is further considering recommendations in the ICH E2A 
guidance for additional amendments to its postmarketing expedited 
safety reporting regulations. With respect to the proposed amendments 
to the periodic adverse drug experience reporting requirements in the 
proposal of October 27, 1994, FDA has decided to repropose these 
amendments based on recommendations in the ICH E2C guidance on periodic 
safety update reports (62 FR 27470, May 19, 1997). In developing the 
reproposal, FDA will also consider comments submitted in response to 
the proposed rule of October 27, 1994, regarding periodic adverse 
experience reports. FDA is also considering rulemaking concerning the 
electronic submission of postmarketing expedited and periodic safety 
reports using standardized medical terminology, data elements, and 
electronic transmission standards recommended by the ICH.
     FDA estimates the burden of this collection of information as 
follows:

                                  Table 1.--Estimated Annual Reporting Burden1
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                                                    Annual
        21 CFR Section              No. of       Frequency per   Total Annual      Hours per       Total Hours
                                  Respondents      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              18          12,300              28           344,400
Total                                                                                             344,406
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\1\ The reporting burden for Secs.  310.305(c)(1), (c)(2), (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 Burden1
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                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                   Recordkeepers   Recordkeeping      Records      Recordkeeper
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310.305(f)                             25               1               2               1              25
314.80(i)                             683               1             683               1             683
Total                                                                                                 708
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


[[Page 4667]]

    The numbers in Tables 1 and 2 of this document are accurate as of 
the time of publication. FDA is in the process of revising its safety 
reporting and recordkeeping regulations. These numbers may change when 
the revisions to those regulations are finalized.

    Dated: January 22, 1999.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 99-2160 Filed 1-28-99; 8:45 am]
BILLING CODE 4160-01-F