Federal Register, Volume 64 Issue 19 (Friday, January 29, 1999)

[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 Burden^{1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
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 Burden^{1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
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}}