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

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