Agency Information Collection Activities: Proposed Collection; Comment Request

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0482]

Agency Information Collection Activities: Proposed Collection;

Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an

opportunity for public comment on the proposed collection of certain

information by the agency. Under the Paperwork Reduction Act of 1995

(the PRA), Federal agencies are required to publish notice in the

Federal Register concerning each proposed collection of information,

including each proposed extension of an existing collection of

information, and to allow 60 days for public comment in response to the

notice. This notice solicits comments on information collection

provisions relating to the regulation of FDA's adverse experience

reporting (AER) for licensed biological products and general records.

DATES: Submit written comments on the collections of information by

September 8, 1998.

ADDRESSES: Submit written comments on the collections of information to

the Dockets Management Branch (HFA-305), Food and Drug Administration,

5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should

be identified with the docket number found in brackets in the heading

of this document.

FOR FURTHER INFORMATION CONTACT: Jonnalynn P. Capezzuto, Office of

Information Resources Management (HFA-250), Food and Drug

Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal

agencies must obtain approval from the Office of Management and Budget

(OMB) for each collection of information they conduct or sponsor.

``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR

1320.3(c) and includes agency requests or requirements that members of

the public submit reports, keep records, or provide information to a

third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c

)(2)(A)) requires Federal agencies to provide a 60-day notice in the

Federal Register concerning each proposed collection of information

before submitting the collection to OMB for approval. To comply with

this requirement, FDA is publishing notice of the proposed collections

of information listed below.

With respect to the following collection of information, FDA

invites comments on: (1) Whether the proposed collection of information

is necessary for the proper performance of FDA's functions, including

whether the information will have practical utility; (2) the accuracy

of FDA's estimate of the burden of the proposed collection of

information, including the validity of the methodology and assumptions

used; (3) ways to enhance the quality, utility, and clarity of the

information to be collected; and (4) ways to minimize the burden of the

collection of information on respondents, including through the use of

automated collection techniques, when appropriate, and other forms of

information technology.

Adverse Experience Reporting for Licensed Biological Products--21

CFR 600.80, 600.81, and 600.90; and General Records--21 CFR 600.12

(OMB Control Number 0910-0308)--Extension

Under the Public Health Service Act (42 U.S.C. 262), FDA is

required to ensure the marketing of only those biological products that

are safe and effective. FDA must therefore be informed of all adverse

experiences occasioned by the use of licensed biological products. FDA

issued the adverse experience reporting requirements to enable FDA to

take actions necessary for the protection of the public health in

response to reports of adverse experiences related to licensed

biological products. The primary purpose of FDA's adverse experience

reporting system is to flag potentially serious safety problems with

licensed biological products, focusing especially on newly licensed

products. 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 licensed biological

product provides the opportunity to collect information on rare,

latent, and long-term effects. Reports are obtained from a variety of

sources, including patients, physicians, foreign regulatory agencies,

and clinical investigators. Information derived from

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the adverse experience reporting system contributes directly to

increased public health protection because such information enables FDA

to recommend important changes to the product's labeling (such as

adding a new warning), to initiate removal of a biological product from

the market when necessary, and to assure the manufacturer has taken

adequate corrective action if necessary.

Manufacturers of biological products for human use must also keep

records of each step in the manufacture and distribution of products

including any recalls of the product. The recordkeeping requirements

serve preventative and remedial purposes. These requirements establish

accountability and traceability in the manufacture and distribution of

products, and enable FDA to perform meaningful inspections.

Section 600.12 (21 CFR 600.12) requires that all records of each

step in the manufacture and distribution of a product be made and

retained for no less than 5 years after the records of manufacture have

been completed or 6 months after the latest expiration date for the

individual product, whichever represents a later date. In addition,

records of sterilization of equipment and supplies, animal necropsy

records, and records in cases of divided manufacturing of a product are

required to be maintained. Section 600.12(b)(2) requires complete

records to be maintained pertaining to the recall from distribution of

any product.

Section 600.80(c)(1) (21 CFR 600.80(c)(1)) requires the licensed

manufacturer to report each adverse experience that is both serious and

unexpected, regardless of source, as soon as possible but in any case

within 15 working days of initial receipt of the information. Section

600.80(e) requires licensed manufacturers to submit a 15-day alert

report obtained from a postmarketing clinical study only if there is a

reasonable possibility that the product caused the adverse experience.

Section 600.80(c)(2) requires the licensed manufacturer to report each

adverse experience not reported under paragraph (c)(1) at quarterly

intervals, for 3 years from the date of issuance of the product

license, and then at annual intervals. The majority of the periodic

reports will be submitted annually since a large percentage of the

current licensed biological products have been licensed longer than 3

years. Section 600.80(i) requires the licensed manufacturers to

maintain for a period of 10 years records of all adverse experiences

known to the licensed manufacturer, including raw data and any

correspondence relating to the adverse experiences. Section 600.81 (21

CFR 600.81) requires the licensed manufacturer to submit information

about the quantity of the product distributed under the product

license, including the quantity distributed to distributors at an

interval of every 6 months. The semiannual distribution report informs

FDA of the quantity, the lot number, and the dosage of different

products. Section 600.90 (21 CFR 600.90) requires a licensed

manufacturer to submit a waiver request with supporting documentation

when asking for waiving the requirement that applies to them under

Secs. 600.80 and 600.81.

Respondents to this collection of information are manufacturers of

biological products. In fiscal year (FY) 1996, there were approximately

72 licensed manufacturers, 3 of which submitted waiver requests under

Sec. 600.90 and were exempt from these AER requirements. This number

excludes those manufacturers who produce blood and blood components and

in vitro diagnostic licensed products because they are specifically

exempt from the regulations. In FY 1996, there were 1,616 15-day alert

reports, 5,903 periodic reports and 464 distribution reports submitted

to FDA. The number of 15-day alert report for postmarketing studies as

stated in Sec. 600.80(e) was minimal and is included in the total

number of 15-day alert reports. The burden hours required to complete

the MedWatch Form for Sec. 600.80(c)(1), (e), and (f) are reported

under OMB Control No. 0910-0291. FDA estimates the burden of this

collection of information as follows:

Table 1.--Estimated Annual Reporting Burden1

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Number of

21 CFR Section No. of Responses per Total Annual Hours per Total Hours

Respondents Respondent Responses Response

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600.80(c)(1) and 600.80(e) 69 23.4 1,616 1 1,616

600.80(c)(2) 69 85.6 5,903 1 5,903

600.81 69 6.7 464 1 464

600.90 3 1 3 1 3

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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

There are approximately 391 licensed manufacturers of biological

products. However, the number of recordkeepers listed for

Sec. 600.12(a) through (e) excluding (b)(2) is estimated to be 102.

This number excludes manufacturers of blood and blood components

because their burden hours for recordkeeping have been reported under

21 CFR 606.160 in OMB Control No. 0910-0116. The recordkeeping burden

is based on the number of lots released (9,027), the number of recalls

made (710) and the total number of AER reports received (7,519) for FY

1996. FDA estimates that the average time associated with recordkeeping

per lot is 32 hours, for recalls is 24 hours, and for adverse

experience reports is 1 hour. FDA estimates the burden of this

recordkeeping as follows:

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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600.12 102 88.5 9,027 2,832 288,864

600.12(b)(2) 391 1.8 710 43 16,813

600.80(i) 69 109 7,519 109 7,519

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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

[[Page 37396]]

Dated: June 29, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-18402 Filed 7-9-98; 8:45 am]

BILLING CODE 4160-01-F