[Federal Register Volume 67, Number 193 (Friday, October 4, 2002)]
[Notices]
[Pages 62249-62251]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-25193]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02N-0418]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Adverse Experience Reporting for Licensed Biological 
Products; and General Records

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 Registerconcerning 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 the information collection 
requirements relating to FDA?s adverse experience reporting (AER) for 
licensed biologicalproducts, and general records associated with the 
manufacture and distribution of biological products.

DATES: Submit written or electronic comments on the collection of 
information by December 3, 2002.

ADDRESSES: Submit electronic comments on the collection of information 
to http://www.accessdata.fda.gov/scripts/oc/dockets/edockethome.cfm. 
Submit written comments on the collection of information to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852. All documents 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 request

[[Page 62250]]

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, including each proposed extension 
of an existing collection of information, before submitting the 
collection to OMB for approval. To comply with this requirement, FDA is 
publishing notice of the proposed collection of information set forth 
in this document.
    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; and 
General Records--21 CFR Part 600 (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 AER requirements in part 600 (21 CFR part 600) 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 AER 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 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.
    The regulation in Sec.  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 manufacturer 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 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 requires a 
licensed manufacturer to submit a waiver request with supporting 
documentation when asking for waiving the requirement that applies to 
them under Sec. Sec.  600.80 and 600.81.
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of products 
including 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 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.
    Respondents to this collection of information are manufacturers of 
biological products. Under table 1 of this document, the number of 
respondents is based on the estimated number of manufacturers that 
submitted the required information to FDA in the year 2000 and 2001. 
Based on information obtained from the Center for Biologics Evaluation 
and Research's (CBER's) database system, there were approximately 95 
licensed manufacturers. 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. 
However, not all manufacturers may have any submissions in a given year 
and some may have multiple submissions. The total annual responses are 
based on the estimated number of submissions received annually by FDA. 
There were an estimated 13,938 15-day alert reports, 10,102 periodic 
reports, and 339 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. FDA received an average of 12 waiver requests under 
Sec.  600.90, of which 11 were approved for exemption of the AER 
requirements. The hours per response are based on FDA's experience. The 
burden hours required to complete the MedWatch Form for Sec.  
600.80(c)(1), (e), and (f) are reported under OMB control number 0910-
0291.
    FDA estimates the burden of this information collection as follows:

[[Page 62251]]



                                 Table 1.--Estimated Annual Reporting Burden\1\
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                                                                     Annual
                                                         No. of    Frequency    Total Annual      Hours    Total
                   21 CFR Section                     Respondents     per     [chyph]Responses     per     Hours
                                                                    Response                    Response
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600.80(c)(1) and (e)                                        95      146.72        13,938             1    13,938
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600.80(c)(2)                                                95      106.34        10,102            28    282,85
                                                                                                              6
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600.81                                                      95        3.57           339             1      339
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600.90                                                      12           1            12             1       12
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Totals                                                                                                     297,
                                                                                                            145
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\1\ There are no capitol costs or operating and maintenance costs associated with this collection of
  information.

    Under table 2 of this document, the number of respondents is based 
on the number of manufacturers subject to those regulations. Based on 
information obtained from CBER?s database system, there were 
approximately 329 licensed manufacturers of biological products. 
However, the number of recordkeepers listed for Sec.  600.12(a) through 
(e) excluding paragraph (b)(2) is estimated to be 111. This number 
excludes manufacturers of blood and blood components because their 
burden hours for recordkeeping have been reported under Sec.  606.160 
in OMB control number 0910-0116. The total annual records is based on 
the annual average of lots released (6,747), number of recalls made 
(1,646) and total number of AER reports received (24,040) in the year 
2000 and 2001. The hours per record are based on FDA's experience.
    FDA estimates the burden of this recordkeeping as follows:

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
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                                                                     Annual                        Hours
                 21 CFR Section                       No. of      Frequency of    Total Annual      per    Total
                                                  Recordkeepers  Recordkeeping  [chyph]Responses  Record   Hours
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600.12                                                  111          60.78           6,747           32   215,90
                                                                                                              4
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600.12(b)(2)                                            329           5.00           1,646           24   39,504
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600.80(i)                                                95         253.05          24,040            1   24,040
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Totals                                                                                                    279,44
                                                                                                              8
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: September 27, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-25193 Filed 10-3-02; 8:45 am]
BILLING CODE 4160-01-S