[Federal Register: November 3, 2004 (Volume 69, Number 212)]
[Notices]               
[Page 64069-64071]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03no04-80]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004N-0469]

 
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 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 the information collection 
requirements relating to FDA's adverse experience

[[Page 64070]]

reporting (AER) for licensed biological products, and general records 
associated with the manufacture and distribution of biological 
products.

DATES: Submit written or electronic comments on the collection of 
information by January 3, 2004.

ADDRESSES: Submit electronic comments on the collection of information 
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written comments on the 

collection of information to the Division of Dockets Management (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: Jonna 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 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 these topics: (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 
which 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 biological 
product'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, whether foreign or domestic, as soon as possible but in no 
case later than 15 calendar days of initial receipt of the information 
by the licensed manufacturer and to submit any follow-up reports within 
15 calendar days of receipt of new information or as requested by FDA. 
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)(i) 
at quarterly intervals, for 3 years from the date of issuance of the 
biologics 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 biologics license, 
including the quantity distributed to distributors at an interval of 
every 6 months. The semiannual distribution report informs FDA of the 
quantity, certain lot numbers, labeled date of expiration, the number 
of doses, and date of release. Under Sec.  600.90, a licensed 
manufacturer may submit a waiver request that applies to the licensed 
manufacturer under Sec. Sec.  600.80 and 600.81. A waiver request 
submitted under Sec.  600.90 must be submitted with supporting 
documentation.
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of products 
including the 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. In 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 fiscal year (FY) 2002 and 
2003. Based on information obtained from the Center for Biologics 
Evaluation and Research's

[[Page 64071]]

(CBER's) database system, there were 90 licensed biologics 
manufacturers. This number excludes those manufacturers who produce 
blood and blood components and in-vitro diagnostic licensed products 
because these products are specifically exempt from the regulations 
under Sec.  600.80(k). The total annual responses are based on the 
average estimated number of submissions received annually by FDA for FY 
2002 and 2003. However, not all manufacturers have submissions in a 
given year and some may have multiple submissions. There were an 
estimated 15,126 15-day alert reports, 6,550 periodic reports, and 323 
lot distribution reports submitted to FDA. The number of 15-day alert 
report for postmarketing studies under Sec.  600.80(e) is included in 
the total number of 15-day alert reports. FDA received an average of 5 
waiver requests for FY 2002 and 2003 under Sec.  600.90, all of which 
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 collection of information as 
follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                                                        Annual Frequency       Total Annual
                 21 CFR Section                   No. of Respondents      per Response          Responses        Hours per Response      Total Hours
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600.80(c)(1) and 600.80(e)                                   90                  168.07            15,126                    1               15,126
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600.80(c)(2)                                                 90                   72.78             6,550                   28              183,400
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600.81                                                       90                    3.59               323                    1                  355
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600.90                                                        5                    1                    5                    1                    5
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Total                                                                                                                                       198,886
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\1\ There are no capitol costs or operating and maintenance costs associated with this collection of information.

    In 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 320 
licensed manufacturers of biological products in FY 2002 and 2003. 
However, the number of recordkeepers listed for Sec.  600.12(a) through 
(e) excluding paragraph (b)(2) is estimated to be 116. 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 (6,630), number of recalls made 
(1,958), and total number of AER reports received (35,484) in FY 2002 
and 2003. 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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                                                        No. of          Annual Frequency       Total Annual
                 21 CFR Section                     Recordkeepers      per Recordkeeping         Records         Hours per Response      Total Hours
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600.12                                                      116                   57.16             6,630                   32              212,160
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600.12(b)(2)                                                320                    6.12             1,958                   24               46,992
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600.80(i)                                                    90                  394.27            35,484                    1               35,484
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Total                                                                                                                                       294,636
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\1\ There are no capitol costs or operating and maintenance costs associated with this collection of information.


    Dated: October 27, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-24445 Filed 11-2-04; 8:45 am]

BILLING CODE 4160-01-S