[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