[Federal Register Volume 73, Number 32 (Friday, February 15, 2008)]
[Notices]
[Pages 8881-8883]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-2890]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0073] (formerly Docket No. 2002N-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 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 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 April 15, 2008.

ADDRESSES: Submit electronic comments on the collection of information 
to http://www.regulations.gov. 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: JonnaLynn P. Capezzuto, Office of the 
Chief Information Officer (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, 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

[[Page 8882]]

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 AER 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 licensed 
manufacturers 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. These are known as 
postmarketing 15-day Alert reports. Section 600.80(c)(1) also requires 
licensed manufacturers to submit any followup 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 for an adverse experience 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 
licensed manufacturers to report each adverse experience not reported 
in a postmarketing 15-day Alert report at quarterly intervals, for 3 
years from the date of issuance of the biologics license, and then at 
annual intervals. The majority of these periodic reports will be 
submitted annually because a large percentage of currently licensed 
biological products have been licensed longer than 3 years. Section 
600.80(i) requires 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 requires licensed manufacturers to 
submit, at an interval of every 6 months, information about the 
quantity of the product distributed under the biologics license, 
including the quantity distributed to distributors. These semiannual 
distribution reports provide FDA with important information about 
products distributed under biologics licenses, including the quantity, 
certain lot numbers, labeled date of expiration, number of dosage 
units, and date of release. Under Sec.  600.90, a licensed manufacturer 
may submit a waiver request for any requirements that applies to the 
licensed manufacturer under Sec.  600.80 and 600.81. A waiver request 
submitted under Sec.  600.90 must include supporting documentation.
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of a product 
including any recalls. These recordkeeping requirements serve 
preventative and remedial purposes by establishing accountability and 
traceability in the manufacture and distribution of products. These 
requirements also enable FDA to perform meaningful inspections.
    Section 600.12 requires, among other things, concurrently with the 
performance of each step 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, manufacturers 
must maintain records of sterilization of equipment and supplies, 
animal necropsy records, and records in cases of divided manufacturing 
of a product. Section 600.12(b)(2) requires manufacturers to maintain 
complete records 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 the Center for Biologics 
Evaluation and Research and Center for Drug Evaluation and Research, 
FDA, in fiscal year (FY) 2006. Based on information obtained from FDA's 
database system, there were 88 licensed biologics manufacturers. This 
number excludes those manufacturers who produce blood and blood 
components and in-vitro diagnostic licensed products, because Sec.  
600.80(k) specifically exempts manufacturers of these products from 
adverse experience reporting requirements. The total annual responses 
are based on the estimated number of submissions received annually by 
FDA in FY 2006. However, not all manufacturers have submissions in a 
given year and some may have multiple submissions. There were an 
estimated 23,835 15-day Alert reports, 21,872 periodic reports, and 179 
lot distribution reports submitted to FDA. The number of 15-day Alert 
reports for postmarketing studies under Sec.  600.80(e) is included in 
the total number of 15-day Alert reports. FDA received 6 requests for 
waiver under Sec.  600.90, all of which were granted. The hours per 
response are based on FDA experience. 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 Burden\1\
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                         No. of        Annual Frequency     Total Annual        Hours per
  21 CFR Section      Respondents        per Response        Responses           Response         Total Hours
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600.80(c)(1) and                  88             270.85             23,835                  1             23,835
 600.80(e)
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600.80(c)(2)                      88             248.55             21,872                 28            612,416
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600.81                            88               2.03                179                  1                179
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600.90                             6                  1                  6                  1                  6
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[[Page 8883]]

 
Total                                                                                                    636,436
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\1\ There are no capital 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 FDA's database system, there were 303 
licensed manufacturers of biological products in FY 2006. However, the 
number of recordkeepers listed for Sec.  600.12(a) through (e) 
excluding (b)(2) is estimated to be 112. 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 total annual records is based on the annual 
average of lots released (5,291), number of recalls made (1,841), and 
total number of adverse experience reports received (45,707) in FY 
2006. The hours per record are based on FDA experience.
    FDA estimates the burden of this recordkeeping as follows:

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
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                                       Annual Frequency
  21 CFR Section         No. of              per            Total Annual        Hours per         Total Hours
                     Recordkeepers      Recordkeeping         Records          Recordkeeper
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600.12                           112              47.24              5,291                 32            169,312
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600.12(b)(2)                     303               6.08              1,841                 24             44,184
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600.80(i)                         88             519.40             45,707                  1             45,707
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Total                                                                                                    259,203
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: February 8, 2008.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E8-2890 Filed 2-14-08; 8:45 am]
BILLING CODE 4160-01-S