[Federal Register Volume 68, Number 15 (Thursday, January 23, 2003)]
[Notices]
[Pages 3262-3264]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-1406]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02N-0418]


Agency Information Collection Activities; Submission for OMB 
Review; 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 that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by 
February 24, 2003.

[[Page 3263]]


ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Stuart Shapiro, Desk Officer for FDA.

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: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Adverse Experience Reporting for Licensed Biological Products (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 (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 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 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 years 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 reports 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.
    In the Federal Register of October 4, 2002 (67 FR 62249), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.

[[Page 3264]]



                                 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)                    95             146.72               13,938                  1             13,938
 and (e)
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600.80(c)(2)                    95             106.34               10,102                 28            282,856
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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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Total                                                                                                    297,145
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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 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 years 
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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                       No. of         Annual Frequency      Total Annual        Hours per
21 CFR  Section     Respondents         per Response         Responses           Response         Total  Hours
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600.12                         111              60.78                6,747                 32            215,904
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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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Total                                                                                                    279,448
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: January 14, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-1406 Filed 1-22-03; 8:45 am]
BILLING CODE 4160-01-S