[Federal Register: September 25, 2000 (Volume 65, Number 186)]
[Notices]               
[Page 57612-57614]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25se00-66]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1502]

 
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 November 24, 2000.

ADDRESSES: Submit electronic comments on the collection of information 
via the Internet at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.accessdata.fda.gov/scripts/oc/dockets/comments/commentdocket.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 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 600.12 and Part 600 Subpart D (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 adverse experience reporting requirements 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 adverse 
experience reporting 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.
    Section 600.80(c)(1) (21 CFR 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 (21 CFR 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 (21 CFR

[[Page 57613]]

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 Secs. 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 (21 CFR 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 information collection are manufacturers of 
biological products. In fiscal year (FY) 99 there were approximately 79 
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. FDA received four waiver 
requests under Sec. 600.90, of which one was approved for exemption of 
the AER requirements. In FY 99, there were an estimated 3,662 15-day 
alert reports, 13,238 periodic reports, and 502 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. 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 information collection 
as follows:

                                  Table 1.--Estimated Annual Reporting Burden1
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                                                      Annual
         21 CFR section              Number of     frequency per   Total annual      Hours per      Total hours
                                    respondents      response        responses       response
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600.80(c)(1) and (e)                   78              46.95        3,662               1           3,662
600.80(c)(2)                           78             169.72       13,238               1          13,238
600.81                                 78               6.44          502               1             502
600.90                                  4               1               4               1               4
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Total                                                                                             17,407
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\1\There are no captital costs or operating and maintenance costs associated with this collection of
  information.

    There are approximately 343 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 No. 0910-0116. The 
recordkeeping burden is based on the number of lots released (6,446), 
the number of recalls made (1,176) and the total number of AER reports 
received (16,900) for FY 99. The hours per record are based on FDA 
experience.
    FDA estimates the burden of this recordkeeping as follows:

                                Table 2.--Estimated Annual Recordkeeping Burden1
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                                                      Annual
         21 CFR section              Number of     frequency of    Total annual      Hours per      Total hours
                                   recordkeepers   recordkeeping      records         record
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600.12                                111              58.1         6,446              32         206,272
600.12(b)(2)                          343               3.4         1,176              24          28,224
600.80(i)                              79             213.92       16,900               1          16,900
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Total                                                                                             251,396
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.



[[Page 57614]]

    Dated: September 19, 2000.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 00-24477 Filed 9-22-00; 8:45 am]
BILLING CODE 4160-01-F