[Federal Register Volume 65, Number 45 (Tuesday, March 7, 2000)]
[Notices]
[Pages 12011-12013]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-5416]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-0726]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; General Licensing Provisions: Changes to an Approved 
Application, Labeling, and Revocation and Suspension

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 
requirement relating to the general licensing provisions regarding 
changes to an approved application, labeling, and revocation and 
suspension.

DATES: Submit written comments on the collection of information by May 
8, 2000.

ADDRESSES: 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 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 
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 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: (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.

General Licensing Provisions: Changes to an Approved Application, 
Labeling, and Revocation and Suspension (OMB Control Number 0910-
0315)--Extension

    Under Section 351 of the Public Health Services Act (PHS Act) (42 
U.S.C. 262), manufacturers of biological products must submit a license 
application for FDA review and approval prior to marketing a biological 
product in interstate commerce. Licenses may be issued only upon 
showing that the establishment and the products for which a license is 
desired meets standards prescribed in regulations designed to insure 
the continued safety, purity, and potency of such products. All such 
licenses are issued, suspended, and revoked as prescribed by 
regulations.
    In part 601 (21 CFR part 601), Sec. 601.2(a) requires a 
manufacturer of a biological product to submit an application with 
accompanying information, including labeling information, to FDA for 
approval to market a product in interstate commerce. Section 601.12(b), 
(c), and (d) requires applicants to follow specific procedures in 
informing FDA of each change, established in an approved license 
application, in the product, production process, quality controls, 
equipment, facilities, or responsible personnel depending on the 
potential for the change to have a substantial, moderate, minimal or no 
adverse effect on the safety or effectiveness of the product. Section 
601.12(e) requires

[[Page 12012]]

applicants to submit a protocol, or change to a protocol, as a 
supplement requiring FDA approval prior to distributing the product. 
Section 601.12(f)(1), (f)(2), and (f)(3) requires applicants to follow 
specific procedures in reporting labeling changes to FDA. Section 
601.12(f)(4) requires advertising and promotional labeling and any 
changes to be reported to FDA. Section 601.45 requires applicants to 
submit to the agency for consideration, during the preapproval review 
period, copies of all promotional materials, including promotional 
labeling as well as advertisements. In addition to Secs. 601.2 and 
601.12, there are other regulations that relate to certain information 
submitted in a license application or supplement as follows: Part 640 
(21 CFR part 640), specifically Secs. 640.6, 640.17, 640.21(c), 
640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a), and (b)(2); 21 
CFR 660.51(a)(4) and 680.1(b)(2)(iii) and (c). The burden associated 
with the information collection requirements in these regulations is 
included in the burden estimate for Sec. 601.2, reported under OMB 
Control No. 0910-0427, and Sec. 601.12 in table 1 of this document. 
Sections 600.15(b) and 610.53(d) require the submission of a request 
for an exemption or modification regarding the temperature requirements 
during shipment and from dating periods, respectively, for certain 
biological products. Section 601.25(b) requests interested persons to 
submit, for review and evaluation by an advisory review panel, 
published and unpublished data and information pertinent to a 
designated category of biological products that have been licensed 
prior to July 1, 1972. Section 601.26(f) requests that licensees submit 
to FDA a written statement intended to show that studies adequate and 
appropriate to resolve questions raised about a biological product have 
been undertaken for a product if designated as requiring further study 
under the reclassification procedures. Section 601.5(a) requires a 
licensee to give notice of its intention to discontinue manufacture of 
a product or all products. Section 601.6(a) requires the licensee to 
notify selling agents and distributors upon suspension of its license, 
and provide FDA with records of such notification.
    Form FDA 2567 is used by manufacturers of licensed biological 
products to submit labeling (e.g., circulars, package labels, container 
labels, etc.) and labeling changes for FDA review and approval. The 
labeling information is submitted with the form for license 
applications, supplements, or as part of an annual report. Form FDA 
2567 is also used for the transmission of advertisements and 
promotional labeling. Form FDA 2567 serves as an easy guide to assure 
that the manufacturer has provided the information required for 
expeditious handling of their labeling by the Center for Biologics 
Evaluation and Research (CBER). For advertisements and promotional 
labeling, manufacturers of licensed biological products may submit to 
CBER either Form FDA 2567 or 2253. Form FDA 2253 was previously used 
only by drug manufacturers regulated by the Center for Drugs Evaluation 
and Research. In August of 1998, FDA revised and harmonized Form FDA 
2253 to enable the form to be used to transmit specimens of promotional 
labeling and advertisements for biological products as well as for 
prescription drugs and antibiotics. The revised, harmonized form 
updates the information about the types of promotional materials and 
the codes that are used to clarify the type of advertisement or 
labeling submitted; clarifies the intended audience for the 
advertisements or promotional labeling (e.g., consumers, professionals, 
news services); and helps ensure that the submission is complete.
    The number of respondents is based on the estimated annual number 
of manufacturers that submitted the required information to FDA. There 
are an estimated 350 licensed biologics manufacturers. However, not all 
manufacturers will have any submissions in a given year and some may 
have multiple submissions. The total annual responses is based on the 
estimated number of submissions (i.e., license applications, labeling 
and other supplements, protocols, advertising and promotional labeling, 
notifications) received annually by FDA. The rate of submissions are 
not expected to change significantly in the next few years. The hours 
per response are based on past FDA experience with the various 
submissions or notifications. Additional information regarding these 
estimates is provided below as necessary.
    Under Sec. 601.2(a), the total annual responses is based on the 
numbers of applications submitted to FDA for approval to market a 
biological product. The estimated burden hours include the time 
required to fill out the form and collate the documentation. The 
estimated burden hours to prepare the labeling information submitted 
with a license application are included in the burden hours to submit a 
license application which are reported under OMB Control No. 0910-0427.
    Under Sec. 601.12(f)(1), (f)(2), and (f)(3), the estimated burden 
hours include the time to prepare the supplement, fill out the form, 
and collate the documentation.
    Under Secs. 601.12(f)(4) and 601.45, manufacturers of biological 
products may use either Form FDA 2567 or Form FDA 2253 to submit 
advertising and promotional labeling. In fiscal year 1999, CBER 
received 3,784 submissions of advertising and promotional labeling from 
114 manufacturers. FDA estimates that approximately 55 percent of those 
submissions were received with Form FDA 2567 resulting in an estimated 
2,081 submissions by 63 manufacturers. The estimated burden hours 
include the time to prepare the submission, fill out the form, and 
collate the documentation. The burden hours for the remaining 
submissions received using Form FDA 2253 are reported under OMB Control 
No. 0910-0376.
    Under Secs. 601.12(b) through (d), and 601.12(e), the estimated 
burden hours include the time to prepare the appropriate supplement or 
protocol, respectively, and collate the documentation.
    Under Secs. 600.15(b) (21 CFR 600.15(b)) and 610.53(d), FDA 
receives very few requests for an exemption or modification to the 
requirements, therefore, FDA has estimated one respondent per year in 
table 1 of this document to account for the rare instance in which a 
request may be made. The estimated burden hours include the time to 
prepare the request for modification or exemption.
    Under Sec. 601.25(b)(3), FDA estimates no burden for this 
regulation because all requested data and information had been 
submitted by 1974. Under Sec. 601.26(f), FDA estimates no burden for 
this regulation because there are no products designated to require 
further study and none are predicted in the future. However, based on 
the possible reclassification of a product, the labeling for the 
product may need to be revised, or a manufacturer, on its own 
initiative, may believe further study is necessary. As a result, any 
changes to product labeling would be reported under Sec. 601.12. The 
information collection requirements for Sec. 601.12 are reported under 
OMB control number 0910-0315.
    Under Sec. 601.5(a), the total annual responses are based on the 
estimated annual number of notifications received by FDA to discontinue 
either an establishment and/or product license(s). The estimated burden 
hours include the time to prepare and submit a letter of 
discontinuance.

[[Page 12013]]

    Under Sec. 601.6(a), the number of respondents (21) is based on FDA 
estimates that establishments would need to notify an average of 20 
selling agents and distributors of such suspension and provide FDA with 
the records of such notification. The number of respondents is based on 
the estimated annual number of suspensions by FDA of an establishment 
or product license(s). The estimated burden hours includes the time to 
prepare a notification letter and submit record of such notification to 
FDA.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden \1\
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                                                      Annual
 21 CFR Section    Form FDA No.       No. of       frequency per   Total annual      Hours per      Total Hours
                                    respondents      response        responses       response
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601.2(a)         2567 and 356h         17               3.71           63               2             126
                  \2\
601.12(f)(1)     2567                  12               1              12              40             480
601.12(f)(2)     2567                  10               1              10              20             200
601.12(f)(3)     2567                  70               1.43          100              10           1,000
601.12(f)(4)     2567                  63              33.03        2,081              10          20,810
 and 601.45
601.12(b)(1)     356 h\2\             190               4.75          903              80          72,240
 and (b)(3)
601.12(c)(1)     356h \2\              98               2.60          255              50          12,750
 and (c)(3)
601.12(c)(5)     356h \2\              34               1.21           41              50           2,050
601.12(d)        356h \2\             166               1.37          227              10           2,270
601.12(e)        356h \2\              14               1.43           20              20             400
600.15(b)        356h \2\               1               1               1               8               8
610.53(d)        356h \2\               1               1               1               8               8
601.25(b)(3)     NA                     0               0               0               0               0
601.26(f)        NA                     0               0               0               0               0
601.5(a)         NA                    33               1              33                .33           11
601.6(a)         NA                     2              10.50           21                .33            7
Total                                                                                             112,360
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ The burden hours for the use of Form FDA 356h are reported under OMB Control No. 0910-0427.


    Dated: February 29, 2000.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 00-5416 Filed 3-6-00; 8:45 am]
BILLING CODE 4160-01-F