[Federal Register Volume 67, Number 27 (Friday, February 8, 2002)]
[Notices]
[Pages 6036-6039]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-3080]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01N-0587]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; General Licensing Provisions: Biologics License 
Application, Changes to an Approved Application, Labeling Forms FDA 
356h and 2567; 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 
requirements relating to the general licensing provisions regarding 
biologics license applications, changes to an approved application, 
labeling, and revocation and suspension, and the use of Forms FDA 356h 
and 2567.

[[Page 6037]]


DATES: Submit written or electronic comments on the collection of 
information by April 9, 2002.

ADDRESSES: Submit electronic comments on the collection of information 
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.

General Licensing Provisions: Biologics License Application, 
Changes to an Approved Application, Labeling Forms FDA 356h and 
2567; and Revocation and Suspension (OMB Control No. 0910-0338)--
Extension

    Under section 351 of the Public Health Service Act (the PHS Act) 
(42 U.S.C. 262), manufacturers of biological products must submit a 
license application for FDA review and approval before 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 ensure 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). Section 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. The container and 
package labeling requirements are provided under 21 CFR 610.60, 610.61, 
and 610.62. Section 601.12(a) provides the general requirements for 
submitting a change to an approved application. 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. The appropriate procedure depends 
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 applicants to submit a protocol, or 
change to a protocol, as a supplement requiring FDA approval before 
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 applicants to report to 
FDA advertising and promotional labeling and any changes. 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. 
Section 601.27(a) requires that applications for new biological 
products contain data that are adequate to assess the safety and 
effectiveness of the biological product for the claimed indications in 
pediatric subpopulations, and to support dosing and administration 
information. Section 601.27(b) provides that an applicant may request a 
deferred submission of some or all assessments of safety and 
effectiveness required under Sec. 601.27(a). Section 601.27(c) provides 
that an applicant may request a full or partial waiver of the 
requirements under Sec. 601.27(a). Section 601.28 requires sponsors of 
licensed biological products to submit the information in section 
601.28(a), (b), and (c) to the Center for Biologics Evaluation and 
Research (CBER) each year, within 60 days of the anniversary date of 
approval of the license. Section 601.28(a) requires sponsors to submit 
to FDA a brief summary stating whether labeling supplements for 
pediatric use have been submitted and whether new studies in the 
pediatric population to support appropriate labeling for the pediatric 
population have been initiated. Section 601.28(b) requires sponsors to 
submit to FDA an analysis of available safety and efficacy data in the 
pediatric population and changes proposed in the labeling based on this 
information. Section 601.28(c) requires sponsors to submit to FDA a 
statement on the current status of any post-marketing studies in the 
pediatric population performed by, on or behalf of, the applicant. 
Sections 601.33 through 601.35 clarify the information to be submitted 
in an application to FDA to evaluate the safety and effectiveness of in 
vivo radiopharmaceuticals. In addition to Secs. 601.2 and 601.12, there 
are other regulations in parts 640, 660, and 680 (21 CFR parts 640, 
660, and 680) that relate to information to be submitted in a license 
application or supplement for certain blood or allergenic products: 
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), 660.51(a)(4), and 680.1(b)(2)(iii). In 
the table 1 of this document, the burden associated with the 
information collection requirements in these regulations is included in 
the burden estimate for Secs. 601.2 and 601.12. A regulation may be 
listed under more than one section of Sec. 601.12 due to the type of 
category under which a change to an approved application may be 
submitted. In addition, the burden associated with the information 
collection requirements in Sec. 601.27(a) and Secs. 601.33 through 
601.35 is included in the burden estimate for Sec. 601.2 since these 
regulations deal with information to be provided in an application. 
Sections 600.15(b) (21 CFR 600.15(b))and 610.53(d) require the 
submission of a request for an exemption or modification regarding the 
temperature requirements during

[[Page 6038]]

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 submit to FDA 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. Section 680.1(c) 
requires manufacturers to update annually the list of source materials 
and the suppliers of the materials.
    In July 1997, FDA revised Form FDA 356h ``Application to Market a 
New Drug, Biologic, or an Antibiotic Drug for Human Use'' to harmonize 
application procedures between CBER and the Center for Drug Evaluation 
and Research (CDER). The application form serves primarily as a 
checklist for firms to gather and submit to the agency studies and data 
that have been completed. The checklist helps to ensure that the 
application is complete and contains all the necessary information, so 
that delays due to lack of information may be eliminated. The form 
provides key information to the agency for efficient handling and 
distribution to the appropriate staff for review. The estimated burden 
hours for submissions using FDA Form 356h to CDER are reported under 
OMB Control No. 0910-0001.
    Form FDA 2567 ``Transmittal of Labels'' and Circulars( 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 CBER. For 
advertisements and promotional labeling, manufacturers of licensed 
biological products may submit to CBER either Form FDA 2567 or FDA 
2253. Form FDA 2253 was previously used only by drug manufacturers 
regulated by CDER. In August of 1998, FDA revised and harmonized Form 
FDA 2253 so the form may 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.
    Under table 1 of this document, the number of respondents is based 
on the estimated annual number of manufacturers that submitted the 
required information to FDA in fiscal year (FY) 2000, or the number of 
submissions received in FY 2000. Based on information obtained from 
CBER's database system, 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 are based on the estimated number of submissions 
(e.g., license applications, labeling and other supplements, protocols, 
advertising and promotional labeling, notifications) received annually 
by FDA. Based on previous estimates, the rate of submissions is not 
expected to change significantly in the next few years. The hours per 
response are based on information provided by industry and past FDA 
experience with the various submissions or notifications. The hours per 
response include the time estimated to prepare the various submissions 
or notifications to FDA, and, as applicable, the time required to fill 
out the appropriate form and collate the documentation. Additional 
information regarding these estimates is provided below as necessary.
    Under Secs. 601.12(f)(4) and 601.45, manufacturers of biological 
products may use either Form FDA 2567 or FDA 2253 to submit advertising 
and promotional labeling. In FY 2000, CBER received 4,302 submissions 
of advertising and promotional labeling from 117 manufacturers. FDA 
estimates that approximately 36 percent of those submissions were 
received with Form FDA 2567 resulting in an estimated 1,549 submissions 
by 42 manufacturers. The burden hours for the remaining submissions 
received using Form FDA 2253 are reported under OMB Control No. 0910-
0376.
    Under Secs. 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 to account for the 
rare instance in which a request may be made.
    Under Sec. 601.25(b)(3), FDA estimates no burden for this 
regulation since all requested data and information had been submitted 
by 1974. Under Sec. 601.26(f), FDA estimates no burden for this 
regulation since 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 
deem it necessary for further study. As a result, any changes to 
product labeling would be reported under Sec. 601.12.
    Under Sec. 601.6(a), the total annual responses is based on FDA 
estimates that establishments may 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 a biologics license.
    There were also 1,585 amendments to an unapproved application or 
supplement and 21 resubmissions (total of 1,606 submissions) submitted 
in FY 2000 using Form FDA 356h.
    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\2\                     Form FDA No.           Respondents     per Response       Responses       Response        Total Hours
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601.2(a), 610.60, 610.61, and 610.62     2567/356h                         22                3.64            80           1,600          128,000
601.12(b)(1) and (b)(3)                  356h                             168                4.98           837              80           66,960

[[Page 6039]]

 
601.12(c)(1) and (c)(3)                  356h                             119                6.63           789              50           39,450
601.12(c)(5)                             356h                              58                3.52           204              50           10,200
601.12(d)                                356h                              83                1.72           143              10            1,430
601.12(e)                                356h                              70                1               70              20            1,400
601.12(f)(1)                             2567                              37                2.08            77              40            3,080
601.12(f)(2)                             2567                              45                1               45              20              900
601.12(f)(3)                             2567                              20                1               20              10              200
601.12(f)(4) and 601.45                  2567                              42               36.88         1,549              10           15,490
600.15(b)                                356h                               1                1                1               8                8
610.53(d)                                356h                               1                1                1               8                8
601.25(b)(3)                             NA                                 0                0                0               0                0
601.26(f)                                NA                                 0                0                0               0                0
601.27(b)                                NA                                 5                1                5              24              120
601.27(c)                                NA                                 3                1.33             4               8               32
601.28(a)                                NA                                69                1               69               8              552
601.28(b)                                NA                                69                1               69              24            1,656
601.28(c)                                NA                                69                1               69               1.5            103.5
601.5(a)                                 NA                                25                1               25                .33             8.25
601.6(a)                                 NA                                 2               21               42                .33            14
680.1(c)                                 NA                                10                1               10               2               20
Amendments/Resubmissions                 356h                             350                4.59         1,606              20           32,120
      Total                                                                                                                              301,751.75
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The reporting requirement under Secs.  601.27(a), 601.33, 601.34, 601.35, and 680.1(b)(2)(iii) is included in the estimate under Sec.  601.2(a). The
  reporting requirement under Secs.  640.6, 640.17, 640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), and 640.72(a) and (b)(2) is included in the
  estimate under Sec.  601.12(b). The reporting requirement under Secs.  640.25(c) and 640.56(c) is also included in the estimate under Sec.
  601.12(c)(3).


    Dated: February 1, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-3080 Filed 2-7-02; 8:45 am]
BILLING CODE 4160-01-S