[Federal Register Volume 67, Number 110 (Friday, June 7, 2002)]
[Notices]
[Pages 39406-39409]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-14390]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 01N-0587]
Agency Information Collection Activities; Submission for OMB
Review; 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 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
July 8, 2002.
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.
General Licensing Provisions: Biologics License Application, Changes to
an Approved Application, Labeling Forms FDA 356h and 2567; and
Revocation and Suspension (OMB Control Number 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
[[Page 39407]]
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 postmarketing 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. 606.110(b), 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 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 paragraph 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 Sec.
610.53(d) (21 CFR 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 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 number 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 Form 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 and 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 Form 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 number 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 of this document to account for the rare
[[Page 39408]]
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.
One letter of comment was received in response to the 60-day notice
on the information collection in which we received one comment on the
proposed information collection.
The comment stated that we should revise various regulations to
harmonize regulations between CBER and CDER. The comment cited many
specific provisions, with none of the cited provisions being affected
by the proposed information collection, and recommended specific
changes to those provisions. For example, the comment asked that we
delete Sec. 610.12 (21 CFR 610.12) regarding sterility for bulk
materials, that we revise 21 CFR 610.11, Sec. 610.12, and 21 CFR 610.13
and 610.30 to delete references to specific tests, and that we redefine
``manufacturer'' in 21 CFR 600.3(t). The comment also asked us to
address ``outdated'' safety reporting regulations; to permit multiple
product facilities (citing 21 CFR 600.11(e)(3)); and to expedite
followup actions after inspections.
The comment's suggested regulatory revisions pertain to provisions
or matters that are outside the scope of the proposed information
collection. Consequently, we decline to adopt the comment's
recommendations.
The comment relevant to the information collection in the 60-day
notice stated that Form FDA 2567 is only used to submit labels to CBER
and that CDER does not use this form. The comment stated that the
requirement to use only one form for one Center imposes an additional
burden (but did not describe the additional burden), and suggested that
CBER and CDER use the same form or not use the form at all.
We are considering whether to retain Form FDA 2567 for labeling
purposes, but because the issue of eliminating the form is complex, we
won't have a decision on the matter before the OMB approval expires.
Therefore, we are renewing the form until a final decision is reached
on the use of the form. Manufacturers already have the option of
submitting to CBER and CDER Form FDA 2253 for the submission of
advertising and promotional labeling. However, any additional burden of
submitting the form with a biologics license application is minimal
because the time required to complete this form is estimated to average
10 minutes.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Form
21 CFR FDA No. of Respondents Annual Frequency per Total Annual Hours per Total Hours
Part\2\ No. Response Responses Response
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601.2(a), 2567 22 3.64 80 1,600 128,000
610.60, and
610.61, 356h
and
610.62
601.12(b)( 356h 168 4.98 837 80 66,960
1) and
(b)(3)
601.12(c)( 356h 119 6.63 789 50 39,450
1) and
(c)(3)
601.12(c)( 356h 58 3.52 204 50 10,200
5)
601.12(d) 356h 83 1.72 143 10 1,430
601.12(e) 356h 70 1 70 20 1,400
601.12(f)( 2567 37 2.08 77 40 3,080
1)
601.12(f)( 2567 45 1 45 20 900
2)
601.12(f)( 2567 20 1 20 10 200
3)
601.12(f)( 2567 42 36.88 1,549 10 15,490
4) and
601.45
600.15(b) 356h 1 1 1 8 8
610.53(d) 356h 1 1 1 8 8
601.25(b)( NA 0 0 0 0 0
3)
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 356h 350 4.59 1,606 20 32,120
and
Resubmiss
ions
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).
[[Page 39409]]
Dated: May 31, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-14390 Filed 6-6-02; 8:45 am]
BILLING CODE 4160-01-S