Supporting Statement for

General Licensing Provisions: Biologics License Application, Changes to
an Approved Application, Labeling, Revocation and Suspension,
Postmarketing Studies Status Reports, and Forms FDA 356h and 2567

Existing OMB \# 0910-0338

# JUSTIFICATION

## Need and Legal Basis

The Food and Drug Administration (FDA) is requesting an extension of
Office of Management and Budget (OMB) Control No. 0910-0338 and OMB
approval of the information collection provisions including Forms FDA
356h and 2567 (Tab A). The information collection provisions are listed
below (Tab B):

  ---------------------- ------------------------- ---------------------------------------
  21 CFR Section         Category                  Description

  600.15(b), 610.53(d)   Reporting                 Require the submission of a request for
                                                   an exemption or modification regarding
                                                   the temperature requirements during
                                                   shipment and regarding dating periods,
                                                   respectively, for certain biological
                                                   products.

  601.2(a), 610.60,      Reporting                 Require manufacturers of a biological
  610.61, 610.62                                   product to submit an application with
                                                   accompanying information, including
                                                   container and package labeling
                                                   information, to FDA for approval to
                                                   market a product in interstate
                                                   commerce.

  601.5(a)               Reporting                 Requires licensees to submit to FDA
                                                   notice of its intention to discontinue
                                                   manufacture of a product or all
                                                   products.

  601.6(a)               Reporting                 Requires licensees to notify selling
                                                   agents and distributors upon suspension
                                                   of its license, and provide FDA with
                                                   records of such notification.

  601.12(a)(2)           Reporting                 Requires, generally, that the holder of
                                                   an approved biologics license
                                                   application must assess the effects of
                                                   a manufacturing change before
                                                   distributing a biological product made
                                                   with the change.

  601.12(a)(4)           Reporting                 Requires, generally, that the
                                                   applicants must promptly review all
                                                   promotional labeling and advertising to
                                                   make it consistent with certain
                                                   labeling changes implemented.

  601.12(a)(5)           Reporting                 Requires applicants to include a list
                                                   of all changes contained in the
                                                   supplement or annual report; for
                                                   supplements, this list must be provided
                                                   in the cover letter.

  601.12(b)(1)/(b)(3),   Reporting                 Require applicants to follow specific
  601.12(c)(1)/(c)(3),                             procedures to inform FDA of each
  601.12(c)(5), and                                change, in the product, production
  601.12(d)(1)/(d)(3)                              process, quality controls, equipment,
                                                   facilities, responsible personnel or
                                                   labeling established in an approved
                                                   license application. The appropriate
                                                   procedure depends on the potential for
                                                   the change to have a substantial,
                                                   moderate, or minimal adverse effect on
                                                   the identity, strength, quality,
                                                   purity, or potency of the product as
                                                   they may relate to the safety or
                                                   effectiveness of the product.

  601.12(b)(4)           Reporting                 Applicants may request FDA to expedite
                                                   its review of a supplement for public
                                                   health reasons or if a delay in making
                                                   the change described in it would impose
                                                   an extraordinary hardship of the
                                                   applicant.

  601.12(e)              Reporting                 Requires applicants to submit a
                                                   protocol, or change to a protocol, as a
                                                   supplement requiring FDA approval
                                                   before distributing the product.

  601.12(f)(1),          Reporting                 Require applicants to follow specific
  601.12(f)(2),                                    procedures in reporting labeling
  601.12(f)(3)                                     changes to FDA.

  601.12(f)(4)           Reporting                 Requires applicants to report to FDA
                                                   advertising and promotional labeling
                                                   and any changes.

  601.14                 Reporting                 Requires the content of labeling
                                                   required in § 201.100(d)(3) must be in
                                                   electronic format and in a form that
                                                   FDA can process, review, and archive.

  601.25(b)(3)           Reporting                 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.

  601.26(f)              Reporting                 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.

  601.27(a)              Reporting                 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 sub-populations, and to
                                                   support dosing and administration
                                                   information.

  601.27(b)              Reporting                 Provides that an applicant may request
                                                   a deferred submission of some or all
                                                   assessments of safety and effectiveness
                                                   required under 601.27(a).

  601.27(c)              Reporting                 Provides that an applicant may request
                                                   a full or partial waiver of the
                                                   requirements under 601.27(a).

  601.28(a)              Reporting                 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.

  601.28(b)              Reporting                 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.

  601.28(c)              Reporting                 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.

  601.33, 601.34, 601.35 Reporting                 Clarify the information required to be
                                                   submitted in an application to FDA to
                                                   evaluate the safety and effectiveness
                                                   of in vivo radiopharmaceuticals.

  601.45                 Reporting                 Requires applicants of biological
                                                   products for serious or
                                                   life-threatening illnesses to submit to
                                                   the agency for consideration, during
                                                   the pre-approval review period, copies
                                                   of all promotional materials, including
                                                   promotional labeling as well as
                                                   advertisements.

  601.70(b) and (d)      Reporting                 Requires each applicant of a licensed
                                                   biological product to submit annually a
                                                   report, accompanied by Form FDA 2252 to
                                                   FDA on the status of postmarketing
                                                   studies for each approved application.
                                                   Two copies of each report must be
                                                   submitted.

  601.91(b)(3)           Reporting                 Requires applicants to prepare and
                                                   provide labeling with relevant
                                                   information to patient or potential
                                                   patient for biological products
                                                   approved under the subpart when human
                                                   efficacy studies are not ethical or
                                                   feasible (or based on efficacy studies
                                                   conducted in animals alone).

  601.93                 Reporting/Recordkeeping   Provides that biological products
                                                   approved under subpart H are subject to
                                                   the postmarketing recordkeeping and
                                                   safety reporting applicable to all
                                                   approved biological products.

  601.94                 Reporting                 Requires applicants to submit to the
                                                   agency for consideration during
                                                   preapproval review period copies of all
                                                   promotional materials including
                                                   promotional labeling as well as
                                                   advertisements.

  606.110(b)             Reporting                 Requires applicants to submit requests
                                                   for approval to perform plasmapheresis
                                                   of donors who do not meet certain donor
                                                   requirements for the collection of
                                                   plasma containing rare antibodies.

  610.11(g)(2)           Reporting                 Provides that manufacturers of certain
                                                   biological products may request an
                                                   exemption from the general safety test
                                                   requirements.

  610.67                 Reporting                 Requires certain biological products to
                                                   comply with the bar code requirements
                                                   at § 201.25.

  680.1(c)               Reporting                 Requires manufacturers to update
                                                   annually their license file with the
                                                   list of source materials and the
                                                   suppliers of the materials.

  Amendments/            Reporting                 Includes amendments to an unapproved
  Resubmissions                                    application or supplement or
                                                   resubmission of a license application.

  601.91(b)(2)(iii)      Recordkeeping             Requires, in certain circumstances,
                                                   postmarketing restrictions as needed to
                                                   ensure the safe use of the biological
                                                   products distribution conditioned on
                                                   specified recordkeeping requirements.
  ---------------------- ------------------------- ---------------------------------------

In addition to §§ 601.2 and 601.12, there are other regulations in 21
CFR 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*:* §§ 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), 680.1(b)(2)(iii), and 680.1(d). In the table 1 of section
12 of this document, the burden associated with the information
collection requirements in these regulations is included in the burden
estimate for §§ 601.2 and/or 601.12. A regulation may be listed under
more than one section of § 601.12 due to the type of category under
which a change to an approved application may be submitted.

There are also additional container and/or package labeling requirements
for certain licensed biological products: § 640.70(a) for Source Plasma;
§ 640.74(b)(3) and (b)(4) for Source Plasma Liquid; § 640.84(a) and (c)
for Albumin; § 640.94(a) for Plasma Protein Fraction; § 660.2(c) for
Antibody to Hepatitis B Surface Antigen; § 660.28(a) and (b) for Blood
Grouping Reagent; § 660.35(a), (c through g), and (i through m) for
Reagent Red Blood Cells; § 660.45 for Hepatitis B Surface Antigen; and §
660.55(a) and (b) for Anti-Human Globulin. The burden associated with
the additional labeling requirements for submission of a license
application for these certain biological products is minimal because the
majority of the burden is associated with the requirements under §§
610.60 through 610.62 or § 809.10. Therefore, the burden estimates for
these regulations are included in the estimate under §§ 610.60 through
610.62 in table 1 of this document. The burden estimates associated with
§ 809.10 are approved under OMB Control No. 0910-0485 (expires June 30,
2008).

Under section 351 of the Public Health Services Act (the PHS Act) (42
U.S.C. 262) (Tab C), 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 130(a) of the Food and Drug Administration Modernization Act
(Public Law 105-115) amended the Federal Food, Drug, and Cosmetic Act
(the act,) by adding a new provision, section 506B of the act (21 U.S.C.
356b) (Tab D), requiring reports of postmarketing studies (PMSs) for
approved human drugs and licensed biological product. Section 506B of
the act provides FDA with additional authority to monitor the progress
of PMSs that applicants have made a commitment to conduct and requires
FDA to make publicly available information that pertains to the status
of these studies.

Under section 506B(a) of the act, applicants that have committed to
conduct a PMS for an approved human drug or licensed biological product
must submit to FDA a status report of the progress of the study or the
reasons for the failure of the applicant to conduct the study. This
report must be submitted within 1 year after the U.S. approval of the
application and then annually until the study is completed or
terminated.

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 Center for Biologics Evaluation and
Research (CBER) and the Center for Drugs Evaluation and Research (CDER).
The application form serves primarily as a checklist for firms to gather
and submit to FDA. 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 FDA 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
(expires May 31, 2008.)

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 2253.
Form FDA 2253 (approved under OMB Control No. 0910-0001, expires May 31,
2008) was previously used only by drug manufacturers regulated by the
CDER. In August 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.

## Information Users

The PHS Act and FDA regulations require manufacturers to submit a
license application for review and approval prior to marketing a
biological product in interstate commerce. In addition, manufacturers
must submit to FDA advertising and promotional labeling. Manufacturers
are also required to submit changes, including labeling, changes to an
approved application, as well as advertising and promotional labeling
changes. The information submitted to FDA in a biologics license
application (BLA), supplement to an approved application, or other
similar submission is used to determine if a product is safe, effective,
and not misbranded under prescribed, recommended, or suggested
conditions of use. The recordkeeping requirements serve preventative and
remedial purposes to ensure safe use of the biological products. The
regulations also describe the types of postmarketing studies that
require status reports, the information to be included in the reports,
and the type of information that FDA would consider appropriate for
public disclosure. FDA use the information submitted from PMS reports to
meet its reporting obligations under section 506B of the act and section
130(b) of the Modernization Act. Without this and other information, FDA
could not monitor industry procedures and discharge its statutory
responsibility for protecting the nation's health.

## Improved Information Technology

One of FDA's continuing objectives is to improve the speed and quality
of its review and approval programs. In order to reach a decision to
approve an application, the agency must evaluate all information and
data provided by applicants on the safety, purity, potency, and efficacy
of the proposed product. To make the review process more efficient for
industry and FDA, CBER is utilizing electronic information systems
technology. CBER currently accepts the submission of electronic license
applications. FDA believes the increased use of computer-assisted
license applications will enhance the timeliness, effectiveness, and
efficiency of the review process and reduce burdensome, nonessential
hard-copy handling and storage. FDA is not aware of any other improved
technology to reduce the burden.

## Duplication of Similar Information

FDA is the only agency that requires the filing of an application for
the marketing of biological product for human use, any changes to an
approved application, and other required information. No other component
of FDA or other government agencies requires similar information or data
to be submitted. This information is not available from any other
source.

## Small Businesses

Although FDA must apply the statutory and regulatory requirements
equally to all enterprises, FDA does provide special help to small
businesses. The Center for Biologics Evaluation and Research (CBER),
Office of Communications, Training, and Manufacturers Assistance
provides assistance to small businesses subject to FDA's regulatory
requirements.

## Less Frequent Collection

Manufacturers are required to submit applications for approval of
biological products prior to marketing such products in interstate
commerce. In addition, manufacturers are required to submit a supplement
to an approved application prior to implementing a change or in an
annual report, depending on the significance of the change. Less
frequent collection of this and other information will not provide the
information that FDA needs to evaluate the safety, purity, potency, and
effectiveness of a biological product and properly monitor the progress
of PMSs.

There are no technical or legal obstacles to reducing the burden.

## Special Circumstances

An applicant may be required to submit to FDA proprietary trade secret
or other confidential information when submitting a license application,
change to an approved application, or an annual report. FDA has
instituted security measures to protect confidential information
received from manufacturers and will, to the extent permitted by law,
protect the information. In addition, certain changes to an approved
application are required to be submitted each time a change is made.
This information is necessary for FDA to ensure that the proposed
changes do not have an adverse effect on the strength, quality, purity,
or potency as they may relate to the safety and effectiveness of a
product.

## *Federal Register* Notice/Outside Consultation

In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice
requesting public comment on the information collection provisions in
the *Federal Register* on November 2, 2006 (71 FR 64536). No comments
were received from the public.

## Payment/Gift to Respondent

No payment or gift was provided to respondents.

## Confidentiality

The confidentiality of information received by FDA would be consistent
with the Freedom of Information Act and FDA's regulations under 21 CFR
Part 20, 21 CFR 601.51, and 601.70(e). Proprietary or trade secret
information is deleted from any information released by FDA under the
Freedom of Information Act and FDA regulations.

## Sensitive Questions

Questions of a sensitive nature are not applicable to this information
collection.

## Burden Estimate (Total Hours and Wages)

The total annual estimated burden imposed by this collection of
information is 335,807.5 hours annually.

Table 1. -- Estimated Annual Reporting Burden

  -------------------------- ----------- ------------- ----------- ----------- ---------- ---------
  21 CFR Section             Form FDA    No. of        Annual      Total       Hours per  Total
                             No.         Respondents   Frequency   Annual      Response   Hours
                                                       per         Responses              
                                                       Response                           

  601.2(a)^1^, 610.60,       2567/356h   14            2           28          860        24,080
  610.61, and 610.62^2^                                                                   

  601.5(a)                   NA          16            3.13        50          .33        17

  601.6(a)                   NA          1             21          21          .33        7

  601.12(a)(5)               NA          190           15.7        2,983       1          2,983

  601.12(b)(1)/(b)(3)^3^     356h^1^     190           4.75        903         80         72,240

  601.12(c)(1)/(c)(3)^4^     356h^1^     98            2.60        255         50         12,750

  601.12(c)(5)               356h^1^     34            1.38        47          50         2,350

  601.12(d)(1)/(d)(3)        356h^1^     166           1.37        227         22.5       5,107.5

  601.12(e)                  356h^1^     14            1.43        20          120        2,400

  601.12(f)(1)^5^            2567        12            1           12          40         480

  601.12(f)(2)^5^            2567        10            1           10          20         200

  601.12(f)(3)^6^            2567        70            1.43        100         10         1,000

  601.12(f)(4)/601.45        2567        15            36          540         10         5,400

  601.25(b)(3)               NA          0             0           0           0          0

  601.26(f)                  NA          0             0           0           0          0

  601.27(b)                  NA          3             1           3           24         72

  601.27(c)                  NA          7             1           7           8          56

  601.28(a), (b), and (c)    NA          44            3.27        144         33.5       4,824

  601.70(b) and (d)          2252        19            1.58        30          24         720

  601.91(b)(3), 601.94       NA          1             1           1           240        240

  610.67                     NA          174           31          5,400       24         129,600

  680.1(c)                   NA          10            1           10          2          20

  Amendments/Resubmissions   356h        306           11.6        3,563       20         71,260

  Total                                                                                   335,807
  -------------------------- ----------- ------------- ----------- ----------- ---------- ---------

^1^ The reporting requirements under §§ 601.14, 601.27(a), 601.33,
601.34, 601.35, 610.11(g)(2), 640.17, 640.25(c), 640.56(c),
640.74(b)(2), 660.51(a)(4), and 680.1(b)(2)(iii) are included in the
estimate under § 601.2(a).

^2^ The reporting requirements under §§ 640.70(a), 640.74(b)(3) and
(b)(4), 640.84(a) and (c), 640.94(a), 660.2(c), 660.28(a) and (b),
660.35(a), (c through g), and (i through m), 660.45, and 660.55(a) and
(b) are included under §§ 610.60 through 610.62.

^3^ The reporting requirements under §§ 600.15(b), 610.11(g)(2),
610.53(d), 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), and 680.1(d) are included in
the estimate under §§ 601.12(b).

^4^ The reporting requirements under §§ 640.17, 640.25(c), 640.56(c),
and 640.74(b)(2) are included in the estimate under §§ 601.12(c).

^5^ The reporting requirements under § 601.14 is included in the
estimates under §§ 601.12(f)(1) and (f)(2).

^6^ The reporting requirements under § 601.14 is included in the
estimates under 601.12(f)(3).

The number of respondents is based on the estimated annual number of
manufacturers that submitted the required information to FDA or the
number of submissions received. Based on information obtained from
FDA\'s database systems, there are an estimated 306 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) for a particular
product 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 §§ 601.2 and 601.12, the estimated hours per response are based on
the average number of hours to submit the various submissions. The
estimated average number of hours is based on the range of hours to
complete a very basic application or supplement and a complex
application or supplement.

Under § 601.6(a), the total annual responses are based on FDA estimates
that establishments may notify an average of 20 selling agents and
distributors of such suspension, and provide FDA of such notification.
The number of respondents is based on the estimated annual number of
suspensions of a biologic license.

Under §§ 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. Based on information obtained from FDA's database
system, there were an estimated 3,600 submissions of advertising and
promotional labeling in fiscal year 2004. FDA estimates that
approximately 15 percent of those submissions were received with Form
FDA 2567 resulting in an estimated 540 submissions. The burden hours for
the remaining submissions received using Form FDA 2253 are reported
under OMB Control No. 0910-0001.

Under § 601.70(b), FDA estimates that it takes an applicant
approximately 24 hours (8 hours per study x 3) annually to gather,
complete, and submit the appropriate information for each PMS report
(approximately two to four studies per report) and the accompanied
transmittal Form FDA 2252 (approved under OMB Control No. 0910-0001,
expires May 31, 2008). Included in these 24 hours is the time necessary
to prepare and submit two copies of the annual progress report of PMSs
to FDA under § 601.70(d).

Under §§ 601.91 through 601.94, FDA expects to receive very few
applications of this nature; however, for calculation purposes, FDA is
estimating the submission of one application annually. Under §§
601.91(b)(3) and 601.94, FDA estimates 240 hours for a manufacturer of a
new biological product to develop patient labeling, and to submit the
appropriate information and promotional labeling to FDA. The majority of
the burden for developing the patient labeling is included under the
reporting requirements for § 601.94, therefore minimal burden is
calculated for providing the guide to patients under § 601.91(b)(3).
Under § 601.93, any potential postmarketing reports and/or recordkeeping
burdens would be included under the adverse experience reporting (AER)
requirements under part 601 (21 CFR part 600) (OMB Control No.
0910-0308; expires July 31, 2008). Therefore, any burdens associated
with these requirements would be reported under the AER information
collection requirements.

There were also 3,540 amendments to an unapproved application or
supplement and 23 resubmissions (total of 3,563 submissions) submitted
using Form FDA 356h.

^Table\ 2.\ -\ Estimated\ Annual\ Recordkeeping\ Burden^

  ------------------- --------------- --------------- ----------- ----------- -----------
  21 CFR Section      No. of          Annual          Total       Hours per   Total Hours
                      Recordkeepers   Frequency per   Annual      Record      
                                      Recordkeeping   Records                 

  601.91(b)(2)(iii)   1               1               1           1           1
  ------------------- --------------- --------------- ----------- ----------- -----------

The estimated recordkeeping burden of 1 hour is based on previous
estimates for the recordkeeping requirements associated with the AER
system.

[Cost to Respondents]{.underline}

The estimated annual cost to respondents is \$14,105,571.

  ----------------- ----------------- ----------------- -----------------
  Activity          No. of Hours      Cost per Hour     Total Cost

  Reporting         335,806.5         \$42              \$14,103,873

  Reporting         24                \$69              \$1,656

  Recordkeeping     1                 \$42              \$42
  ----------------- ----------------- ----------------- -----------------

The cost estimate is based on a regulatory affairs specialist, at a pay
rate of \$42/hour, who would be responsible for filling out the form,
and preparing an application, supplement, PMS report, or other similar
submission, and recordkeeping. The cost estimate is also based on a
medical director at a pay rate of \$69/hour who would be responsible for
the preparing notification to FDA of discontinuance of a product(s), and
notification to industry of a license suspension (50 notices of
products(s) discontinuance and 21 notices of license suspension with an
average of 20 minutes per notification). The estimated average hourly
pay rate includes benefits but no overhead costs.

## Capital Costs (Maintenance of Capital Costs)

There are no capital costs or operating and maintenance costs associated
with this collection.

## Cost to Federal Government

The estimated annualized cost to FDA is \$15,920,432. This estimate is
based on full-time equivalents (FTEs) associated with the review of
license applications including supplemental applications or other
similar submissions, and PMS reports. The amount of time and expense
incurred by the Federal government is due to the review of all material
submitted with an application, supplement, or other similar submission,
and PMS reports. This information is essential to determine the safety
and effectiveness of products in support of FDA's mission to protect the
public health. This information may include clinical data, safety
updates, samples submitted for evaluation by the agency, case report
tabulations, case report forms, patient information, and PMS. In
addition, the estimate is based on the number of FTEs associated with
the processing of license revocations and suspensions, and advertising
and promotional labeling. The estimated average annual salary for CBER
reviewers is \$110,176 that includes benefits but no overhead costs.

  --------------------------- ------------- --------------------- --------------
  Activity                    Number of     Average Annual        Total Cost
                              FTEs          Reviewer Salary       

  Application/Supplement      103           \$110,176             \$11,348,128
  Review                                                          

  License Processing          36            \$110,176             \$3,966,336

  Advertisement/Promotional   4.5           \$110,176             \$495,792
  Labeling                                                        

  Review PMS Report           1             \$110,176             \$110,176

  Total                                                           \$15,920,432
  --------------------------- ------------- --------------------- --------------

## Program or Burden Changes

The burden estimate for 0910-0338 was 335,087.5. The slight increase in
burden to 335,807.5 is attributed to the consolidation of OMB packages:
0910-0433, and 0910-0530 (biologics regulations only).

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. Under § 601.25(b)(3), FDA estimates no
burden for this regulation since all requested data and information had
been submitted by 1974. Under section 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 § 601.12. Since there is no further
burden, we will no longer request OMB approval for these two
regulations.

## Publication and Tabulation Dates

There are no tabulated results to publish for this information
collection.

## Display of OMB Approval Date

FDA is not seeking approval to exempt the display of the expiration date
of the OMB approval.

## Exceptions to "Certification for Paperwork Reduction Act Submissions"

Not applicable.