**Supporting Statement**

**Environmental Impact Considerations - 21 CFR Part 25 ‑**

**(OMB Control Number 0910‑0322)**

**Docket \# 2006N-0105**

**Expires January, 2010**

A. **[Justification]{.underline}**

**1. [Circumstances of Information Collection]{.underline}**

FDA is requesting OMB approval for the reporting requirements contained
in the FDA regulation "Environmental Impact Considerations."

The National Environmental Policy Act (NEPA), 42 U.S.C. 4321-4347,
states national environmental objectives and imposes upon each Federal
agency the duty to consider the environmental effects of its actions.
Section 102(2)(C) of NEPA requires the preparation of an environmental
impact statement (EIS) for every major Federal action that will
significantly affect the quality of the human environment.

The FDA NEPA regulations are at 21 CFR part 25. All applications or
petitions requesting agency action require the submission of a claim for
a categorical exclusion or an environmental assessment (EA). A
categorical exclusion applies to certain classes of FDA-regulated
actions that usually have little or no potential to cause significant
environmental effects and are excluded from the requirements to prepare
an EA or EIS. Section 25.15(a) and (d) specifies the procedures for
submitting to FDA a claim for a categorical exclusion. Extraordinary
circumstances (§ 25.21), which may result in significant environmental
impacts, may exist for some actions that are usually categorically
excluded. An EA provides information that is used to determine whether
an FDA action could result in a significant environmental impact.
Sections 25.40(a) and (c) specifies the content requirements for EAs for
nonexcluded actions.

This collection of information is used by FDA to assess the
environmental impact of agency actions and to ensure that the public is
informed of environmental analyses. Firms wishing to manufacture and
market substances regulated under statutes for which FDA is responsible
must, in most instances, submit applications requesting approval.
Environmental information must be included in such applications for the
purpose of determining whether the proposed action may have a
significant impact on the environment. Where significant adverse effects
cannot be avoided, the agency uses the submitted information as the
basis for preparing and circulating to the public an EIS, made available
through a [Federal Register]{.underline} document also filed for comment
at the Environmental Protection Agency (EPA). The final EIS, including
the comments received, is reviewed by the agency to weigh environmental
costs and benefits in determining whether to pursue the proposed action
or some alternative that would reduce expected environmental impact. Any
final EIS would contain additional information gathered by the agency
after the publication of the draft EIS, a copy of or a summary of the
comments received on the draft EIS, and the agency=s responses to the
comments, including any revisions resulting from the comments or other
information. When the agency finds that no significant environmental
effects are expected, the agency prepares a finding of no significant
impact (FONSI).

**2. [Purpose and Use of Information]{.underline}**

This collection of information is used by FDA to assess the
environmental impact of agency actions and to ensure that the public is
informed of environmental analyses. Firms wishing to manufacture and
market substances regulated under statutes for which FDA is responsible
must, in most instances, submit applications requesting approval.
Environmental information must be included in such applications for the
purpose of determining whether the proposed action may have a
significant impact on the environment. Where significant adverse effects
cannot be avoided, the agency uses the submitted information as the
basis for preparing and circulating to the public an EIS, made available
through a Federal Register notices also filed for comment at the
Environmental Protection Agency (EPA). If the agency finds that no
significant environmental effects are expected, the agency prepares a
finding of no significant impact (FONSI).

**3. [Use of Improved Information Technology]{.underline}**

For human drugs, the submissions under 21 CFR part 25 are part of an
application for marketing. Some of the steps that FDA has taken to
facilitate the electronic submission of marketing applications include:

In the [Federal Register]{.underline} of December 11, 2003, FDA issued a
final rule amending FDA regulations governing the format in which
certain labeling is required to be submitted for review with NDAs,
certain BLAs, ANDAs, supplements, and annual reports. The final rule
requires the electronic submission of the content of labeling (i.e., the
content of the package insert or professional labeling, including all
text, tables, and figures) in NDAs, certain BLAs, ANDAs, supplements,
and annual reports electronically in a form that FDA can process,
review, and archive.

The following guidances for industry are among those that have been
developed to improve the use of information technology in the submission
of marketing applications for human drugs and related reports:

-   \"Providing Regulatory Submissions in Electronic

Format\--NDAs\" (January 28, 1999). This guidance provides information
on how to submit a complete archival copy of an NDA in electronic format
and applies to the submission of original NDAs as well as to the
submission of supplements and amendments to NDAs.

-   \"Providing Regulatory Submissions in Electronic

Format\--General Considerations\" (January 28, 1999). This guidance
includes a description of the types of electronic file formats that the
agency is able to accept to process, review, and archive electronic
documents. The guidance also states that documents submitted in
electronic format should enable the user to: (1) Easily view a clear and
legible copy of the information; (2) print each document page by page
while maintaining fonts, special orientations, table formats, and page
numbers; and (3) copy text and images electronically into common word
processing documents.

-   "Providing Regulatory Submissions to the Center for

Biologics Evaluation and Research (CBER) in Electronic Format" (November
12, 1999). This guidance provides information to assist applicants in
submitting documents in electronic format for review and archive
purposes as part of a BLA, product license application (PLA), or
establishment license application (ELA).

**•** \"Providing Regulatory Submissions in Electronic
Format----Prescription Drug Advertising and Promotional Labeling\"
(January 31, 2001). This draft guidance discusses issues related to the
electronic submission of advertising and promotional labeling materials
for prescription drug and biological products.

**•** \"Providing Regulatory Submissions in Electronic Format----ANDAs\"
(June 27, 2002). This guidance discusses issues related to the
electronic submission of ANDAs and supplements and amendments to those
applications.

**•** \"Providing Regulatory Submissions in Electronic Format----Annual
reports for NDAs and ANDAs\" (August 2003). This guidance discusses
issues related to the electronic submission of annual reports for NDAs
and ANDAs.

**•** \"Providing Regulatory Submissions in Electronic
Format----Postmarketing Periodic Adverse Drug Experience Reports\" (June
2003). This guidance discusses general issues related the electronic
submission of postmarketing periodic adverse drug experience reports for
NDAs, ANDAs, and BLAs.

**•** \"Providing Regulatory Submissions in Electronic Format----Human
Pharmaceutical Product Applications and Related Submissions\" (August,
2003). This draft guidance discusses issues related to the electronic
submission of ANDAs, BLAs, INDs, NDAs, master files, advertising
material, and promotional material.

**•** \"Providing Regulatory Submissions in Electronic Format----General
Considerations\" (October 2003). This draft guidance discusses general
issues common to all types of electronic regulatory submissions.

**•** \"Providing Regulatory Submissions in Electronic Format----Content
of Labeling\" (February 2004). This draft guidance discusses issues
related to the submission of the content of labeling in electronic
format for marketing applications for human drug and biological
products.

These guidance documents are available at FDA\'s web

site <http://www.fda.gov/cder/guidance/index.htm>[.]{.underline}

**4. [Efforts to Identify Duplication]{.underline}**

FDA avoids duplication by encouraging applicants to reference in their
environmental documents data and information presented in other
documents that are available to FDA and the public (21 CFR 25.40(d)).
FDA intends to focus environmental reviews on the use and disposal from
use of FDA regulated articles. Because FDA actively works to ensure the
consistency of its protocols with those prescribed by EPA, the American
Society for Testing and Materials (ASTM), and Organization for Economic
Co-operation and Development (OECD), FDA avoids unnecessary duplication
of environmental testing. Thus, environmental testing that has already
been performed will not have to be repeated by a different protocol when
applicants move from one regulatory agency to another and from one
country to another for approvals of the same chemical substance.

Where possible, existing data are used by FDA in evaluating the
environmental impact of an industry-sponsored application or petition.
To the extent publicly available, data in FDA files may be
cross-referenced, data available in the scientific literature may be
submitted, and data gathered for other government agencies, such as EPA,
may be used in support of the environmental review of an application to
FDA.

FDA recognizes that there are instances where the same substance may be
the subject of separate environmental analyses by another agency, for
example by EPA. FDA has determined that separate environmental review is
not necessary for FDA approval of a food additive petition or FDA
granting a request for an exemption from regulations as a food additive
if the substance is already registered by EPA under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) for the same use
requested in the petition. Although both agencies have worked to
eliminate duplication of effort, applications submitted to FDA sometimes
involve a different use of a chemical substance than the use(s) reviewed
by EPA and the patterns of environmental introduction often vary.
Therefore, in some circumstances, a document prepared by FDA or another
agency may not suffice as the NEPA document.

**5. [Involvement of Small Entities]{.underline}**

For both large and small entities, FDA has identified the types of
information necessary to review the environmental impact of a new
product and, where possible, provides case-by case guidance on the
specific types of information required for a particular action. FDA does
not have the resources to perform a firm=s environmental studies and the
information gathering necessary for the evaluation of a new product.
However, small manufacturers may request help in applying for approval
from the FDA office that works with small manufacturers. Because FDA has
identified categories of actions that are categorically excluded from
the requirement to prepare an EA and EIS, fewer EA\'s and EIS\'s are
likely to be required from small businesses.

**6. [Consequences If Information Collected Less
Frequently]{.underline}**

Industry-sponsored applications and petitions are submitted to obtain
permission to market a new product or to expand the usage of a currently
regulated product. If the frequency of collection for environmental
impact data were reduced, the agency could not assess the environmental
impact of approving applications. Failure to take environmental factors
into account in the agency decision making would leave the agency
susceptible to court challenge and may result in unnecessary delays in
the approval for marketing of products.

**7. [Consistencies with Guidelines in 5 CFR 1320.5(d)(2)]{.underline}**

Data collection for applications is consistent with these guidelines.

**8. [Consultations Outside the Agency]{.underline}**

In the [Federal Register]{.underline} of March 29, 2006 (71 FR 15753),
FDA requested comments on the proposed collection of information. FDA
received one comment. The comment said it supports the current FDA
approach to assessing potential environmental impact under NEPA.
However, the comment questioned whether one aspect of the collection of
information is necessary for the proper performance of FDA\'s functions,
including whether the information has practical utility, and contended
that eliminating the collection of information would minimize the burden
on respondents.

Specifically, the comment suggested that FDA should "eliminate
unnecessary work" related to requests for categorical exclusions for
actions on certain INDs. Section 25.31 lists classes of actions that are
categorically excluded and, therefore, ordinarily do not require the
preparation of an EA or an EIS. Section 25.31(e) lists an "action on an
IND" as one of these classes of actions. The comment proposed that §
25.31(e) be amended as follows: "Action on INDs where the drug or
biologic product is derived from wild plants or animals. Action on other
types of INDs do not require a claim for a categorical exclusion." The
comment proposed that categorical exclusions should be automatically
granted for actions on INDs where the drug or biologic products are not
derived from wild plants or animals.

The comment proposed this amendment to § 25.31(e) for the following
reasons, each of which suggests that claims for categorical exclusion
for action on an IND have little practical utility and amending §
25.31(e) as proposed represents a way to minimize the burden of the
collection of information:

\(1\) FDA's guidance document entitled \"Environmental Assessment of
Human Drug and Biologics Applications\" (July 1998) states:

> \"INDs generally involve relatively small quantities of a drug or
> biologic product and treatment of a limited number of patients. Many
> INDs never result in the filing of an NDA or application for marketing
> approval of a biologic product, which would allow for the wide-spread
> commercial sale of the product. CDER and CBER will evaluate INDs on a
> case-by-case basis where the drug or biologic product is derived from
> wild plants or animals to determine whether the extraordinary
> circumstance provision in 21 CFR 25.21 is invoked.\" (Section
> III.C.3.b.ii of the guidance document).

\(2\) Pharmaceutical companies have been providing claims for
categorical exclusion for action on an IND since the early 1990\'s for
active pharmaceutical ingredients (APIs) in all therapeutic classes, and
the companies have no indication that FDA has used these claims as the
basis for denials pertinent to potential environmental impact as
described under NEPA.

\(3\) Usage of an API under an IND is "site limited and time bounded,"
indicating that "the potential for patient excretion of an API to the
environment is extremely limited."

\(4\) The potential risk from pharmaceuticals in the environment
pertains to long-term, chronic exposure, and usage of an API under an
IND will not result in the type of exposure widely accepted as being of
potential environmental concern. The comment also stated that prior to
marketing approval of an API, FDA will have the opportunity to review
potential environmental impact through its EA requirements.

\(5\) The comment concluded that amending § 25.31(e) as proposed would
have "eliminated work on up to 1933 categorical exclusions (15,464
hours) for INDs in 2005 that ultimately had no practical utility.\"

FDA appreciates the comment requesting that § 25.31(e) be amended so
that categorical exclusions could be automatically granted for actions
on INDs where the drug or biologic products are not derived from wild
plants or animals. The purpose of the March 29, 2006, [Federal
Register]{.underline} notice and this notice, however, is to afford an
opportunity for comment on the information collection requirements and
burden estimates for part 25, and to request that OMB extend approval
for that collection. Because the comment requests a rulemaking change,
we have forwarded it to the office in each Center that is responsible
for the information collection requirements in part 25 so that the
comment may be considered for any future amendments to the regulations.

**9. [Remuneration of Respondents]{.underline}**

FDA has not provided and has no intention to provide any payment or gift
to respondents under the revisions of part 25.

**10. [Assurance of Confidentiality]{.underline}**

NEPA requires that EA\'s and EIS\'s be made available for public review.
However, 21 CFR 25.50(b) recognizes that FDA actions involving
investigations, review, and approval of applications and premarket
notifications for human drugs, animal drugs, biologic products, and
devices are protected from disclosure under the Trade Secret Act (TSA),
the Federal Food, Drug, and Cosmetic Act (FFDCA), and 21 CFR part 20.
Additionally, under 21 CFR 25.51 (a), data constituting trade secrets or
confidential information under the TSA or the FFDCA must not be included
in the portion of environmental documents that is made public. Thus,
environmental information will be made available to the public to the
extent permitted.

**11. [Questions of a Sensitive Nature]{.underline}**

There are no questions of a sensitive nature in the environmental impact
requirements.

**12. [Estimates of Annualized Hour Burden]{.underline}**

[Estimated annual reporting burden for human drugs]{.underline}

Under 21 CFR 312.23(a)(7)(iv)(*e*), 21 CFR 314.50(d)(1)(iii), and 21 CFR
314.94(a)(9)(i), each investigational new drug application (IND), new
drug application (NDA), and abbreviated new drug application (ANDA) must
contain a claim for categorical exclusion under \'\' 25.30 or 25.31 or
an EA under \' 25.40. In 2005, FDA received 1,933 INDs from 1,517
sponsors, 114 NDAs from 94 applicants, 2,682 supplements to NDAs from
293 applicants, 777 ANDAs from 161 applicants, and 4,318 supplements to
ANDAs from 219 applicants. FDA estimates that it receives approximately
9,813 claims for categorical exclusions as required under \'\' 25.15(a)
and (d), and 11 EAs as required under \'\' 25.40(a) and (c). Based on
information provided by the pharmaceutical industry, FDA estimates that
it takes sponsors or applicants approximately 8 hours to prepare a claim
for a categorical exclusion and approximately 3,400 hours to prepare an
EA.

+---------+-------------+-----------+-----------+----------+----------+
| Es      |             |           |           |          |          |
| timated |             |           |           |          |          |
| Annual  |             |           |           |          |          |
| Re      |             |           |           |          |          |
| porting |             |           |           |          |          |
| Burden  |             |           |           |          |          |
| for     |             |           |           |          |          |
| Human   |             |           |           |          |          |
| Drugs   |             |           |           |          |          |
+=========+=============+===========+===========+==========+==========+
| CFR     | Number of   | Annual    | Total     | Hours    | Total    |
|         | Respondents | Frequency | Annual    |          | Burden   |
| Section |             | per       | Responses | per      | Hours    |
|         |             | Response  |           | Response |          |
+---------+-------------+-----------+-----------+----------+----------+
| 25.15   | 2,284       | 4.32      | 9,813     | 8        | 78,504   |
|         |             |           |           |          |          |
| (a)&(d) |             |           |           |          |          |
+---------+-------------+-----------+-----------+----------+----------+
| 25.40   | 11          | 1         | 11        | 3,400    | 37,400   |
|         |             |           |           |          |          |
| (a)&(c) |             |           |           |          |          |
+---------+-------------+-----------+-----------+----------+----------+
| Total   |             |           |           |          | 115,904  |
+---------+-------------+-----------+-----------+----------+----------+

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

[Estimated annual reporting burden for human foods]{.underline}

Under 21 CFR 71.1, 171.1, 170.39, and 170.100, food additive petitions,
color additive petitions, requests for exemption from regulation as a
food additive, and submission of a food contact notification (FCN) for a
food contact substance must contain either a claim of categorical
exclusion under \'\' 25.30 or 25.32, or an EA under \' 25.40. From 2003
to 2005, FDA received an annual average of 88 industry submissions. FDA
estimates that it received an annual average of 57 claims of categorical
exclusions as required under \'\' 25.15(a) and (d), and 31 EAs as
required under \'\' 25.40(a) and (c). FDA estimates that, on average, it
takes petitioners, notifiers, or requestors approximately 3 hours to
prepare a claim of categorical exclusion and approximately 210 hours to
prepare an EA.

+--------+-------------+-----------+-----------+-----------+-----------+
| Est    |             |           |           |           |           |
| imated |             |           |           |           |           |
| Annual |             |           |           |           |           |
| Rep    |             |           |           |           |           |
| orting |             |           |           |           |           |
| Burden |             |           |           |           |           |
| for    |             |           |           |           |           |
| Human  |             |           |           |           |           |
| Foods  |             |           |           |           |           |
+========+=============+===========+===========+===========+===========+
| CFR    | Number of   | Annual    | Total     | Hours per | Total     |
|        | Respondents | Frequency | Annual    | Response  | Burden    |
| S      |             | per       | Responses |           | Hours     |
| ection |             | Response  |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.15  | 57          | 1.4       | 80        | 3         | 240       |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(d) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.40  | 31          | 1.3       | 39        | 210       | 8,190     |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(c) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| Total  |             |           |           |           | 8,430     |
+--------+-------------+-----------+-----------+-----------+-----------+

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

[Estimated annual reporting burden for medical devices]{.underline}

Under 21 CFR 814.20(b)(11), pre-market approvals (original PMAs and
supplements) must contain a claim for categorical exclusion under \'\'
25.30 or 25.34 or an environmental assessment under \' 25.40. In 2005,
FDA received 282 claims (original PMAs and supplements) for categorical
exclusions as required under \'\' 25.15(a) and (d), and 0 EAs as
required under \'\' 25.40(a) and (c). Based on information provided by
less than 10 sponsors, FDA estimates that it takes approximately less
than 1 hour to prepare a claim for a categorical exclusion and an
unknown number of hours to prepare an EA.

+--------+-------------+-----------+-----------+-----------+-----------+
| Est    |             |           |           |           |           |
| imated |             |           |           |           |           |
| Annual |             |           |           |           |           |
| Rep    |             |           |           |           |           |
| orting |             |           |           |           |           |
| Burden |             |           |           |           |           |
| for    |             |           |           |           |           |
| M      |             |           |           |           |           |
| edical |             |           |           |           |           |
| D      |             |           |           |           |           |
| evices |             |           |           |           |           |
+========+=============+===========+===========+===========+===========+
| CFR    | Number of   | Annual    | Total     | Hours per | Total     |
|        | Respondents | Frequency | Annual    | Response  | Burden    |
| S      |             | per       | Responses |           | Hours     |
| ection |             | Response  |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.15  | 47          | 6         | 282       | 1         | 282       |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(d) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.40  | 0           | 0         | 0         | 0         | 0         |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(c) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| Total  |             |           |           |           | 282       |
+--------+-------------+-----------+-----------+-----------+-----------+

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

[Estimated annual reporting burden for biological products]{.underline}

Under 21 CFR 312.23(a)(7)(iv)(e) and 601.2(a), IND and biologics license
applications (BLAs) must contain a claim for categorical exclusion under
\'\' 25.30 or 25.31 or an EA under \' 25.40. In 2005, FDA received 565
INDs from 426 sponsors, 27 BLAs from 12 applicants, and 737 BLA
supplements to license applications from 205 applicants. FDA estimates
that approximately 10 percent of these supplements would be submitted
with a claim for categorical exclusion or an EA.

FDA estimates that it received approximately 666 claims for categorical
exclusion as required under \'\' 25.15(a) and (d), and [2]{.underline}
EAs as required under \'\' 25.40(a) and (c). Based on information
provided by industry, FDA estimates that it takes sponsors and
applicants approximately 8 hours to prepare a claim for categorical
exclusion and approximately 3,400 hours to prepare an EA for a
biological product.

+--------+-------------+-----------+-----------+-----------+-----------+
| Est    |             |           |           |           |           |
| imated |             |           |           |           |           |
| Annual |             |           |           |           |           |
| Rep    |             |           |           |           |           |
| orting |             |           |           |           |           |
| Burden |             |           |           |           |           |
| for    |             |           |           |           |           |
| Biol   |             |           |           |           |           |
| ogical |             |           |           |           |           |
| Pr     |             |           |           |           |           |
| oducts |             |           |           |           |           |
+========+=============+===========+===========+===========+===========+
| CFR    | Number of   | Annual    | Total     | Hours per | Total     |
|        | Respondents | Frequency | Annual    | Response  | Burden    |
| S      |             | per       | Responses |           | Hours     |
| ection |             | Response  |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.15  | 459         | 1.45      | 666       | 8         | 5,328     |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(d) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.40  | 2           | 1         | 2         | 3,400     | 6,800     |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(c) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| Total  |             |           |           |           | 12,128    |
+--------+-------------+-----------+-----------+-----------+-----------+

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

[Estimated annual reporting burden for animal drugs]{.underline}

Under 21 CFR \' 514.1(b)(14) (21 CFR 514.1(b)(14)), new animal drug
applications (NADAs) and abbreviated new animal drug applications
(ANADA=s), \' 514.8(a)(1) supplemental NADAs and ANADAs, \' 511.1
(b)(10) investigational new animal drug applications (INADs), \' 570.35
(c)(1)(viii) generally recognized as safe (GRAS) affirmation petitions,
and \' 571.1(c) food additive petitions must contain a claim for
categorical exclusion under \'\' 25.30 or 25.33 or an EA under \' 25.40.
In 2005, FDA's Center for Veterinary Medicine (CVM) has received
approximately 421 claims for categorical exclusion as required under
\'\' 25.15(a) and (d), and 14 EAs as required under \'\' 25.40(a) and
(c). Based on information provided by industry, FDA estimates that it
takes sponsors/applicants approximately 8 hours to prepare a claim for a
categorical exclusion and an average of 2,160 hours to prepare an EA.

+--------+-------------+-----------+-----------+-----------+-----------+
| Est    |             |           |           |           |           |
| imated |             |           |           |           |           |
| Annual |             |           |           |           |           |
| Rep    |             |           |           |           |           |
| orting |             |           |           |           |           |
| Burden |             |           |           |           |           |
| for    |             |           |           |           |           |
| Animal |             |           |           |           |           |
| Drugs  |             |           |           |           |           |
+========+=============+===========+===========+===========+===========+
| CFR    | Number of   | Annual    | Total     | Hours per | Total     |
|        | Respondents | Frequency | Annual    | Response  | Burden    |
| S      |             | per       | Responses |           | Hours     |
| ection |             | Response  |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.15  | 135         | 3.9       | 421       | 8         | 3,368     |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(d) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| 25.40  | 12          | 1.6       | 14        | 2,160     | 30,240    |
|        |             |           |           |           |           |
| (      |             |           |           |           |           |
| a)&(c) |             |           |           |           |           |
+--------+-------------+-----------+-----------+-----------+-----------+
| Total  |             |           |           |           | 33,608    |
+--------+-------------+-----------+-----------+-----------+-----------+

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

  ---------------------------------------------------------------------------
  **Combined                                                      
  Estimated                                                       
  Annual Total                                                    
  Burden Hours                                                    
  for All                                                         
  Centers**                                                       
  ------------ -------------- ----------- ----------- ----------- -----------
  Total                                                           170,352

  ---------------------------------------------------------------------------

**13. [Estimates of Annualized Cost Burden to Respondents]{.underline}**

FDA\'s Economics Staff estimates the average industry wage rate of
\$50.00 per hour for preparing and submitting the information collection
requirements associated with marketing applications. Based on a total
industry burden of 170,352 hours, the annualized cost burden to
respondents would be \$8,517,600.

**14. [Estimates of Annualized Cost Burden to the
Government]{.underline}**

FDA estimates that a total of approximately 8 FTEs are devoted to the
review of submissions associated with 21 CFR part 25. Based on an
estimate of \$250,000 per FTE, the annualized cost burden to FDA would
be approximately \$2,000,000.

**15. [Changes in Burden]{.underline}**

The revised burden estimates are the result of the number of claims for
categorical exclusions and EAs submitted mainly during 2004-2005.

**16. [Time Schedule, Publication, and Analysis Plans]{.underline}**

FDA does not intend to publish tabulated results of the information
collection requirements that are imposed by 21 CFR part 25.

**17. [Displaying of OMB Approval Date]{.underline}**

> There are no forms associated with this collection.

**18. [Exception to the Certification Statement - Item 19]{.underline}**

There are no exceptions to the \"Certification for Paperwork Reduction
Act Submissions\" in item 19 of OMB Form 83-I.