**SUPPORTING STATEMENT**

Requirements for Submission of Labeling for Human Prescription Drugs and
Biologics in Electronic Format

OMB Number 0910-0530

Docket Number 00N-1652

A. [Justification]{.underline}

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

This information collection approval request is for a Food and Drug
Administration (FDA) final rule amending FDA regulations governing the
format in which certain labeling is required to be submitted for review
with new drug applications (NDAs), certain biological license
applications (BLAs), abbreviated new drug applications (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
form that FDA can accept for processing, reviewing, and archiving under
the final rule is portable document format (PDF). The requirement to
submit the content of labeling electronically is in addition to existing
requirements that copies of the label and labeling and specimens of
enclosures be submitted.

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

Each year FDA conducts a word-for-word comparison as part of the review
process for more than 1,000 proposed labeling changes for approved NDAs
and BLAs, and more than 2,600 proposed original and supplemental
labeling changes for ANDAs. Because reviewers currently conduct these
comparisons manually using two paper copies of the labeling, the process
is slow and subject to error. Requiring the electronic submission of
labeling for NDAs, certain BLAs, ANDAs, supplements, and annual reports
will greatly enhance the accuracy and speed of labeling review. This
will result in increased protection of the public health because
electronic review and comparison of labeling files will provide a higher
degree of certainty that all sections of prescription drug labeling are
correct.

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

Although FDA has not previously required regulatory submissions in
electronic format, the agency has issued several guidances describing
how to make voluntary electronic submissions to the agency. In January
1999, FDA issued a guidance on general considerations for electronic
submissions entitled "Providing Regulatory Submissions in Electronic
Format\--General Considerations." The general considerations guidance
included a description of the types of electronic file formats that we
are able to accept for processing, reviewing, and archiving electronic
documents. In January, 1999, FDA announced the availability of a
guidance entitled "Providing Regulatory Submissions in Electronic
Format\--NDAs," which provided information on how to submit a complete
archival copy of an NDA in electronic format. In November 1999, FDA
published a guidance 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). Most recently, FDA published a guidance for ANDAs, "Providing
Regulatory Submission in Electronic Format---ANDAs" (June 27, 2002), and
"Providing Regulatory Submission in Electronic Format--- Annual Reports
for NDAs and ANDAs\" (August 2003).

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

The requirement to submit the content of labeling electronically is in
addition to existing requirements that copies of the label and labeling
and specimens of enclosures be submitted. However, requiring the
electronic submission of the content of labeling will greatly enhance
the accuracy and speed of labeling review by FDA. This will result in
increased protection of the public health because electronic review and
comparison of labeling files will provide a higher degree of certainty
that all sections of prescription drug labeling are correct.

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

Although new drug development is typically an activity completed by
large multinational drug firms, the information collection requested
under the guidance applies to small as well as large companies. Under
the Regulatory Flexibility Act, FDA regularly analyzes regulatory
options that would minimize any significant impact on small entities.
FDA also assists small businesses in complying with regulatory
requirements.

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

The content of labeling is required to be submitted electronically for
review with NDAs, certain BLAs, ANDAs, supplements, and annual reports.
FDA\'s review of labeling is an integral part of its approval of
marketing application for drugs and biologics. The labeling must be
consistent with the approved conditions for marketing.

7\. [Consistency with the Guidelines in 5 CFR 1320.5(d)(2)]{.underline}

There is no inconsistency resulting from this final rule.

8\. [Consultation Outside the Agency]{.underline}

FDA received thirteen sets of written comments on the May 3, 2002,
proposed rule from manufacturers, trade associations, advocacy groups,
consulting firms, and individuals. The majority of the comments
supported FDA's proposal to require that the content of certain labeling
be submitted electronically in a form that FDA can process, review, and
archive. A few comments requested clarification on various aspects of
the rule, and one comment opposed the exemptions from specific controls
under part 11. The final rule contains a summary of the comments
received and the agency's responses.

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

FDA has not provided and has no intention to provide any payment or gift
to respondents under this guidance.

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

Confidentiality of the information submitted under these regulations is
protected under 21 CFR 314.430, 21 CFR 601, and 21 CFR part 20. The
unauthorized use or disclosure of trade secrets required in applications
is specifically prohibited under Section 310(j) of the Act.

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

There are no questions of a sensitive nature.

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

Copies of product labeling are currently required to be submitted to FDA
for review in NDAs, certain BLAs, ANDAs, certain supplements, and annual
reports under §§ 314.50, 314.70, 314.81, 314.94, 314.97, 314.98, 601.2,
and 601.12. Copies of labeling may be submitted electronically or on
paper. The final rule is adding the new requirements because submitting
the content of labeling in electronic format will simplify the drug
labeling review process and speed up the approval of labeling changes.

As required under section 3506 (c)(2)(B) of the Paperwork Reduction Act,
FDA provided an opportunity for public comments on May 3, 2002 (67 FR
22367), on the information collection provisions of the proposed rule.
FDA received two comments stating that the agency underestimated the
time and costs to prepare the content of labeling in electronic format
for submission to FDA. Specifically, the comments stated that the 15
minutes to convert the labeling into PDF was underestimated because it
did not take into account the time needed to proofread the content of
labeling document.

FDA believes that proofreading is not an additional cost for submitting
labeling in electronic format for new submissions of NDAs, BLAs, and
ANDAs. Labeling is proofread prior to submission regardless of the
format. If the labeling is in a word processing file, it is irrelevant
whether the document is printed or converted to a PDF file. This is
because the finished product, the labeling, is proofread for quality
assurance in either case. In addition, someone may need even less time
to proofread an electronic file than a printed document because the
computer could assist in finding errors. As such, the burden estimate
for these applications in the final rule has not been changed.

However, the revised estimates do allow for proofreading of labeling
under certain circumstances. Applicants that have previously submitted
labeling in paper format in annual reports or supplements, but also
maintained the labeling document in electronic format, should be
provided time for proofreading the converted file. This category of
labeling would not require any changes to the labeling since it was last
submitted to the agency. It only requires additional time for
proofreading to ensure that the electronic document being submitted is
the same as the labeling previously submitted in paper format. The hours
per response (i.e., the time it will take an applicant to submit the
labeling content electronically for these annual reports and
supplements) is approximately 5 hours.

As noted in the proposed rule, some older annual reports may require
additional steps, such as accessing the labeling in the archives,
putting the content of labeling into an electronic format, and
converting it to a PDF file. In response to the proofreading comments
mentioned above, an additional 2 hours is estimated for proofreading
this type of labeling (the proposed rule allowed for 8 hours and the
final rule is allowing for 10 hours).

[Current OMB approval of labeling information collection:]{.underline}
The reporting burdens for submitting labeling as currently required
under §§ 314.50(e)(2)(ii); 314.70(b)(3),(c)(2), and (d)(2) and (3);
314.81(b)(2)(iii), 314.94(a)(8), 314.97, and 314.98 have previously been
estimated by FDA, and this collection of information was approved by OMB
until March 31, 2005, under OMB control number 0910-0001. The reporting
burdens associated with current §§ 601.2 and 601.12 have also previously
been estimated, and this collection of information was approved by OMB
until August 31, 2005, under OMB control number 0910-0338 (including the
collection of information previously submitted under OMB control number
0910-0315). This analysis does not reestimate these approved burdens.
Only the additional reporting burdens associated with the electronic
submission of the content of labeling are estimated.

[New NDAs (§ 314.50), ANDAs (§ 314.94), and BLAs (§ 601.2]{.underline}):
Based on data in the approved collections of information for §§ 314.50,
314.94, and 601.2, approximately 83 NDA applicants, 117 ANDA applicants,
and 17 BLA applicants submit applications annually. These applicants
will submit approximately 85 NDAs, 323 ANDAs, and 17 BLAs each year that
will be subject to this rule.[^1] Based on the agency\'s experience with
voluntary electronic submissions and its knowledge of the drug and
biologic industries, it is assumed that applicants for new NDAs, ANDAs,
and BLAs will already have the necessary labeling in an electronic
format that can be easily accessed and converted to a PDF file. Thus,
the hours per response, i.e., the additional time necessary for
submission of the content of labeling in electronic format for these
applications, will be less than 15 minutes. Therefore, respondents will
spend approximately 106 hours per year submitting the content of
labeling in accordance with the final rule.

[Supplements to NDAs (§ 314.70) and ANDAs (§ 314.97) and BLAs (§
601.12(f)(1) and (f)(2))]{.underline}: Based on data in the approved
collections of information for §§ 314.70, 314.97, and 601.12(f)(1) and
(f)(2), approximately 418 NDA applicants, 152 ANDA applicants, and 20
BLA applicants submit supplements to approved applications annually.
These applicants will submit approximately 630 NDA supplements, 1,000
ANDA supplements, and 20 BLA supplements each year that will be subject
to this rule.

Based on the agency\'s experience with voluntary electronic submissions
and its knowledge of the drug and biologic industries, it is assumed
that approximately 254 NDA supplements, 396 ANDA supplements, and 10 BLA
will be submitted by applicants who already have the necessary labeling
in an electronic format that can be easily accessed and converted to a
PDF file. Thus, the hours per response, i.e., the additional time
necessary for submission of the content of labeling in electronic format
for these supplements, will be less than 15 minutes. Therefore,
respondents will spend approximately 165 hours per year submitting the
content of labeling in these supplements under the final rule.

As mentioned previously, a new category has been added to allow for
proofreading the converted file of labeling that was previously
submitted in supplements in paper form (and not requiring any changes
since it was last submitted), but is also maintained by the applicant in
an electronic format. Approximately 376 NDA supplements, 604 ANDA
supplements, and 10 BLA supplements will be submitted by applicants who
previously submitted labeling in paper, but have such labeling available
in electronic format. The hours per response, i.e., the time it will
take an applicant to submit the labeling content electronically for
these supplements, will be approximately 5 hours. Therefore, in the
first year, respondents will spend approximately 4,950 hours submitting
the content of labeling that was previously submitted in supplements in
paper form. For all supplements combined, in the first year, respondents
will spend approximately 5,115 hours submitting the content of labeling
in supplements under the final rule. This expenditure of time will only
be necessary the first time that a supplement is submitted with the
content of labeling in electronic format. Once the content of labeling
has been converted to an electronic format, the time necessary to submit
the content of labeling in subsequent supplements will be the same as
that for the other types of submissions, or less than 15 minutes.
Therefore, in subsequent years, respondents will spend approximately 413
hours per year submitting the content of labeling in supplements.

[Annual Reports for NDAs (§ 314.81), ANDAs (§ 314.98), and BLAs (§
601.12(f)(3))]{.underline}: Based on data in the approved collections of
information for §§ 314.81, 314.98, and 601.12(f)(3), approximately 275
NDA applicants, 275 ANDA applicants, and 75 BLA applicants submit annual
reports annually. Each NDA applicant submits approximately 9.45 annual
reports, each ANDA applicant submits approximately 16.18 annual reports,
and each BLA applicant submits approximately 1 annual report each year.
Further, the total annual responses, i.e., the total number of annual
reports submitted per year, will remain approximately 2,600 NDA annual
reports, 4,450 ANDA annual reports, and 75 BLA annual reports.

Based on the agency\'s experience with voluntary electronic submissions
and its knowledge of the drug and biologic industries, it is estimated
that approximately 24 percent of NDA annual reports (624 NDA annual
reports), 20 percent of ANDA annual reports (890 ANDA annual reports),
and 24 percent of BLA annual reports (18 BLA annual reports), will
already have the necessary labeling in an electronic format that can be
easily accessed and converted to a PDF file. As discussed above, each
NDA applicant submits approximately 9.45 annual reports, each ANDA
applicant submits approximately 16.18 annual reports, and each BLA
applicant submits approximately 1 annual report each year. Therefore,
approximately 66 NDA applicants, 55 ANDA applicants, and 18 BLA
applicants can easily access labeling in electronic form and convert it
to a PDF file. For the applicants submitting these annual reports, the
hours per response, i.e., the additional time necessary for submission
of the content of labeling in electronic format in the annual report,
will be less than 15 minutes. Therefore, respondents would spend
approximately 383 hours per year submitting the content of labeling in
these annual reports under the final rule.

As mentioned previously, a new category has been added to the paperwork
section to allow for proofreading the converted file of labeling that
was previously submitted in annual reports in paper form (and not
requiring any changes since it was last submitted), but is also
maintained by the applicant in an electronic format. For applicants to
include labeling content in their annual reports in electronic format,
approximately 36 percent of NDA annual reports (936 NDA annual reports),
30 percent of ANDA annual reports (1,335 ANDA annual reports), and 36
percent of BLA annual reports (27 BLA annual reports) will be submitted
by applicants who previously submitted labeling in paper, but have such
labeling available in electronic format. As discussed above, each NDA
applicant submits approximately 9.45 annual reports, each ANDA applicant
submits approximately 16.18 annual reports, and each BLA applicant
submits approximately 1 annual report each year. Therefore, under the
final rule, approximately 99 NDA applicants, 83 ANDA applicants, and 27
BLA applicants would need additional time to proofread these annual
reports. The hours per response, i.e., the time it will take an
applicant to submit the labeling content electronically for these annual
reports, will be approximately 5 hours. Therefore, respondents would
spend approximately 11,490 hours per year submitting the content of
labeling in these annual reports under the final rule.

Annual reports for some drug and biological products, particularly older
products for which labeling changes have not been made in several years,
may require additional steps. For applicants to include labeling content
in their annual reports in electronic format, approximately 40 percent
of NDA annual reports (1,040 NDA annual reports), 50 percent of ANDA
annual reports (2,225 ANDA annual reports), and 40 percent of BLA annual
reports (30 BLA annual reports) will be submitted by applicants who may
need to access the labeling in their archives, put the content of
labeling into an electronic format, and convert it to a PDF file. As
discussed above, each NDA applicant submits approximately 9.45 annual
reports, each ANDA applicant submits approximately 16.18 annual reports,
and each BLA applicant submits approximately 1 annual report each year.
Therefore, under the final rule, approximately 110 NDA applicants, 137
ANDA applicants, and 30 BLA applicants would need to put labeling
content in an electronic format and convert it to a PDF file. The hours
per response, i.e., the time it will take an applicant to submit the
labeling content electronically for these annual reports, will be
approximately 10 hours.[^2] Therefore, respondents would spend
approximately 32,950 hours per year submitting the content of labeling
to us in these annual reports under the final rule.

In the first year, respondents will spend approximately 44,823 hours
submitting the content of labeling in annual reports under the final
rule. This expenditure of time will only be necessary the first time
that an annual report is submitted with the content of labeling in
electronic format. Once the content of labeling has been converted to an
electronic format, the time necessary to submit the content of labeling
in subsequent annual reports will be the same as that for the other
types of submissions, or less than 15 minutes. Therefore, in subsequent
years, respondents will spend approximately 1,781 hours per year
submitting the content of labeling in annual reports.

[Description of Respondents]{.underline}: An applicant submitting an
NDA, ANDA, BLA, supplement, or annual report for a drug or biological
product.

Table 1.\--Estimated Annual Reporting Burden[^3]

+---------------+-----------+------------+---------+--------+--------+
| 21 CFR        | Number of | Number of  | Total   | Hours  | Total  |
| Section       |           | Responses  |         | per    | Hours  |
|               | Re        | per        | Re      |        |        |
|               | spondents | Respondent | sponses | Re     |        |
|               |           |            |         | sponse |        |
+---------------+-----------+------------+---------+--------+--------+
| [             | 83        | 1.02       | 85      | .25    | 21     |
| Applications] |           |            |         |        |        |
| {.underline}: |           |            |         |        |        |
|               |           |            |         |        |        |
| 314.50        |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.94        | 117       | 2.76       | 323     | .25    | 81     |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 17        | 1          | 17      | .25    | 4      |
| (Applications |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| § 601.2)      |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Subtotal,     |           |            |         |        | 106    |
| applications  |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| [Supplements] | 167       | 1.52       | 254     | .25    | 63     |
| {.underline}: |           |            |         |        |        |
|               |           |            |         |        |        |
| 314.70        |           |            |         |        |        |
| (Products not |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.70        | 251       | 1.50       | 376     | 5      | 1,880  |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.97        | 61        | 6.50       | 396     | .25    | 99     |
| (Products not |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.97        | 91        | 6.50       | 604     | 5      | 3,020  |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 8         | 1.25       | 10      | .25    | 3      |
| (Supplements  |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| §             |           |            |         |        |        |
|  601.12(f)(1) |           |            |         |        |        |
| and (f)(2))   |           |            |         |        |        |
| (Products not |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 12        | .83        | 10      | 5      | 50     |
|               |           |            |         |        |        |
| (Supplements  |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| §             |           |            |         |        |        |
|  601.12(f)(1) |           |            |         |        |        |
| and (f)(2))   |           |            |         |        |        |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Subtotal,     |           |            |         |        | 5115   |
| supplements,  |           |            |         |        |        |
| year one      |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Subtotal      |           |            |         |        | 413    |
| supplements,  |           |            |         |        |        |
| subsequent    |           |            |         |        |        |
| years[^4]     |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| [Annual       | 66        | 9.45       | 624     | .25    | 156    |
| Reports]      |           |            |         |        |        |
| {.underline}: |           |            |         |        |        |
|               |           |            |         |        |        |
| 314.81        |           |            |         |        |        |
| (Products not |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.81        | 99        | 9.45       | 936     | 5      | 4680   |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.81        | 110       | 9.45       | 1,040   | 10     | 10,400 |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.98        | 55        | 16.18      | 890     | .25    | 222    |
| (Products not |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.98        | 83        | 16.18      | 1,335   | 5      | 6,675  |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 314.98        | 137       | 16.18      | 2,225   | 10     | 22,250 |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission    |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 18        | 1          | 18      | .25    | 5      |
| (Annual       |           |            |         |        |        |
| reports       |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| §             |           |            |         |        |        |
|  601.12(f)(3) |           |            |         |        |        |
| not requiring |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 27        | 1          | 27      | 5      | 135    |
|               |           |            |         |        |        |
| Annual        |           |            |         |        |        |
| reports       |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| §             |           |            |         |        |        |
|  601.12(f)(3) |           |            |         |        |        |
|               |           |            |         |        |        |
| (Products     |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| proofreading) |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| 601.14        | 30        | 1          | 30      | 10     | 300    |
| (Annual       |           |            |         |        |        |
| reports       |           |            |         |        |        |
| submitted     |           |            |         |        |        |
| under         |           |            |         |        |        |
| §             |           |            |         |        |        |
|  601.12(f)(3) |           |            |         |        |        |
| requiring     |           |            |         |        |        |
| additional    |           |            |         |        |        |
| steps for     |           |            |         |        |        |
| electronic    |           |            |         |        |        |
| submission)   |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Subtotal,     |           |            |         |        | 44,823 |
| annual        |           |            |         |        |        |
| reports, year |           |            |         |        |        |
| one           |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Subtotal,     |           |            |         |        | 1,781  |
| annual        |           |            |         |        |        |
| reports,      |           |            |         |        |        |
| subsequent    |           |            |         |        |        |
| years[^5]     |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Total, year   |           |            |         |        | 50,044 |
| one           |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+
| Total,        |           |            |         |        | 2,300  |
| subsequent    |           |            |         |        |        |
| years^2^      |           |            |         |        |        |
+---------------+-----------+------------+---------+--------+--------+

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

FDA has estimated an average industry wage rate of \$50.00 per hour for
preparing and submitting the information collection requirements under
OMB Control Number 0910-0001. Using the averaged wage rate of \$50.00
per hour, and multiplied times the total hour burden estimated above,
the total cost burden to respondents is \$2,617,200 (52,344 x \$50).

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

There will be no new (increased) Federal burden resulting from the final
rule. FDA currently uses the package insert, submitted in paper, to
review both the content and format of the labeling. As a result of the
final rule, FDA will use the content of labeling, submitted
electronically, to review the labeling content and the package insert,
submitted in paper or electronically, to review the labeling format

15\. [Changes In Burden]{.underline}

The changes in burden from the proposed rule are the result of
proofreading estimates and more current estimates for current
submissions.

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

There are no publications.

17\. [Displaying of OMB Expiration Date]{.underline}

The agency is not seeking to display the expiration date for OMB
approval of the information collection.

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

There are no exceptions to the certification statement

identified in Item 19, \"Certification for Paperwork Reduction Act
Submission,\" of OMB Form 83-I.

[^1]: The numbers in the final rule have changed from the proposed rule
    because the numbers have been updated to be more current.

[^2]: The number increased from 8 hours to 10 hours to allow for
    additional time to proofread.

[^3]: There are one-time capital costs to: (1) Acquire computer
    software; (2) train employees to use the software; and (3) convert
    certain labeling to an electronic format. These costs are estimated
    to be about \$2.3 million (see section VIII of this document). There
    are no operating or maintenance costs associated with this
    collection of information.

[^4]: For certain supplements, respondents will spend either 5 hours per
    response in the first year. In subsequent years respondents will
    spend less than 15 minutes per response for all supplements.

[^5]: For certain annual reports, respondents will spend either 5 or 10
    hours per response in the first year. In subsequent years
    respondents will spend less than 15 minutes per response for all
    annual reports.