OMB INFORMATION COLLECTION

SUPPORTING STATEMENT

0910-0527

Certain Biologics Labeling

# JUSTIFICATION

1\. [Circumstances Which Make This Information Collection
Necessary]{.underline}

The Food and Drug Administration (FDA) is requesting Office of
Management and Budget (OMB) approval of the information collection
requirements for the regulations listed below (Tab A):

  ------------------------------------------------ ----------------------
  21 CFR 640.70(a)/ 640.74(b)(3) and (4)           Reporting

  21 CFR 640.84(a) and (c)                         Reporting

  21 CFR 640.94(a)                                 Reporting

  21 CFR 660.2(c)                                  Reporting

  21 CFR 660.28(a) and (b)                         Reporting

  21 CFR 660.35(a)(c-g)(i-m)                       Reporting

  21 CFR 660.45                                    Reporting

  21 CFR 660.55(a) and (b)                         Reporting
  ------------------------------------------------ ----------------------

Under the authority of section 351 of the Public Health Services Act
(PHS Act, 42 U.S.C. 262, Tab B), the biologics regulations require a
manufacturer of a biological product to submit an application with
accompanying information, including labeling information, to FDA for
approval to market a product in interstate commerce (21 CFR 601.2). In
addition, any changes to labeling are required to be submitted to FDA
for review and approval (21 CFR 601.12). For biological products,
excluding blood and blood components for transfusion, the container and
package labeling requirements subject to the Paperwork Reduction Act of
1995 are provided in 21 CFR 610.60, 610.61, and 610.62. The collections
of information under §§ 601.2, 601.12, 610.60, 610.61, and 610.62 are
approved under OMB Control No. 0910-0338 (expires August 31, 2005).

In addition to the labeling requirements prescribed in §§ 610.60 through
610.62 or other labeling regulations (e.g., § 809.10), there are
additional container and/or package labeling requirements for certain
licensed biological products subject to the PRA: §§ 640.70 and 640.74
(Source Plasma), § 640.84 (Albumin), § 640.94 (Plasma Protein Fraction),
§ 660.2 (Antibody to Hepatitis B Surface Antigen), § 660.28 (Blood
Grouping Reagent), § 660.35 (Reagent Red Blood Cells), § 660.45
(Hepatitis B Surface Antigen), and 660.55 (Anti-Human Globulin).

An example of an additional labeling requirement for each of the
specific regulations is as follows:

> Section 640.70(a), the total volume or weight of plasma.

-   Section 640.74(b)(3) and (4), the name of the manufacturer of the
    final blood derivative product for whom it was prepared.

-   Sections 640.84(a) and (c), and 640.94(a), the osmotic equivalent.

-   Section 660.2(c), the name of the recommended test method(s).

-   Section 660.28(a) and (b), the name of the antibody or antibodies
    present.

-   Section 660.35(a)(c-g)(i-m), information regarding washing of cells,
    percentage of red blood cells in suspension.

-   Section 660.45, the name of the recommended test method(s).

-   Section 660.55(a) and (b), the name of the antibody or antibodies
    present.

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. Labeling information is submitted to FDA
for review in an application, supplement, or, when appropriate, an
annual report. Form FDA 2567 is approved under OMB Control No.
0910-0338.

2\. [How, By Whom, and the Purpose for Collecting this
Information]{.underline}

FDA has the responsibility to ensure the safety, purity, potency, and
effectiveness of biological products. The PHS Act and FDA regulations
require manufacturers to submit a license application, including
labeling information, for review and approval prior to marketing a
biological product in interstate commerce. Manufacturers are also
required to submit labeling changes to an approved application. The
information submitted to FDA in a biologics license application (BLA) or
supplement to an approved application is used to determine if a product
is safe, effective, and not misbranded under prescribed, recommended, or
suggested conditions of use. Without this and other information, FDA
could not monitor industry procedures and discharge its statutory
responsibility for protecting the nation's health.

3\. [Use of Information Technology to Reduce the Burden on the
Public]{.underline}

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, FDA\'s Center for Biologics Evaluation and Research 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.

4\. [Identification and Use of Duplicate Information]{.underline}

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

5\. [FDA\'s Efforts to Reduce burden on Small Businesses]{.underline}

FDA believes that its duty requires the equal application of the
regulations to all enterprises. While FDA does not believe it can apply
different standards with respect to statutory requirements, FDA does
provide special help to small businesses. The CBER\'s Office of
Communications, Training, and Manufacturers Assistance provides
assistance to small businesses subject to FDA's regulatory requirements.

6\. [Impact of Not Collecting This Information or Collecting Information
Less Frequently]{.underline}

Manufacturers are required to submit applications with labeling
information 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 necessary information needed by FDA to properly evaluate the
safety, purity, potency, and effectiveness of a biological product.

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

7\. [Special Circumstances That Occur When Collecting This
Information]{.underline}

An applicant may be required to submit to FDA proprietary trade secret
or other confidential information when submitting a license application,
or change to an approved application. 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.

8\. [Identification of Outside FDA Sources]{.underline}

In accordance with 5 CFR 1320.8(d), FDA published a notice in the
Federal Register of July 22, 2003 (68 FR 43359, Tab C) providing for a
60-day comment period on the information collection. We received no
comments on the proposed information collection.

9\. [Payment or Gifts Offered to Respondents]{.underline}

No payment or gift was provided to respondents.

10\. [Method of Ensuring Respondent Confidentiality]{.underline}

The confidentiality of information received by FDA would be consistent
with the Freedom of Information Act and the agency's regulations under
21 CFR Part 20 and 21 CFR 601.51. Manufacturers submitting an
application for FDA approval to market a biological product in
interstate commerce, or any changes to an approved application, may be
required to include proprietary or trade secret information in a license
application submitted for FDA approval. However, such proprietary or
trade secret information is deleted from any information released by FDA
under the Freedom of Information Act and FDA regulations.

11\. [Use of Sensitive Questions]{.underline}

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

12\. [Burden Hours and Cost Associated With This Information
Collection]{.underline}

The total estimated burden for the reporting burdens is 1,061 hours.

+---------------+--------+--------+--------+---------+-------+-----+
| Estimated     |        |        |        |         |       |     |
| Annual        |        |        |        |         |       |     |
| Reporting     |        |        |        |         |       |     |
| Burden        |        |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 21 CFR        | Type   | No. of | Annual | Total   | Hours | To  |
| Section       | of     | Respo  | Fre    | Annual  | per   | tal |
|               |        | ndents | quency | Re      | Res   | Ho  |
|               | Subm   |        | per    | sponses | ponse | urs |
|               | ission |        | Re     |         |       |     |
|               |        |        | sponse |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 640.70(a)/    | appli  | 5      | 1      | 5       | 2     | 10  |
|               | cation |        |        |         |       |     |
| 640.74(b)(3)  |        |        |        |         |       |     |
| and (4)       |        |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 20     | 1.5    | 30      | 25    | 750 |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 640.84(a) and | appli  | 1      | 1      | 1       | 1     | 1   |
| (c)           | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 3      | 1.25   | 4       | 25    | 100 |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 640.94(a)     | appli  | 1      | 1      | 1       | 1     | 1   |
|               | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 1      | 1       | 25    | 25  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 660.2(c)      | appli  | 1      | 1      | 1       | 3     | 3   |
|               | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 1      | 1       | 25    | 25  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 660.28(a) and | appli  | 1      | 1      | 1       | 6     | 6   |
| (b)           | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 2      | 2       | 25    | 50  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 660.35        | appli  | 1      | 1      | 1       | 6     | 6   |
| (a)(c-g)(i-m) | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 1      | 1       | 25    | 25  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 660.45        | appli  | 1      | 1      | 1       | 3     | 3   |
|               | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 1      | 1       | 25    | 25  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| 660.55(a) and | appli  | 1      | 1      | 1       | 6     | 6   |
| (b)           | cation |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
|               | supp   | 1      | 1      | 1       | 25    | 25  |
|               | lement |        |        |         |       |     |
+---------------+--------+--------+--------+---------+-------+-----+
| Total         |        |        |        |         |       | 1,  |
|               |        |        |        |         |       | 061 |
+---------------+--------+--------+--------+---------+-------+-----+

Based on information obtained from CBER's database system, there is an
estimated 350 manufacturers of licensed biological products. 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 for a particular product (e.g.,
license applications, labeling supplements) received annually by FDA. No
applications have been received for most of the listed products in the
last couple of years, however, FDA is using the estimate of one
application in the event one is submitted in the future. Based on
previous estimates, the rate of submissions is not expected to change
significantly in the next few years.

The hours per response is based on past FDA experience with the various
submissions to FDA, and includes the time estimated to prepare the
various submissions for FDA review and collate the documentation. The
burden associated with the additional labeling requirements for
submission in a license application is minimal because the majority of
the burden is associated with the requirements under §§ 610.60 through
610.62 or other labeling requirements. FDA estimates that it takes
between 10 to 40 hours (average 25 hours) to complete a labeling
supplement or annual report for submission to FDA.

[Cost to Respondents]{.underline}

The estimated annual cost to respondents is \$40,318.00.

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

  Reporting         1, 061            \$38.00           \$40,318.00
  ----------------- ----------------- ----------------- -----------------

The cost estimate is based on a regulatory affairs specialist, at a pay
rate of \$38.00/hour, who would be responsible for filling out the form,
and preparing an application, supplement, or other similar submission
with the labeling information. The estimated cost includes benefits but
no overhead costs.

13\. [Annual Cost Estimate to Respondents]{.underline}

There are no capital and start-up, and operation, maintenance and
purchase costs associated with the information collection.

14\. [Annual Cost Estimate to FDA]{.underline}

The estimated annual cost to the Federal Government is \$18,839,711.00.
This estimate is based on the number of full-time equivalents (FTEs)
associated with the review of license applications including
supplemental applications or other similar submissions. The amount of
time and expense incurred by the Federal Government is due to the review
of all material, including labeling information, submitted with an
application, supplement, or other similar submission. This information
is essential to determine the safety and effectiveness of products in
support of FDA's mission to protect the public health. The average
annual salary and benefits for CBER reviewers is \$99,418.00.

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

  Application/Supplement   189.5         \$99,418.00           \$18,839,711.00
  Review                                                       
  ------------------------ ------------- --------------------- -----------------

15\. [Changes From Previous Approval]{.underline}

Changes from the previous approval are not applicable since this is the
first submission for this information collection package.

16\. [Publishing the Results of This Information Collection]{.underline}

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

17\. [Reason for Not Displaying the OMB Approval Date]{.underline}

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

18\. [Explanations to Section 19, \"Certification for Paperwork
Reduction Act Submissions\"]{.underline}

There are no exceptions to Item 19 of OMB Form 83-I.