OMB INFORMATION COLLECTION

SUPPORTING STATEMENT

Revision to the General Safety Requirements for Biological Products

OMB Control Number 0910-0504

[JUSTIFICATION]{.underline}

1\. **[Circumstances Which Make this Collection of Information
Necessary]{.underline}**

The Food and Drug Administration (FDA) is requesting OMB approval of the
information collection requirement contained in the final rule for the
general safety test (GST) requirements (21 CFR 610.11(g)(2) (Tab A). The
information collection for which approval is requested is as follows:

  ----------------- ----------- -------------------------------------------
  21 CFR            Reporting   A manufacturer of certain biological
  610.11(g)(2)                  products may request an exemption from the
                                general safety test requirements contained
                                in 21 CFR 610.11.

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

FDA is revising the requirements for GST set forth in 21 CFR 610.11. The
test may detect harmful contaminants that may enter or be introduced
through undetected failures in the manufacture of biological products.
The revision would add an administrative procedure for obtaining
exemptions from the GST requirements for biological products not already
excepted under  610.11(g)(1). FDA is codifying the new administrative
procedure because alternatives to the GST may be feasible or appropriate
for some biological products. FDA anticipates that manufacturers
requesting exemptions would have demonstrated a record of GST
compliance, well-documented in-process safety controls, and use
sophisticated analytical techniques to adequately characterize the
product and validate its safety. Manufacturers would submit their
requests and documentation to the Director, Center for Biologics
Evaluation and Research (CBER), who may grant the exemption if it is
determined that the manufacturers submission justifies such an action.

FDA is revising the GST as part of FDAs continuing effort to reduce the
burden of unnecessary regulation of biological products without
diminishing the protection of the public health. The final rule adds a
procedure for obtaining an exemption for a biological product. The
agency will continue to use the same criteria to evaluate the safety and
effectiveness of biological products, as well as those receiving an
exemption, that it uses under the authority of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 355) (Tab B) and section 351 of the Public
Health Service Act (42 U.S.C. 262) (Tab C).

In the Federal Register of April 20, 1998, FDA published a direct final
rule and a companion proposed rule to revise the general safety
requirements for biological products (63 FR 19399 and 63 FR 19431,
respectively) (Tab D). The direct final rule amended the regulations to
exempt cellular therapy products from the GST requirement and added an
administrative procedure for manufacturers of other biological products
to request exemptions from performing the GST. FDA published a companion
proposed rule to provide a procedural framework within which the rule
could be finalized in the event FDA received any significant adverse
comments regarding the direct final rule and FDA withdrew or severed the
direct final rule. FDA did not receive any significant adverse comments
to the amendment to specifically exempt cellular therapy products in
21 CFR 610.11(g)(1). FDA received significant adverse comments on the
administrative procedure provision of 21 CFR 610.11(g)(2).

Accordingly, FDA published a notice on August 5, 1998, in the Federal
Register (63 FR 41718, Tab D) confirming in part and withdrawing in part
the direct final rule amending the GST requirements. FDA confirmed a
revision to  610.11(g)(1) to add cellular therapy products to the
list of products excepted from the GST. Based on receipt of adverse
comments, FDA withdrew the revision of  610.11(g)(2) that provided a
general administrative procedure for requesting and obtaining exemptions
from the GST. FDA applied the comments regarding the withdrawn portion
of the rule to the companion proposed rule and considered them in
developing the final rule.

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

The Director, CBER, would use the information to make a proper
determination of whether a particular biological product should be
exempted from the GST. FDA anticipates that the information used to
apply for an exemption would be that which is normally gathered and
organized by manufacturers as part of their compliance with the GST
testing requirements.

3\. **[Use of Information Technology to Reduce 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 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.

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

FDA is the only agency that requires the filing of a request to exempt a
licensed biological product from the requirements of the GST. No other
component of the agency or other government agencies requires similar
information or data to be filed. 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. 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}**

A manufacturer may request an exemption from the GST and only needs to
submit the necessary information when requesting an exemption. There are
no technical 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 secrets
or other confidential information when submitting a license application
or supplement. FDA has instituted security measures to protect
confidential information received from manufacturers and will, to the
extent permitted by law, protect this information.

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

The direct final rule and companion proposed rule of April 20, 1998 (60
FR 19399 and 63 FR 19431, respectively) provided a 60-day public comment
period on the information collection provisions reflected in this final
rule. Although some comments objected to the license supplement
mechanism of gaining approval for an exemption as being too burdensome,
FDA received no comments on the actual burden estimates for submitting
such supplements.

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. However, manufacturers applying to FDA
for exemptions to the GST would not be required to reveal any
proprietary information or trade secrets to obtain the exemption.

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 estimated annual burden for this information collection is 400
hours.

Estimated Annual Reporting Burden

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

  610.11(g)(2)   10            1           10            40           400
  -------------- ------------- ----------- ------------- ------------ -----------

The final rule requires only those manufacturers of biological products
requesting an exemption from the GST under  610.11(g)(2) to submit
additional information as part of a license application or supplement to
an approved license application. Based on our experience, FDA estimates
that it will receive approximately 10 requests for administrative
exemption from the GST under 21 CFR 610.11(g)(2) annually. FDA estimates
that an applicant will take approximately 40 hours to complete and
submit the appropriate information for the exemption request. Since the
applicant ordinarily complies and organizes the information while
performing the GST, FDA anticipates that the additional time needed to
submit an exemption request will be minimal.

[Cost to Respondents]{.underline}

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

  Reporting   400              \$38.00                 \$15,200.00
  ----------- ---------------- ----------------------- --------------------

The cost of submitting the information needed to request an
administrative exemption from the GST would be minimal because that
information is ordinarily compiled and organized by a manufacturer as
part of the production and to remain in compliance with the GST
requirements. The cost estimate is based on a regulatory affairs
specialist, at a pay rate of \$38.00/hour, who would gather, organize,
and submit the required information for the exemption request. The
salary estimates include 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 to FDA]{.underline}**

The estimated annualized cost to the Federal Government is \$18,839,711.
This estimate is based on full-time equivalents (FTEs) associated with
the review of biologics license applications including supplemental
applications. The amount of time and expense incurred by the Federal
government is due to the review of all material submitted with an
application, supplement. 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, and patient information. The
average annual salary and benefits for CBER reviewers is \$99,418.00.

No increase is anticipated because after an exemption request is
approved, FDA reviewers will no longer have to review information that
is no longer required to be submitted by the applicant for the exempted
product.

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

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

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

There is no change in burden as this is the first submission of the
final rule.

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.