OMB INFORMATION COLLECTION

SUPPORTING STATEMENT

Human Cells, Tissues, and Cellular and Tissue-Based Products;

Establishment Registration and Listing

OMB \# 0910-0469

[JUSTIFICATION]{.underline}

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

The Food and Drug Administration (FDA) is requesting Office of
Management and Budget (OMB) approval of the information collection
requirements contained in 21 CFR Parts 1271, 207 and 807 (Tab A), and
Form FDA 3356 (Tab B). The information collection requirements are
listed below:

  ------------------- ----------- ------------------------------------------
  **Section           Reporting   **Requires that manufacturers of HCT/P
  207.20(f)**                     drugs submit this registration and listing
                                  information using Form FDA 3356 instead of
                                  the multiple forms identified under part
                                  207.**

  **Section           Reporting   **Requires that manufacturers of HCT/P
  807.20(d)**                     devices submit this registration and
                                  listing information using Form FDA 3356
                                  instead of the multiple forms identified
                                  under part 807.**

  **Sections          Reporting   **Require the annual establishment
  1271.10(b) and                  registration by domestic and foreign HCT/P
  1271.21(b)**                    establishments that are solely regulated
                                  under section 361 of the PHS Act and this
                                  part.**

  **Sections          Reporting   **Require the initial establishment
  1271.10(b), and                 registration and HCT/P listing
  1271.25(a) and                  information.**
  (b)**                           

  **Sections          Reporting   **Require domestic and foreign HCT/P
  1271.10(b),                     establishments to submit HCT/P listing
  1271.21(c), and                 updates only when an HCT/P is changed,
  1271.25(c)**                    added, or discontinued, and when there has
                                  been a material change to information
                                  submitted previously to the agency.**

  **Sections          Reporting   **Require domestic and foreign HCT/P
  1271.10(b) and                  establishments to submit an amendment when
  1271.26**                       the establishment makes a change in
                                  location or ownership.**
  ------------------- ----------- ------------------------------------------

Under section 361 of the Public Health Service (PHS) Act (42 U.S.C. 264,
Tab C), FDA may issue and enforce regulations necessary to prevent the
introduction, transmission, or spread of communicable diseases between
the States or from foreign countries into the States. As derivatives of
the human body, all human cells, tissues, and cellular and tissue-based
products (HCT/Ps) poses some risk of carrying pathogens that could
infect recipients or handlers. FDA is taking the first step in the
regulation of the rapidly evolving industry of human cells and tissue by
promulgating this regulation to require all manufacturers of HCT/Ps to
register with the agency and to submit to the agency a list of their
HCT/Ps. Through registration and listing, FDA will be able to identify
industry participants and the scope of the HCT/Ps produced. The
information from the registration rule will assist FDA in reacting
swiftly to newly discovered or understood risks by alerting members of
the industry to FDA concerns and, when appropriate, by conducting
establishment inspections.

In the Federal Register of May 14, 1998 (63 FR 26744, Tab D), FDA
published the proposed rule to promulgate regulations that will require
establishments which manufacture HCT/Ps to register and list their
products with the agency. The information collection package for the
proposed rule was approved by OMB on July 6, 1998 under OMB control
number 0910-0372. **However, a new information collection package will
be submitted to OMB for review for this final rule to reflect the
changes made to the proposed rule.**

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

The information to be submitted in compliance with the registration and
listing requirements will provide baseline data on the human cell and
tissue establishments and information needed to characterize the nature
and extend of their HCT/Ps. This information will enable the agency to
efficiently and effectively respond to emerging public health concerns
related to human cells or tissue. It will also help FDA to monitor the
industry, to disseminate educational materials and other important
information regarding FDA guidances, policies, or requirements, and
identify entities that may be subject to FDA oversight.

The regulation now being finalized forms the foundation for a regulatory
program that will further the goal of preventing the transmission of
communicable diseases. Additional regulations to be promulgated in
forming the regulatory program include measures as donor-suitability,
good tissue practices. Without the information collected through
establishment registration and product listing, FDA could not
effectively prevent the transmission of communicable disease or monitor
compliance with the future regulations.

3\. [Use of Information Technology and Burden Reduction]{.underline}

FDA provides a one page registration and listing form (Form FDA 3356) to
facilitate the ease and speed of submissions. FDA plans to provide for
full electronic submission of establishment registration and HCT/P
listing through the internet. FDA is not aware of any other improved
technology to reduce the burden.

4\. [Efforts to Identify Duplication and Use of Similar
Information]{.underline}

The agency has carefully created the establishment registration and
product listing scheme to avoid unnecessary duplication of information
collection to target only human cellular and tissue-based products that
are not currently regulated by the agency. To avoid duplication of
registration and listing, drug or device products that incorporate human
cells or tissues will register [only]{.underline} using Form FDA 3356.
This will avoid duplicate registration and listing under both 21 CFR 207
or 807, and 1271.

5\. [Impact on Small Businesses or Other Entities]{.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 Center for Biologics
Evaluation and Research, Office of Communications, Training, and
Manufacturers Assistance provides assistance to small businesses subject
to FDA's regulatory requirements.

6\. [Consequences of Collecting the Information Less
Frequently]{.underline}

Less frequent collection of information or other methods of reducing the
frequency of information would not provide the information needed to
prevent the transmission of communicable disease by HCT/Ps through
monitoring and communication with the cell and tissue industry.

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

7\. [Special Circumstances Relating to the Guideline of 5 CFR
1320.5]{.underline}

There is no special circumstance for the collection of the information
requirements.

8\. [Comments in Response to the Federal Register Notice an Efforts to
Consult Outside the Agency]{.underline}

A 60-day notice requesting comments from the public on the information
collection provisions was provided in the proposed rule published in the
Federal Register on May 14, 1998 (63 FR 26744). No comments were
received from the public.

9\. [Explanation of Any Payment or Gift to Respondents]{.underline}

No payment or gift was provided to respondents.

10\. [Assurance of Confidentiality Provided to Respondents]{.underline}

The confidentiality of information received by FDA is consistent with
the Freedom of Information Act and the agency's regulations under 21 CFR
Part 20. Manufacturers registering and listing their products with the
agency would not be required to reveal any proprietary information or
trade secrets to achieve compliance with the final rule.

11\. [Justification for Sensitive Questions]{.underline}

No questions of a sensitive nature would be asked by FDA of the
registering and listing manufacturers.

12\. [Estimate of Hour Burden Including Annualized Hourly
Costs]{.underline}

The estimated annual burden for this information collection is 1525.25
hours.

**Table 1.\--Estimated Initial (One-Time) Reporting Burden**

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

  207.20(f)     1             1                1           0.5        0.5

  807.20(d)     65            1                65          0.5        32.5

  1271.10(b),   1,159         1                1,159       0.75       869.25
  1271.25(a),                                                         
  and                                                                 
  1271.25(b)                                                          

  Total                                                               
  ------------- ------------- ---------------- ----------- ---------- --------

**Table 2.\--Estimated Annual Reporting Burden**

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

  Annual Registration  1,159         1             1,159       0.5        579.5
  1271.10(b) and                                                          
  1271.21(b)                                                              

  HCT/P Listing Update 58            1             58          0.5        29
  1271.10(b),                                                             
  1271.21(c), and                                                         
  1271.25(c)                                                              

  Location/Ownership   58            1             58          0.25       14.5
  Amendment 1271.10(b)                                                    
  and 1271.26                                                             

  Total                                                                   
  -------------------- ------------- ------------- ----------- ---------- --------

**Respondents to this information collection are establishments that
recover, process, store, label, package, or distribute any human cells,
tissue, and cellular and tissue-based product.** **Based on information
provided to FDA by industry representatives, trade organizations, and
professional societies, we have revised our estimate number of
establishments to approximately 1,225 (i.e., approximately 110
conventional tissue, 114 eye tissue banks, 400 peripheral blood stem
cells, 25 stem cell products from cord blood, 400 reproductive tissue,
110 sperm banks, and 66 licensed biological products and approved
devices). Our burden estimates for the annual frequency per response and
average hours per response are based on institutional experience with
comparable reporting provisions for drugs, including biological
products, and devices, information from industry representatives and
trade organizations, and data provided by the Eastern Research Group
(ERG), a consulting firm hired by FDA to prepare an economic analysis of
the potential economic impact on sperm banks and other reproductive
tissue facilities.**

**In the final rule, we have separated the initial, one-time reporting
requirements (Table 1) from the subsequent ongoing annual establishment
registration, HCT/P updates and amendment requirements (Table 2).**

**Table 1 provides the initial, one-time estimated burden for
registration and HCT/P listing submitted on Form FDA 3356 by HCT/P
establishments required to register under 21 CFR 1271. We estimate that
0.75 hour of staff time will be needed for each initial submission. This
estimate is based on a pilot program conducted by FDA to evaluate Form
FDA 3356. In Table 1 we also include the one-time burden for HCT/P drug
and device manufacturers regulated under 21 CFR parts 207 and 807. Parts
207 and 807 require that drug and device manufacturers submit initial
establishment registration and product listing, annual establishment
registration, product listing updates*,* and location/ownership
amendments. New sections 207.20(f) and 807.20(d) change only the
reporting format and require use of only one form*,* new Form FDA
3356*,* in place of the multiple forms currently required, i.e., Forms
FDA 2656 and FDA 2657 for drug manufacturers*,* and Forms FDA 2891, FDA
2891(a), and FDA 2892 for device manufacturers. Therefore, the one-time
reporting burden estimate for §§ 207.20(f) and 807.20(d) in Table 1
reflects only the time necessary for familiarizing themselves with the
new registration system and to modify procedures, computer software,
etc., consistent with the registration system. In the proposed rule, the
time needed to submit the registration and listing information already
required under parts 207 and 807 was incorrectly included.**

**Table 2 shows more accurately than in the proposed rule that on-going
annual registration, updates and amendments require 0.5 hour, while the
initial submission requires on average 0.75 hour. This is because more
time is initially required for the establishments to familiarize with
the required form and procedure, and to gather information in submitting
the form. In addition, Table 2 shows that the average hours per response
is less for the HCT/P listing updates and location/ownership amendments,
which are required only when a change is made, than for the annual
registration, which must be submitted every year. This is a change from
the proposed rule that would require semi-annual update of product
listing during each June and December. In Table 2, it is also estimated
that approximately 5 percent of the 1,159 establishments, or 58
establishments, will make changes to HCT/Ps, location, or ownership in
any one year after the initial registration and listing. Based on
additional information from industry representatives and from our own
experiences, we estimate that annual registration, HCT/P listing
updates, and location/ownership amendments will require 0.5, 0.5, and
0.25 hours, respectively, as opposed to the full hour estimated for
every establishment submission in the proposed rule. The greater
precision afforded by this breakout shows that, despite the increased
number of total estimated respondents, the estimated total burden hours
is lower than in the proposed rule. In Table 2, the total annual burden
of 623 hours for ongoing reporting is slightly less than the initial,
one-time reporting burden total of 902.25 hours in Table 1.**

[Cost to Respondents]{.underline}

+-----------------+-----------------+-----------------+-----------------+
| Activity        | No. of Hours    | Cost per hour   | Total Cost      |
+-----------------+-----------------+-----------------+-----------------+
| Reporting       | 902.25          | \$38            | \$34,285.50     |
|                 |                 |                 |                 |
| (one-time       |                 |                 |                 |
| burden)         |                 |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Reporting       | 623             | \$38            | \$23,674.00     |
|                 |                 |                 |                 |
| (annual cost)   |                 |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Total           |                 |                 |                 |
+-----------------+-----------------+-----------------+-----------------+

The annual cost to the respondents is estimated at \$57,959.50. This
cost is calculated using \$38/hour for a supervisor of an establishment
who will be responsible for completing and submitting the registration
and/or listing information. This salary estimate includes benefits but
no overhead costs.

13\. [Estimate of Other Total Annual Cost Burden to Respondents of
Recordkeepers]{.underline}

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

14\. [Annualized Cost to the Federal Government]{.underline}

There will be costs to the Federal Government to (1) implement the first
phase of the registration program for human tissue currently regulated
under 21 CFR Part 1270; e.g., print and distribute registration and
listing forms and process incoming information, (2) fund scientific
information gathering, analysis, and policy development in the interim
period before the full regulatory program is implemented, and (3)
implement the comprehensive regulatory program for the full scope of
HCT/Ps included in the final rule. For the first phase of the
registration program, FDA estimates that 1 FTE and supporting expenses
will be needed. During the interim period leading up to full
implementation of the new program, FDA estimates that approximately 5
FTEs and \$300,000 will be needed.

15\. [Explanation of Program Changes or Adjustments]{.underline}

Changes in burden is not applicable as this is the first submission for
the final rule.

16\. [Plans for Tabulation and Publication and Program Time
Schedule]{.underline}

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

17\. [Reason(s) Display of Expiration Date is Inappropriate]{.underline}

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

18\. [Exceptions to Certification for Paperwork Reduction Act
Submission]{.underline}

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