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 Which Make This Information Collection
    Necessary.]{.underline}

> The Food and Drug Administration is requesting an extension of Office
> of Management and Budget (OMB) Control No. 0910-0469 and OMB approval
> of the information collection requirements contained in 21 CFR parts
> 207, 807 and 1271 (Tab A) and Form FDA 3356 (Tab B). The information
> requirements are listed below:

+-------------------+---------+---------------------------------------+
| Section 207.20(f) | Re      | Requires that manufacturers of HCT/P  |
|                   | porting | drugs submit this registration and    |
|                   |         | listing information using Form FDA    |
|                   |         | 3356 instead of the multiple forms    |
|                   |         | identified under part 207.            |
+-------------------+---------+---------------------------------------+
| Section 807.20(d) | Re      | Requires that manufacturers of HCT/P  |
|                   | porting | devices submit this registration and  |
|                   |         | listing information using Form FDA    |
|                   |         | 3356 instead of the multiple forms    |
|                   |         | identified under part 807.            |
+-------------------+---------+---------------------------------------+
| Sections          | Re      | Requires the annual establishment     |
|                   | porting | registration by domestic and foreign  |
| 1271.10(b)(1) and |         | HCT/P establishments that are solely  |
| 1271.21(b)        |         | regulated under section 361 of the    |
|                   |         | PHS Act and part 1271.                |
+-------------------+---------+---------------------------------------+
| Sections          | Re      | Requires the initial establishment    |
|                   | porting | registration and HCT/P listing        |
| 1271.10(b)(1) and |         | information.                          |
| (b)(2) and        |         |                                       |
| 1271.25(a) and    |         |                                       |
| (b)               |         |                                       |
+-------------------+---------+---------------------------------------+
| Sections          | Re      | Requires domestic and foreign HCT/P   |
| 1271.10(b)(2),    | porting | establishments to submit HCT/P        |
|                   |         | listing updates only when an HCT/P is |
| 1271.21(c)(2)(ii) |         | changed, added, or discontinued, and  |
| and 1271.25(c)    |         | when there has been a material change |
|                   |         | to information submitted previously   |
|                   |         | to the agency.                        |
+-------------------+---------+---------------------------------------+
| Section 1271.26   | Re      | Requires domestic and foreign HCT/P   |
|                   | porting | establishments to submit an amendment |
|                   |         | when 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) pose some risk of carrying
> pathogens that could infect recipients or handlers. The regulations in
> part 1271 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 can identify industry establishments and
> the HCT/Ps produced. This information assists FDA in reacting in a
> timely manner to emerging or understood risks by alerting members of
> the industry to FDA concerns, and allows FDA to regulate these
> products by performing inspections of the various establishments.
>
> In the Federal Register of January 19, 2001 (66 FR 5447, Tab D), FDA
> published a final rule to require HCT/Ps establishments to register
> with the agency and list their HCT/Ps. This regulation became
> effective April 4, 2001, except for 21 CFR 207.20(f), 807.20(d) and
> 1271.3(d)(2), which were to be effective on January 21, 2003. In the
> Federal Register of January 21, 2003 (68 CFR 2689) (Tab E), FDA
> delayed the implementation date for these three sections from January
> 21, 2003, to a new effective date of January 21, 2004. In the Federal
> Register of January 27, 2004 (69 FR 3823) (Tab F), FDA published an
> interim final rule exempting human dura mater and human heart valve
> allografts from the definition of HCT/Ps subject to the registration
> and listing requirements contained in 21 CFR part 1271. Therefore, at
> present all establishments that engage in the recovery, screening,
> testing, processing, storage, or distribution of all HCT/Ps except for
> dura matter and heart valve allografts are subject to the registration
> and listing requirements for HCT/Ps.

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

> The information that FDA will receive when establishments of HCT/Ps
> comply with the registration and listing requirements will give FDA
> the information necessary to regulate the industries involved with the
> recovery, screening, testing, processing, storage, and distribution of
> HCT/Ps. The information will allow FDA to efficiently and effectively
> handle emerging public health concerns related to HCT/Ps. The
> information will also aid FDA to monitor the industry, to distribute
> educational materials, and to inform the industry about FDA
> requirements, guidances, and policies, and to identify entities that
> may be subject to FDA regulation.
>
> The regulations for the establishment registration and listing of
> HCT/Ps which became effective on January 21, 2004, establishes the
> foundation for a regulatory program that will prevent the transmission
> of communicable diseases. Additional regulations dealing with issues
> such as donor suitability and good tissue practices, will be
> incorporated into this regulatory program. Without the information
> collected through establishment registration and product listing, FDA
> could not effectively prevent the transmission of communicable disease
> or monitor compliance with future regulations concerning HCT/Ps.

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

> To facilitate establishment registration and listing, FDA has
> developed Form FDA 3356 that may be submitted electronically through a
> secure web server, or in paper form by mail or FAX. FDA is not aware
> of any other improved technology to reduce the burden.

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

> Manufacturers of drug or device products that incorporate human cells
> or tissues register only using Form FDA 3356. This avoids duplicate
> registration and listing under both 21 CFR parts 207 or 807, and 1271.

5.  [FDA's Efforts to Reduce Burden on Small Business.]{.underline}

> Although FDA must apply the statutory and regulatory requirements
> equally to all enterprises, FDA does provide special help to small
> businesses. FDA's Center for Biologics Evaluation and Research, Office
> of Communications, Training, and Manufacturer's 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}

> Less frequent collection of information would not provide FDA 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 That Occur When Collecting this
    Information.]{.underline}

> There are no special circumstances for the information collection
> requirements.
>
> 8\. [Identification of Outside FDA Sources.]{.underline}
>
> In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice
> requesting public comments on the information collection provisions in
> the Federal Register on January 29, 2004 (69 FR 4303 (Tab G)). No
> comments were received from the public.

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

> No payment or gift was provided to respondents.

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

> The confidentiality of the information received by FDA is consistent
> with the Freedom of Information Act and the agency's regulations under
> 21 CFR Part 20. Establishments registering and listing their HCT/P
> products with FDA are not required to reveal any proprietary
> information or trade secrets to be in compliance with the HCT/P
> registration and listing requirements.
>
> 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 1,005
> hours.

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

+-------------+---------+--------+---------+---------+-------+-------+
| 21 CFR      | Form    | No. of | Annual  | Total   | Hours | Total |
| Section     | FDA     | Respo  | Fr      | Annual  | per   | Hours |
|             | 3356    | ndents | equency | Re      | Res   |       |
|             |         |        | per     | sponses | ponse |       |
|             |         |        | R       |         |       |       |
|             |         |        | esponse |         |       |       |
+-------------+---------+--------+---------+---------+-------+-------+
| 207.20(f)   | Change  | 1      | 1       | 1       | 0.5   | 0.5   |
|             | to      |        |         |         |       |       |
| 807.20(d)   |         | 66     | 1       | 66      | 0.5   | 33    |
|             | Form    |        |         |         |       |       |
| 12          | 3356    | 300    | 1       | 300     | 0.75  | 225   |
| 71.10(b)(1) |         |        |         |         |       |       |
| and (2),    | Initial |        |         |         |       | 258.5 |
| 1271.21(a), | Regis   |        |         |         |       |       |
| and         | tration |        |         |         |       |       |
|             | And     |        |         |         |       |       |
| 1271.25(a)  | Listing |        |         |         |       |       |
| and (b)     |         |        |         |         |       |       |
|             |         |        |         |         |       |       |
| Total       |         |        |         |         |       |       |
+-------------+---------+--------+---------+---------+-------+-------+

Table 2. - Estimated Annual Reporting Burden

+-------------+---------+--------+----------+---------+-------+------+
| 21 CFR      | Form    | Number | Annual   | Total   | Hours | T    |
| Section     | FDA     | of     | F        | Annual  | per   | otal |
|             | 3356    | Respo  | requency | Re      | Res   | H    |
|             |         | ndents | per      | sponses | ponse | ours |
|             |         |        | Response |         |       |      |
+-------------+---------+--------+----------+---------+-------+------+
| 12          | Annual  | 1,003  | 1        | 1,003   | 0.5   | 5    |
| 71.10(b)(1) | Regis   |        |          |         |       | 01.5 |
| and         | tration | 484    | 1        | 484     | 0.5   |      |
| 1271.21(b)  |         |        |          |         |       | 242  |
|             | Listing | 12     | 1        | 12      | 0.25  |      |
| 127         | Update  |        |          |         |       | 3    |
| 1.10(b)(2), |         |        |          |         |       |      |
| 1271        | Regis   |        |          |         |       | 7    |
| .21(c)(ii), | tration |        |          |         |       | 46.5 |
| and         | Am      |        |          |         |       |      |
| 1271.25(c)  | endment |        |          |         |       |      |
|             |         |        |          |         |       |      |
| 1271.26     |         |        |          |         |       |      |
|             |         |        |          |         |       |      |
| Total       |         |        |          |         |       |      |
+-------------+---------+--------+----------+---------+-------+------+

Respondents to this information collection are establishments that
recover, process, store, label, package, or distribute any HCT/P, or
perform donor screening or testing. In table 2, based on information
from FDA's database system for the fiscal year (FY) 2003 there are 1,003
establishments that have registered and listed with FDA. This number
includes 552 establishments manufacturing conventional or ocular HCT/Ps,
which are currently required to register and list with FDA. The
remaining 451 establishments are manufacturers of hematopoietic stem
cells derived from peripheral or cord blood, and reproductive cells and
tissue. Although these establishments were not required to register and
list, some have registered voluntarily and are therefore included in the
burden estimate. Based on information from FDA's database for FY 2002,
there were 484 listing updates and 12 location/ownership amendments.
When registration and listing requirements for all HCT/P establishments,
except for those HCT/P products involving human dura matter and human
heart valve allografts became effective on January 21, 2004, FDA
estimates in table 1 that approximately 367 (300+66+1) HCT/P
establishments would initially register and list in addition to the
1,003 currently registered establishments.

The burden estimates for the initial registration and listing 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, a
consulting firm hired by FDA to prepare an economic analysis of the
potential economic impact on sperm banks and other reproductive tissue
facilities.

> [Cost to Respondents]{.underline}

+-----------------+-----------------+----------------+-----------------+
| Activity        | Number of Hours | Cost per hour  | Total Cost      |
+-----------------+-----------------+----------------+-----------------+
| Reporting       | 258.5           | \$42           | \$10,857        |
|                 |                 |                |                 |
| (one-time       |                 |                |                 |
| burden)         |                 |                |                 |
+-----------------+-----------------+----------------+-----------------+
| Reporting       | 746.5           | \$42           | \$31,353        |
|                 |                 |                |                 |
| (annual cost)   |                 |                |                 |
+-----------------+-----------------+----------------+-----------------+
| Total           |                 |                | \$42,210        |
+-----------------+-----------------+----------------+-----------------+

> The estimated annual cost to respondents is estimated at \$42,210.
> This estimated cost is based on a pay rate of \$42/hour for a
> supervisor who will be responsible for completing and submitting the
> registration and/or listing information. This salary estimate includes
> benefits but no overhead costs.
>
> 13 [Annual Cost Estimate to Respondents.]{.underline}
>
> There are no capital and start-up, operation, maintenance, or purchase
> costs associated with the information collection requirements.

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

> The estimated annual cost to FDA is \$156,605. This cost is based on 2
> FTEs (GS-13/5 and GS-7/5) that process and review the registration
> form, input the data, and maintain the database. These cost estimates
> include benefits but no overhead costs.

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

  Registration and GS-7/5             \$50,365           \$50,365
  Listing                                                

  Registration and GS-13/5            \$106,240          \$106,240
  Listing                                                

  Total                                                  \$156,605
  ---------------- ------------------ ------------------ ----------------

15. [Changes from Previous Approval.]{.underline}

> The previous burden estimate was 1,525.25 hours. The current overall
> decrease (-520.25) in burden to 1,005 hours is mostly attributed to
> the decrease in the number of establishments required to report for
> initial registration and listing as most existing establishments have
> registered and listed their products. The slight increase under the
> listing update (21 CFR 1271.10(b)(2), 1271.21(c)(ii), 1271.25(c)) is
> attributed to the increase in the number of respondents who have to
> submit product listing updates as required by FDA regulations.

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

> There are no tabulated results to be published 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.