0543 SS for 2017 Extension

Food and Drug Administration
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps):
Establishment Registration and Listing; Form FDA 3356;
Eligibility Determination For Donors;
and Current Good Tissue Practice (CGTP)
OMB Control No. 0910-0543
Supporting Statement
A. Justification
1. Circumstances Making the Collection of Information Necessary
The information collection supports agency regulations. Under the Federal Food, Drug, and
Cosmetic Act (the FFDCA) and section 361 of the Public Health Service Act (the PHS Act)(42
U.S.C. 264), the Food and Drug Administration (FDA) has promulgated regulations at 21 CFR
Part 1271 regarding human cells, tissues, and cellular and tissue-based products including
requirements for the registration and listing by manufacturers of these products. The regulations
also establish donor-eligibility as well as Current Good Tissue Practice, and are intended to
prevent the transmission and spread of communicable disease. Accordingly, FDA is requesting
approval of the information collection provisions found in 21 CFR Part 1271 as identified and
discussed below. We are also requesting the approval of associated Form FDA 3356 entitled,
“ESTABLISHMENT REGISTRATION AND LISTING FOR HUMAN CELLS, TISSUES,
AND CELLULAR AND TISSUE-BASED PRODUCTS (HCT/Ps)” Form FDA 3356 has been
revised consistent with current rulemaking (81 FR 60170, approved under OMB Control No.
0910-0829) as follows: (1) Adding import contact information including an email address and
phone number; (2) deleting columns related to HCT/Ps subject to registration and listing under
21 CFR part 207 or 807; and (3) revising the instructions accordingly.
2. Purpose and Use of the Information Collection
The information FDA receives from establishments complying with registration and listing
requirements is necessary to regulate the industries involved with the recovery, screening,
testing, processing, storage, and distribution of HCT/Ps. The information allows FDA to
efficiently and effectively handle emerging public health concerns related to HCT/Ps. The
information also aids 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.
Documentation of donor eligibility determination provides to the user that all of the donor’s
medical history and social behavior were reviewed for high risk for or clinical evidence of
communicable diseases, and that all of the required testing was completed. Each distributed
HCT/P must have the following accompanying documentation: (1) a distinct identification code;
(2) a statement, based on the screening and testing results, that the donor is determined to be
eligible or ineligible; and (3) a summary of the records used to determine eligibility. The
summary of records must contain: (1) a statement that the testing was performed by a Clinical
Laboratory Improvement Amendments certified laboratory or by a laboratory that has met

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equivalent requirements as determined by the Centers for Medicare and Medicaid Services; (2) a
listing and interpretation of the results of all communicable disease tests performed; (3) the name
and address of the establishment determining the eligibility of the donor; and (4) in the case of an
HCT/P from a donor determined to be ineligible based on screening and released for use under §
1271.65(b), a statement noting the reason for the ineligible determination.
Other reporting and recordkeeping requirements in 21 CFR Part 1271 are designed to fully
disclose the screening and testing results to the user when using products from donors who are
determined to be ineligible or whose eligibility has not yet been determined in an urgent medical
need. The distributing establishment is also to document that the HCT/P establishment notified
the physician that the screening and testing are not completed. HCT/P establishments are
required to maintain records for a minimum of 10 years. Certain HCT/Ps have long storage
periods and advances in medical diagnosis and therapy also have created opportunities for
disease prevention or treatment many years after a recipient’s exposure to a donor later
determined to be at risk for communicable disease agents or diseases.
The CGTP information collection provisions provide: (1) additional measures for preventing the
introduction, transmission, or spread of communicable disease; (2) step-by step consistency in
the manufacturing of the product; (3) necessary information to FDA for the purpose of protecting
public health and safety; (4) accountability in the manufacturing of cellular and tissue-based
products; and (5) information facilitating the tracking of a product back to its original source or
to a consignee or final disposition.
Without this collection of information, FDA could not monitor HCT/Ps procedures and could not
fulfill its statutory responsibility to ensure that communicable diseases are not spread into or
throughout the United States and its Possessions.
3. Use of Improved Information Technology and Burden Reduction
FDA has developed Form FDA 3356 which may be submitted electronically through a secure
web server or in paper form by mail or FAX. Establishments may maintain records
electronically or as original paper records, or as true copies such as photocopies, microfiche, or
microfilm. Electronic recordkeeping is specifically referred to in the regulations under §
1271.270(c). Advanced methods of recordkeeping, e.g., by an electronic method, have improved
the ability of HCT/P establishments to more easily maintain and retrieve records of donor
eligibility determinations, and CGTP.
4. Efforts to Identify Duplication and use of Similar Information
Manufacturers of drug or device products that incorporate human cells or tissues register only
using Form FDA 3356. To avoid duplication, 21 CFR Parts 210, 211, and 820 state that in the
event of a conflict between applicable regulations in Parts 210, 211, and 820 and the regulations
in part 1271, the regulation specifically applicable to the product in question must supersede the
more general. We are otherwise unaware of any potential duplicative information collection.

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5. Impact on Small Businesses or Other Small Entities
The regulatory requirements apply to all respondents. To assist small businesses, FDA provides
industry guidance on its website and has established small business assistance contacts
throughout the agency including the Office of Communications, Outreach, and Development,
Division of Manufacturer’s Assistance and Training within FDA’s Center for Biologics
Evaluation and Research (CBER).
6. Consequences of Collecting the Information Less Frequency
Information collection is consistent with statutory requirements. 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. The documentation of donor eligibility, the summary of records, and the
information provided to physicians on the donor’s eligibility when a product is used in an urgent
medical need is the minimum necessary to keep the industry informed of the eligibility of each
and every donor of HCT/Ps. The reporting and recordkeeping requirements of CGTP are
designed to impose minimum burden on industry while preventing the introduction,
transmission, or spread of communicable disease through the use of HCT/Ps. There are no
technical or legal obstacles to reducing the burden.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
The reporting burden under 21 CFR Part 1271, subparts C and D require respondents to provide
information more often than quarterly, i.e., for each individual HCT/P. This information
includes an identification code number, which protects patient/donor confidential information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60 day notice for public comment in the
Federal Register of September 7, 2016 (81 FR 61685). No comments were received. Also, in
the Federal Register of August 31, 2016, FDA finalized its rule entitled, “Requirements for
Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including
Drugs that are Regulated Under a Biologics License Application, and Animal Drugs” revising
the information collection. No comments were received regarding the information collection
provisions.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift was provided to respondents.
10. Assurance of Confidentiality provided to respondents
The confidentiality of information received by FDA would be consistent with the Freedom of
Information Act (FOIA) and FDA’s published regulations of “Public Information” under 21 CFR

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Part 20. Inspectors may copy records as part of the inspection of a tissue establishment. This
information is for internal use and may be subject to, in whole or in part, the FOIA and
applicable FDA regulations.
11. Justification for Sensitive Questions
Questions of a sensitive nature, such as sexual behavior and other matters that are commonly
considered private must be asked by the HCT/P establishments as part of the donor medical
history evaluation. The answers to these questions help determine the eligibility of a donor.
Donors that do not meet certain criteria would be determined ineligible to donate. This
information is necessary to prevent the transmission of relevant communicable diseases and to
protect the public health. Such information may be reviewed by FDA during an inspection.
12. Annualized Burden Estimate
12a. Annualized Burden Estimate
We estimate the burden of the information collection as follows:
Table 1- Estimated Annual Reporting Burden1
21 CFR Section
1271.10(b)(1) and 1271.21(b)2
1271.10(b)(1) and (b)(2),
1271.21(a), and 1271.25(a) and
(b)2
1271.10(b)(2), 1271.21(c)(2)(ii)
and 1271.25(c)2
1271.262
1271.155(a)
1271.350(a)(1) and (a)(3)
1271.420(a)

No. of
Respondents
2,218

No. of
Responses per
Respondent
1

Total
Annual
Responses
2,218

182

1

182

1,221

1

1,221

588

1

588

25

3.12

78

34
200

4.88
2.8

166
560

Avg.
Burden per
Response
.5
(30 mins)
.75
(45 mins)

Total
Hours3

.5
(30 mins)
.25
(15 mins)
3
1
.25
(15 mins)

Total
1

There are no capital costs or operating and maintenance costs associated with this collection of information.
2
Using Form FDA 3356.
3
Rounded to the nearest whole number.

1,109
137

611
147
234
166
140

2,544

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Table 2 – Estimated Annual Recordkeeping Burden1
21 CFR Section

No. of
Recordkeepers

No. of Records
per
Recordkeeper

Total Annual
Records

Avg. Burden
per
Recordkeeping

Total
Hours3

New SOPs2
SOP Update2
1271.47(d)
1271.50(a)
1271.55(d)(1)
1271.55(d)(2)
1271.55(d)(4)
1271.60(d)(3) and (d)(4)
1271.65(b)(3)(iii)
1271.155(f)

182
2,218
1,109
2,218
2,218
2,218
2,218
665

1
1
1
49.15
49.15
1
1
1

182
2,218
1,109
109,019
109,019
2,218
2,218
665

48
24
1
5
1
1
120
2

8,736
53,232
1,109
545,095
109,019
2,218
266,160
1,330

25

3.12

78

20

1271.160(b)(3) and (b)(6)
1271.160(d)
1271.190(d)(2)
1271.195(d)
1271.200(e)
1271.210(d)
1271.230(a)
1271.230(c)
1271.260(d)

1,561
1,561
1,561
1,561
1,561
1,561
1,561
1,561
1,561

12
12
12
12
12
12
12
1
12

18,732
18,732
18,732
18,732
18,732
18,732
18,732
1,561
18,732

1271.260(e)

1,561

365

569,765

1271.265(c)(1)

1,561

1,324.08

2,066,890

1271.265(c)(3)
1271.265(e)

781
1,561

1
1,324.08

781
2,066,890

1271.270(a)

1,561

1,324.08

2,066,890

1271.270(e)

1,774

2

3,548

1271.290(d) and (e)

1,561

66.25

103,419

1271.320(b)
Total

1,249

5

6,245

.25
(15 minutes)
1
1
1
1
1
1
1
1
.25
(15 minutes)
.083
(5 minutes)
.083
(5 minutes)
1
.083
(5 minutes)
.25
(15 minutes)
.5
(30 minutes)
.25
(15 minutes)
1

1

18,732
18,732
18,732
18,732
18,732
18,732
18,732
1,561
4,683
47,291
171,552
781
171,552
516,723
1,774
25,855
6,245
2,066,060

There are no capital costs or operating and maintenance costs associated with this collection of information.
Sections 1271.47(a), 1271.85(b)(2), 1271.160(b)(2) and (d)(1), 1271.180(a), 1271.190(d)(1), 1271.200(b), 1271.200(c),
1271.230(a), 1271.250(a), 1271.265(e), 1271.265(f), 1271.270(b) and (d), 1271.290(b)(1), and 1271.320(a).
3
Rounded to the nearest whole number.
2

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Table 3 – Estimated Annual Third-Party Disclosure Burden1
21 CFR Section

No. of
Respondents

No. of
Disclosures per
Respondent

Total Annual
Disclosures

1271.55(a)

1,551

1,422.88

2,206,890

1271.60(c) and (d)(2)

1,375

416

572,000

1271.290(c)

1,561

1,324.08

2,066,890

1271.290(f)
1271.370(b) and (c)

1,561
1,561

1
1,324.08

1,561
2,066,890

Average
Burden per
Disclosure

.5
(30 minutes)
.5
(30 minutes)
.083
(5 minutes)
1
.25
(15 minutes)

Total
1

Total
Hours

1,103,445
286,000
171,552
1,561
516,723
2,079,281

There are no capital costs or operating and maintenance costs associated with this collection of information.

12b. Annualized Cost Estimate
The estimated annual cost to respondents is $201,274,895.00.
Activity

No. of Hours

Cost per Hour

Total Cost

Reporting

2,544

$55

$139,920

Recordkeeping

2,066,060

$42

$86,774,520

Disclosure

2,079,281

$55

$114,360,455

Total

$201,274,895

The reporting/disclosure cost estimate is based on an average pay rate of $55 an hour. The
average is based on the salaries of a medical director ($80/hour), a mid-level supervisor
($51/hour, responsible for completing and submitting the registration and/or listing information;
creating, reviewing, or updating SOPs; or on other reporting responsibilities), and a medical
technician ($34/hour). The recordkeeping cost estimate is based on an average pay rate of
$42/hour of a mid-level professional and a medical technician who are involved with the
documentation and maintenance of records. The estimated average hourly pay rate includes
benefits but no overhead costs.
13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no capital costs or operating and maintenance costs associated with this collection of
information.

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14. Cost to the Federal Government
The estimated annualized cost to FDA is $3,906,619.00.
Activity
Registration and Listing
Exemption or Alternative
Request
Establishment (non-reproductive)
Inspection
Establishment (reproductive)
Inspection
AER triage/review
Total

Number of
Responses
4,209
78

Hours per
Response
3
3

Cost per
Hour
$43
$69

Total Cost

781

69

$59

$3,179,451

164

17

$59

$164,492

166

1/2 (30 mins)

$43

$3,569
$3,906,619

$542,961
$16,146

The estimated cost is based on 2 FTEs (GS-7/5 and GS-13/5) who process and review the
registration form, input the data, and maintain the database; and who triage and review AERs.
There are approximately 1,561 non-reproductive HCT/P establishments that would be inspected
on a biennial basis (1,561/2 = 781) by a FDA Inspector at an average grade of GS-13/5. The
estimated time include inspection, reviewing records and writing up a report. There are
approximately 657 (2,218 – 1,561 = 657) reproductive HCT/P establishments that would be
inspected for compliance with the donor eligibility requirements every 4 years (164 (657/4) per
year). This cost is also based on FDA regulatory review staff who process and review the
requests for exemptions or alternatives. The salary estimates include benefits but no overhead
costs.
15. Explanation for Program Changes or Adjustments
The agency has adjusted its estimate to reflect an increase of 509,539 in annual responses and
5,397,434 in annual hours. We attribute the change to an increase in third party disclosures and
the addition of nominal burden approved under OMB Control No. 0910-0829 resulting from
rulemaking (an increase of 4,225 responses and 1,919 hours from revised registration and listing
requirements).
16. Plans for Tabulation and Publication and Project Time Schedule
The agency has no such plans.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of OMB expiration date is appropriate.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.