0456 Xenotransplantation SSA 2019 Ext

UNITED STATES FOOD & DRUG ADMINISTRATION
Public Health Service Guideline on
Infectious Disease Issues in Xenotransplantation
OMB Control No. 0910-0456
SUPPORTING STATEMENT Part A – Justification:
1. Circumstances Making the Collection of Information Necessary
This information collection supports implementation of sections 351 and 361 of the Public
Health Service Act (PHS Act) (42 U.S.C. 262 and 264) and certain drug provisions of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.). In the Federal Register of
January 29, 2001 (66 FR 8120), the Food and Drug Administration (FDA, us or we) announced
the availability of the “PHS Guideline on Infectious Disease Issues in Xenotransplantation.”
The guideline was developed by the PHS to identify general principles for the prevention and
control of infectious diseases associated with xenotransplantation that may pose a risk to public
health. The PHS guideline recommends procedures to diminish the risk of transmission of
infectious agents to the xenotransplantation product recipient and to the general public.
In 2001, FDA on behalf of PHS announced the PHS Guideline to address the infectious disease
concerns raised by xenotransplantation. The PHS Guideline was jointly developed by agencies
within the Department of Health and Human Services (DHHS), including FDA, the Centers for
Disease Control and Prevention, the Health Resources and Services Administration, the National
Institutes of Health, all parts of PHS as well as the DHHS Office of the Assistant Secretary for
Planning and Evaluation. The PHS Guideline is intended to protect the public health and help
ensure the safety of using xenotransplantation products in humans by preventing the
introduction, transmission, and spread of infectious diseases associated with xenotransplantation.
The PHS Guideline covers information collection provisions including notification of certain
information to FDA or to sponsors, and documentation of certain information associated with
xenotransplantation. The collections of information are intended to provide general guidance on
the following topics: (1) The development of xenotransplantation clinical protocols, (2) the
preparation of submissions to FDA, and (3) the conduct of xenotransplantation clinical trials.
Also, the collections of information are intended to help ensure that the sponsor maintains
important information in a cross-referenced system that links the relevant records of the
xenotransplantation product recipient, xenotransplantation product, source animal(s), animal
procurement center, and significant nosocomial exposures. The PHS Guideline also describes an
occupational health service program for the protection of health care workers involved in
xenotransplantation procedures, caring for xenotransplantation product recipients, and
performing associated laboratory testing.
Accordingly, we request OMB approval of the information provisions found in the PHS
Guideline as discussed in this supporting statement.

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2. Purpose and Use of the Information Collection
The PHS guideline is intended to address public health issues raised by xenotransplantation,
through identification of general principles of prevention and control of infectious diseases
associated with xenotransplantation that may pose a hazard to the public health. Respondents to
the collection are sponsors of clinical studies of investigational xenotransplantation products
under investigational new drug applications (INDs) and xenotransplantation product
procurement centers, referred to as source animal facilities.
3. Use of Improved Information Technology and Burden Reduction
Respondents to the information collection may use computerized storage e.g., (tapes, discs, etc.),
microfiche or microfilm to record and store data and information rather than hard copy records if
they choose. Notification can be made by phone, fax, or mail. Although we are unaware of any
other improved technology to further reduce the burden, we continue to pursue methods of
applying technology to further reduce the burden to the respondents of the collection of
information.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. The provisions of the PHS Guideline
uniquely apply to Infectious Disease Issues in Xenotransplantation.
5. Impact on Small Businesses or Other Small Entities
The information collection imposes no undue burden on small entities. At the same time,
assistance is available to small business entities through our Center for Biologics Evaluation and
Research’s (CBER’s) Office of Communication, Outreach, and Development, Division of
Manufacturers Assistance and Training, as well as through resources available from our website.
6. Consequences of Collecting the Information Less Frequently
The information collection schedule recommended is intended to diminish the risk of
transmission of infectious agents to the xenotransplantation product recipient, to health care
workers, and to the general public. Less frequent collection of information would not provide
the necessary information needed to help prevent the transmission of infectious agents to
xenotransplantation products recipients, to health care workers and to the general public.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
Because xenotransplantation is a unique area of medical science where potential problems and
adverse effects continue to be revealed. Due to the potential risk for cross-species transmission
of pathogenic persistent virus, the PHS Guideline recommends that health records be retained for
50 years. We regard these records as “[f]acts or opinions obtained initially or in follow-on
requests, from individuals (including individuals in control groups) under treatment or clinical
examination” (5 CFR 1320.3(h)(5)) and therefore not subject to OMB review. The retention

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period is intended to assist health care practitioners and officials in surveillance and tracking
sources of infection, disease, or illness that might emerge in recipients, the source animal, or the
animal herd or colony after a xenotransplantation.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside Agency
In accordance with 5 CFR 1320.8(d), we published a 60-day notice inviting public comment in
the Federal Register of September 25, 2018 (83 FR 48441). No comments were received.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift is provided to respondents.
10. Assurance of Confidentiality Provided to Respondents
Proprietary trade secret or other confidential information may be submitted consistent with
provisions found in the guideline. The confidentiality of information received by FDA is
consistent with the Freedom of Information Act (FOIA) and the agency’s published regulations
of “Public Information” under 21 CFR Part 20.
11. Justification for Sensitive Questions
There are no questions of a sensitive nature associated with the information collection.
12. Estimates of Annualized Burden and Costs
We estimate the burden for the information collection as follows:
12a. Annualized Hour Burden Estimate
The total estimated annual hourly burden is 59.03, as reflected in the tables below:
Table 1 – Estimated Annual Reporting Burden1
PHS Guideline Section; Information
No. of
No. of
Total
Avg. Burden Total
Collection Activity
Respondents
Responses per
Annual
per
Hours
Respondent
Responses
Response
3.2.7.2; Notify sponsor or FDA of new
1
1
1
0.50
0.5
archive site when the source animal facility
(30 mins.)
or sponsor ceases operations.2
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
2
FDA is using 1 animal facility or sponsor for estimation purposes.

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Table 2 – Estimated Annual Recordkeeping Burden1
PHS Guideline Section; Information
Collection Activity

No. of
Recordkeepers

No. of
Records per
Recordkeeper
1

Total
Annual
Records
1

Avg. Burden
per
Recordkeeping
16

Total
Hours

3.2.7; Establish records linking each
1
16
xenotransplantation product recipient with
relevant records.2
4.3; Sponsor to maintain cross-referenced
3
1
3
0.75
2.25
system that links all relevant records
(45 mins.)
(recipient, product, source animal, animal
procurement center, and nosocomial
exposures).3
3.4.2; Document results of monitoring
3
10.67
32
0.25
8
program used to detect introduction of
(15 mins.)
infectious agents which may not be
apparent clinically.4
3.4.3.2; Document full necropsy
3
2.67
8
0.25
2
investigations including evaluation for
(15 mins.)
infectious etiologies.5
3.5.1; Justify shortening a source animal’s
3
0.33
1
0.50
0.5
quarantine period of 3 weeks prior to
(30 mins.)
xenotransplantation product procurement.6
3.5.2; Document absence of infectious
3
0.33
1
0.25
0.25
agent in xenotransplantation product if its
(15 mins.)
presence elsewhere in source animal does
not preclude using it.6
3.5.4; Add summary of individual source
3
1
3
0.17
0.51
animal record to permanent medical record
(10 mins.)
of the xenotransplantation product
recipient.
3.6.4; Document complete necropsy results
3
2.67
8
0.25
2
on source animals (50-year record
(15 mins.)
retention).7
3.7; Link xenotransplantation product
4
2
8
0.08
0.64
recipients to individual source animal
(5 mins.)
records and archived biologic specimens.7
4.2.3.2; Record baseline sera of
5
25
125
0.17 21.25
xenotransplantation health care workers
(10 mins.)
and specific nosocomial exposure.8
4.2.3.2; Record baseline sera of
5
0.20
1
0.17
0.17
xenotransplantation health care workers
(10 mins.)
and specific nosocomial exposure (no
exposure)..6
4.2.3.3 and 4.3.2; Keep a log of health care
5
0.20
1
0.17
0.17
workers’ significant nosocomial
(10 mins.)
exposure(s).6
4.3.1; Document each xenotransplant
3
1
3
0.25
0.75
procedure.
(15 mins.)
5.2; Document location and nature of
3
4
12
0.08
0.96
archived specimens in health care records
(5 mins.)
of xenotransplantation product recipient
and source animal.9
Total
55.45
1
There are no capital costs or operating and maintenance costs associated with this collection of information.

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2

A one-time burden for new respondents to set up a recordkeeping system linking all relevant records. FDA is
using 1 new sponsor for estimation purposes.
3
FDA estimates there is minimal recordkeeping burden associated with maintaining the record system.
4
Monitoring for sentinel animals (subset representative of herd) plus all source animals. There are approximately 6
sentinel animals per herd x 1 herd per facility x 4 facilities = 24 sentinel animals. There are approximately 8 source
animals per year (see footnote 7 of this table); 24 + 8 = 32 monitoring records to document.
5
Necropsy for animal deaths of unknown cause estimated to be approximately 2 per herd per year x 1 herd per
facility x 4 facilities = 8.
6
Has not occurred in the past 3 years and is expected to continue to be a rare occurrence.
7
On average 2 source animals are used for preparing xenotransplantation product material for one recipient. The
average number of source animals is 2 source animals per recipient x 4 recipients annually = 8 source animals per
year. (See footnote 5 of table 6 of this document.)
8
FDA estimates there are 5 clinical centers doing xenotransplantation procedures x approximately 25 health care
workers involved per center = 125 health care workers.
9
Eight source animal records + 4 recipient records = 12 total records.

Table 3 – Estimated Annual Third-Party Disclosure Burden1
PHS Guideline Section; Information
Collection Activity

No. of
Respondents

No. of
Disclosures per
Respondent
1

Total
Annual
Disclosures
1

Avg.
Burden per
Disclosure
0.50
(30 mins.)

Total
Hours

3.2.7.2; Notify sponsor or FDA of new
1
archive site when the source animal facility
0.5
or sponsor ceases operations.2
3.4; Standard operating procedures (SOPs)
4
0.25
1
0.08
of source animal facility should be
(5 mins.)
0.08
available to review bodies.3
3.5.1; Include increased infectious risk in
4
0.25
1
0.25
informed consent if source animal
(15 mins.)
0.25
quarantine period of 3 weeks is shortened.4
3.5.4; Sponsor to make linked records
4
1
4
0.50
described in section 3.2.7 available for
(30 mins.)
2
review.5
3.5.5; Source animal facility to notify
4
0.25
1
0.25
clinical center when infectious agent is
(15 mins.)
0.25
identified in source animal or herd after
xenotransplantation product procurement.4
Total
3.08
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
2
FDA is using 1 animal facility or sponsor for estimation purposes.
3
FDA’s records indicate that an average of 1 INDs are expected to be submitted per year.
4
To our knowledge, has not occurred in the past 3 years and is expected to continue to be a rare occurrence.
5
Based on an estimate of 12 patients treated over a 3 year period, the average number of xenotransplantation product
recipients per year is estimated to be 4.

Respondents to this collection of information are sponsors of clinical studies of investigational
xenotransplantation products under investigational new drug applications (INDs) and
xenotransplantation product procurement centers, referred to as source animal facilities. There
are an estimated three respondents who are sponsors of INDs that include protocols for
xenotransplantation in humans and five clinical centers doing xenotransplantation procedures.
Other respondents for this collection of information are an estimated four source animal facilities
which provide source xenotransplantation product material to sponsors for use in human

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xenotransplantation procedures. These four source animal facilities keep medical records of the
herds/colonies as well as the medical records of the individual source animal(s). The burden
estimates are based on FDA's records of xenotransplantation-related INDs and estimates of time
required to complete the various reporting, recordkeeping, and third-party disclosure tasks
described in the PHS guideline.
12b. Annualized Cost Burden Estimate
The estimated annual cost burden is $3,921.04, as reflected below.
Activity
Reporting
Recordkeeping
Disclosure
TOTAL

Total Burden Hours
0.50
55.45
3.08

Hourly Wage Rate
$73.00
$66.00
$73.00

Total Cost
$36.50
$3,659.70
$224.84
$3,921.04

The reporting cost estimate is based on an average pay rate of $73.00/hour. This average is
based on the salaries of an upper-level manager, mid-level professional, and clerical support who
may be involved in notifying or providing any necessary information. The recordkeeping cost
estimate is based on an average pay rate of $66.00/hour of a study coordinator and clinical
investigator who are involved with the documentation and maintenance of records. The salary
estimates include benefits but no overhead costs.
13. Estimates of Other Total Annual Cost Burden to Respondents or Recordkeepers
There are no capital, start-up, operating or maintenance costs associated with this information
collection.
14. Annualized Cost to the Federal Government
Costs to FDA covers the allocation of two investigators at an average cost commensurate with
the pay of a grade scale (GS)-13 ($58.00/hr) who perform on-site inspections. The salary
estimate includes benefits but no overhead costs. The cost is also based on an average time to
inspect a facility, review the records, and prepare an establishment inspection report. Based on
our experience with the collection, we expect to incur costs for one inspection annually.
Cumulatively therefore, the total cost is $4,640.00 (1 inspection utilizing 2 investigators @
$58/hr. for 40 hours = $4,640.00)
15. Explanation for Program Changes or Adjustments
Based on our evaluation of the information collection, we are retaining the currently approved
burden estimate. At the same time, we have consolidated the itemized listing of IC elements into
three discrete ICs reflecting notification (reporting), recordkeeping, and disclosure. Finally, we
have uploaded costs found in Question 12b, previously and currently included, so that they are
reflected at www.reginfo.gov for easier reference by our readers.

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16. Plans for Tabulation and Publication and Project Time Schedule
We have no such plans for the information collection.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
The OMB expiration date will be displayed as required.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.