Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation, 18551-18555 [2019-08845]
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18551
Federal Register / Vol. 84, No. 84 / Wednesday, May 1, 2019 / Notices
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1—Continued
Number of
disclosures
per
respondent
Number of
respondents
Activity/21 CFR section
Provisional mammography facility
certificate extension application—900.11(b)(3).
Mammography facility certificate
reinstatement
application—
900.11(c).
Lay summary of examination—
900.12(c)(2).
Lay summary of examination; patient refusal 5—900.12(c)(2).
Report of unresolved serious complaints—900.12(h)(4).
Information regarding compromised
quality; facility 3—900.12(j)(1).
Information regarding compromised
quality; AB 4—900.12(j)(1).
Patient notification of serious risk—
900.12(j)(2).
Reconsideration of accreditation—
900.15(c).
Notification of requirement to correct
major
deficiencies—
900.24(a).
Notification of loss of approval;
major deficiencies—900.24(a)(2).
Notification of probationary status—900.24(b)(1).
Notification of loss of approval;
minor deficiencies—900.24(b)(3).
Total ........................................
Average
burden per
disclosure
Total annual
disclosures
Total hours 2
Total
operating and
maintenance
costs
0
1
0
0.5 (30 minutes) ......
1
312
1
312
5 ..............................
1,560
8,654
5,085
44,055,590
0.083 (5 minutes) ....
3,652,464
87
1
87
0.5 (30 minutes) ......
44
20
1
20
1 ..............................
20
20
1
20
200 ..........................
4,000
324
20
1
20
320 ..........................
6,400
646
5
1
5
100 ..........................
500
20,878
5
1
5
2 ..............................
10
0.4
1
0.4
200 ..........................
80
73
0.15
1
0.15
100 ..........................
15
27
0.3
1
0.3
200 ..........................
60
55
0.15
1
0.15
100 ..........................
15
27
........................
........................
........................
.................................
3,691,842
26,141,344
25,861,265
1 There
are no capital costs associated with the collection of information.
hours have been rounded.
to the facility component of the burden for this requirement.
4 Refers to the AB component of the burden for this requirement.
5 Refers to the situation where a patient specifically does not want to receive the lay summary of her exam.
2 Total
3 Refers
FDA has adjusted the number of
respondents for § 900.3(c) ‘‘AB renewal
of approval’’ to one. This adjustment
resulted in a 14-hour increase to the
hour-burden estimate. Additionally, we
updated the capital costs and operating
and maintenance costs by adjusting
them for inflation since the last update
to those estimates. This adjustment
resulted in a $1,893,071 increase to the
estimated capital and operating and
maintenance costs ($24,410,106
previously; $26,303,177 current
extension request).
Dated: April 24, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–08784 Filed 4–30–19; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2012–N–0559]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Public Health
Service Guideline on Infectious
Disease Issues in Xenotransplantation
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by May 31,
2019.
SUMMARY:
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To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0456. Also
include the FDA docket number found
in brackets in the heading of this
document.
ADDRESSES:
FOR FURTHER INFORMATION CONTACT:
JonnaLynn Capezzuto, Office of
Operations, Food and Drug
Administration, Three White Flint
North, 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
3794, PRAStaff@fda.hhs.gov.
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
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Federal Register / Vol. 84, No. 84 / Wednesday, May 1, 2019 / Notices
Public Health Service Guideline on
Infectious Disease Issues in
Xenotransplantation
OMB Control Number 0910–0456—
Extension
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The statutory authority to collect this
information is provided under sections
351 and 361 of the Public Health
Service (PHS) Act (42 U.S.C. 262 and
264) and the provisions of the Federal
Food, Drug, and Cosmetic Act that
apply to drugs (21 U.S.C. 321 et seq.).
In the Federal Register of January 29,
2001 (66 FR 8120), FDA 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. 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. The
collection of information described in
this guideline is 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 collection of information will help
ensure that the sponsor maintains
important information in a crossreferenced 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 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. The PHS guideline is intended
to protect the public health and to 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 also recommends
that certain specimens and records be
maintained for 50 years beyond the date
of the xenotransplantation. These
include: (1) Records linking each
xenotransplantation product recipient
with relevant health records of the
source animal, herd or colony, and the
specific organ, tissue, or cell type
included in or used in the manufacture
of the product (3.2.7.1); (2) aliquots of
serum samples from randomly selected
animal and specific disease
investigations (3.4.3.1); (3) source
animal biological specimens designated
for PHS use (3.7.1); animal health
records (3.7.2), including necropsy
results (3.6.4); and (4) recipients’
biological specimens (4.1.2). The
retention period is intended to assist
health care practitioners and officials in
surveillance and in tracking the source
of an infection, disease, or illness that
might emerge in the recipient, the
source animal, or the animal herd or
colony after a xenotransplantation.
The recommendation for maintaining
records for 50 years is based on clinical
experience with several human viruses
that have presented problems in human
to human transplantation and are
therefore thought to share certain
characteristics with viruses that may
pose potential risks in
xenotransplantation. These
characteristics include long latency
periods and the ability to establish
persistent infections. Several also share
the possibility of transmission among
individuals through intimate contact
with human body fluids. Human
immunodeficiency virus (HIV) and
Human T-lymphotropic virus are
human retroviruses. Retroviruses
contain ribonucleic acid that is reversetranscribed into deoxyribonucleic acid
(DNA) using an enzyme provided by the
virus and the human cell machinery.
That viral DNA can then be integrated
into the human cellular DNA. Both
viruses establish persistent infections
and have long latency periods before the
onset of disease, 10 years and 40 to 60
years, respectively. The human hepatitis
viruses are not retroviruses, but several
share with HIV the characteristic that
they can be transmitted through body
fluids, can establish persistent
infections, and have long latency
periods, e.g., approximately 30 years for
Hepatitis C.
In addition, the PHS guideline
recommends that a record system be
developed that allows easy, accurate,
and rapid linkage of information among
the specimen archive, the recipient’s
medical records, and the records of the
source animal for 50 years. The
development of such a record system is
a one-time burden. Such a system is
intended to cross-reference and locate
relevant records of recipients, products,
source animals, animal procurement
centers, and significant nosocomial
exposures.
Respondents to this collection of
information are the 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
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.
In the Federal Register of September
25, 2018 (83 FR 48441), FDA published
a 60-day notice requesting public
comment on the proposed collection of
information. No comments were
received.
FDA is requesting an extension of
OMB approval for the following
reporting, recordkeeping, and thirdparty disclosure recommendations in
the PHS guideline:
TABLE 1—REPORTING RECOMMENDATIONS
PHS guideline section
Description
3.2.7.2 .............................................
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Notify sponsor or FDA of new archive site when the source animal facility or sponsor ceases operations.
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Federal Register / Vol. 84, No. 84 / Wednesday, May 1, 2019 / Notices
TABLE 2—RECORDKEEPING RECOMMENDATIONS
PHS guideline section
Description
3.2.7 ................................................
4.3 ...................................................
Establish records linking each xenotransplantation product recipient with relevant records.
Sponsor to maintain cross-referenced system that links all relevant records (recipient, product, source animal, animal procurement center, and nosocomial exposures).
Document results of monitoring program used to detect introduction of infectious agents which may not be
apparent clinically.
Document full necropsy investigations including evaluation for infectious etiologies.
Justify shortening a source animal’s quarantine period of 3 weeks prior to xenotransplantation product procurement.
Document absence of infectious agent in xenotransplantation product if its presence elsewhere in source
animal does not preclude using it.
Add summary of individual source animal record to permanent medical record of the xenotransplantation
product recipient.
Document complete necropsy results on source animals (50-year record retention).
Link xenotransplantation product recipients to individual source animal records and archived biologic specimens.
Record baseline sera of xenotransplantation health care workers and specific nosocomial exposure.
Keep a log of health care workers’ significant nosocomial exposure(s).
Document each xenotransplant procedure.
Document location and nature of archived specimens in health care records of xenotransplantation product
recipient and source animal.
3.4.2 ................................................
3.4.3.2 .............................................
3.5.1 ................................................
3.5.2 ................................................
3.5.4 ................................................
3.6.4 ................................................
3.7 ...................................................
4.2.3.2 .............................................
4.2.3.3 and 4.3.2 .............................
4.3.1 ................................................
5.2 ...................................................
TABLE 3—DISCLOSURE RECOMMENDATIONS
PHS guideline section
Description
3.2.7.2 .............................................
3.4 ...................................................
3.5.1 ................................................
Notify sponsor or FDA of new archive site when the source animal facility or sponsor ceases operations.
Standard operating procedures (SOPs) of source animal facility should be available to review bodies.
Include increased infectious risk in informed consent if source animal quarantine period of 3 weeks is
shortened.
Sponsor to make linked records described in section 3.2.7 available for review.
Source animal facility to notify clinical center when infectious agent is identified in source animal or herd
after xenotransplantation product procurement.
3.5.4 ................................................
3.5.5 ................................................
FDA estimates the burden for this
collection of information as follows:
TABLE 4—ESTIMATED ANNUAL REPORTING BURDEN 1
PHS guideline section
Number of
respondents
Number of responses
per respondent
Total annual
responses
Average burden
per response
Total hours
3.2.7.2 2 .......................
1
1
1
0.50 (30 minutes) ........
0.5
1 There
2 FDA
are no capital costs or operating and maintenance costs associated with this collection of information.
is using 1 animal facility or sponsor for estimation purposes.
TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
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PHS guideline section
3.2.7 2 ................................................
4.3 3 ...................................................
3.4.2 4 ................................................
3.4.3.2 5 .............................................
3.5.1 6 ................................................
3.5.2 6 ................................................
3.5.4 ..................................................
3.6.4 7 ................................................
3.7 7 ...................................................
4.2.3.2 8 .............................................
4.2.3.2 6 .............................................
4.2.3.3 and 4.3.2 6 ............................
4.3.1 ..................................................
5.2 9 ...................................................
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Number of
records
per recordkeeper
1
3
3
3
3
3
3
3
4
5
5
5
3
3
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Total annual
records
1
1
10.67
2.67
0.33
0.33
1
2.67
2
25
0.20
0.20
1
4
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1
3
32
8
1
1
3
8
8
125
1
1
3
12
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Average burden
per
recordkeeping
16 ......................................................
0.75 (45 minutes) .............................
0.25 (15 minutes) .............................
0.25 (15 minutes) .............................
0.50 (30 minutes) .............................
0.25 (15 minutes) .............................
0.17 (10 minutes) .............................
0.25 (15 minutes) .............................
0.08 (5 minutes) ...............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.25 (15 minutes) .............................
0.08 (5 minutes) ...............................
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Total hours
16
2.25
8
2
0.5
0.25
0.51
2
0.64
21.25
0.17
0.17
0.75
0.96
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Federal Register / Vol. 84, No. 84 / Wednesday, May 1, 2019 / Notices
TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1—Continued
PHS guideline section
Total ...........................................
Number of
recordkeepers
Number of
records
per recordkeeper
Total annual
records
Average burden
per
recordkeeping
........................
........................
........................
...........................................................
Total hours
55.45
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
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 ×
1 herd per facility × 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 × 1 herd per facility × 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 × 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 × approximately 25 health care workers involved per center
= 125 health care workers.
9 Eight source animal records + 4 recipient records = 12 total records.
TABLE 6—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
disclosures
per
respondent
Number of
respondents
PHS guideline section
Total annual
disclosures
Average burden
per disclosure
3.2.7.2 2 .............................................
3.4 3 ...................................................
3.5.1 4 ................................................
3.5.4 5 ................................................
3.5.5 4 ................................................
1
4
4
4
4
1
0.25
0.25
1
0.25
1
1
1
4
1
Total ...........................................
........................
........................
........................
0.50
0.08
0.25
0.50
0.25
Total hours
(30 minutes) .............................
(5 minutes) ...............................
(15 minutes) .............................
(30 minutes) .............................
(15 minutes) .............................
0.5
0.08
0.25
2
0.25
...........................................................
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.
Because of the potential risk for crossspecies transmission of pathogenic
persistent virus, the guideline
recommends that health records be
retained for 50 years. Since these
records are medical records, the
retention of such records for up to 50
years is not information subject to the
PRA (5 CFR 1320.3(h)(5)). Also, because
of the limited number of clinical studies
with small patient populations, the
number of records is expected to be
insignificant at this time.
Information collections in this
guideline not included in tables 1
through 6 can be found under existing
regulations and approved under the
OMB control numbers as follows: (1)
‘‘Current Good Manufacturing Practice
for Finished Pharmaceuticals,’’ 21 CFR
211.1 through 211.208, approved under
OMB control number 0910–0139; (2)
‘‘Investigational New Drug
Application,’’ 21 CFR 312.1 through
312.160, approved under OMB control
number 0910–0014; and (3) information
included in a biologics license
application, 21 CFR 601.2, approved
under OMB control number 0910–0338.
(Although it is possible that a
xenotransplantation product may not be
regulated as a biological product (e.g., it
may be regulated as a medical device),
FDA believes, based on its knowledge
and experience with
xenotransplantation, that any
xenotransplantation product subject to
FDA regulation within the next 3 years
will most likely be regulated as a
biological product.) However, FDA
recognized that some of the information
collections go beyond approved
collections; assessments for these
burdens are included in tables 1 through
6.
In table 7, FDA identifies those
collection of information activities that
are already encompassed by existing
regulations or are consistent with
voluntary standards which reflect
industry’s usual and customary business
practice.
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TABLE 7—COLLECTION OF INFORMATION REQUIRED BY CURRENT REGULATIONS AND STANDARDS
21 CFR section
(unless otherwise stated)
PHS guideline section
Description of collection of information activity
2.2.1 ................................................
2.5 ...................................................
3.1.1 and 3.1.6 ................................
Document off-site collaborations ...........................................................
Sponsor ensures counseling patient + family + contacts .....................
Document well-characterized health history and lineage of source
animals.
Registration with and import permit from the Centers for Disease
Control and Prevention.
3.1.8 ................................................
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312.52.
312.62(c).
312.23(a)(7)(a) and 211.84.
42 CFR 71.53.
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TABLE 7—COLLECTION OF INFORMATION REQUIRED BY CURRENT REGULATIONS AND STANDARDS—Continued
PHS guideline section
Description of collection of information activity
21 CFR section
(unless otherwise stated)
3.2.2 ................................................
3.2.3 ................................................
Document collaboration with accredited microbiology labs ..................
Procedures to ensure the humane care of animals ..............................
3.2.4 ................................................
Procedures consistent for accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and consistent with the National
Research Council’s (NRC) Guide.
Herd health maintenance and surveillance to be documented, available, and in accordance with documented procedures; record
standard veterinary care.
Animal facility SOPs ..............................................................................
Validate assay methods ........................................................................
Procurement and processing of xenografts using documented aseptic
conditions.
Develop, implement, and enforce SOP’s for procurement and screening processes.
Communicate to FDA animal necropsy findings pertinent to health of
recipient.
PHS specimens to be linked to health records; provide to FDA justification for types of tissues, cells, and plasma, and quantities of
plasma and leukocytes collected.
Surveillance of xenotransplant recipient; sponsor ensures documentation of surveillance program life-long (justify >2 yrs.); investigator
case histories (2 yrs. after investigation is discontinued).
Sponsor to justify amount and type of reserve samples .......................
System for prompt retrieval of PHS specimens and linkage to medical
records (recipient and source animal).
Notify FDA of a clinical episode potentially representing a xenogeneic
infection.
Document collaborations (transfer of obligation) ...................................
Develop educational materials (sponsor provides investigators with
information needed to conduct investigation properly).
Sponsor to keep records of receipt, shipment, and disposition of investigative drug; investigator to keep records of case histories.
312.52.
9 CFR parts 1, 2, and 3 and PHS
Policy.1
AAALAC International Rules of Accreditation 2 and NRC Guide.3
3.2.5, 3.4, and 3.4.1 ........................
3.2.6 ................................................
3.3.3 ................................................
3.6.1 ................................................
3.6.2 ................................................
3.6.4 ................................................
3.7.1 ................................................
4.1.1 ................................................
4.1.2 ................................................
4.1.2.2 .............................................
4.1.2.3 .............................................
4.2.2.1 .............................................
4.2.3.1 .............................................
4.3 ...................................................
211.100 and 211.122.
PHS Policy.1
211.160(a).
211.100 and 211.122.
211.84(d) and 211.122(c).
312.32(c).
312.23(a)(6).
312.23(a)(6)(iii)(f) and
312.62(b) and (c).
(g),
and
211.122.
312.57(a).
312.32.
312.52.
312.50.
312.57 and 312.62(b).
1 The ‘‘Public Health Service Policy on Humane Care and Use of Laboratory Animals’’ (https://www.grants.nih.gov/grants/olaw/references/
phspol.htm).
2 AAALAC International Rules of Accreditation (https://www.aaalac.org/accreditation/rules.cfm).
3 The NRC’s ‘‘Guide for the Care and Use of Laboratory Animals.’’
Based on a review of the information
collection since our last request for
OMB approval, we have made no
adjustments to our burden estimate.
Dated: April 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–08845 Filed 4–30–19; 8:45 am]
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Comments regarding this
information collection are best assured
of having their full effect if received
within 60 days of the date of this
publication.
National Institutes of Health
FOR FURTHER INFORMATION CONTACT:
DATES:
BILLING CODE 4164–01–P
Proposed Collection; 60-Day Comment
Request; NIH Information Collection
Forms To Support Genomic Data
Sharing for Research Purposes (OD)
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for public comment on proposed data
collection projects, the National
Institutes of Health Office of the
Director (OD) will publish periodic
summaries of proposed projects to be
submitted to the Office of Management
and Budget (OMB) for review and
approval.
AGENCY:
National Institutes of Health,
HHS.
ACTION:
Notice.
In compliance with the
requirement of the Paperwork
Reduction Act of 1995, for opportunity
SUMMARY:
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To
obtain a copy of the data collection
plans and instruments, submit
comments in writing, or request more
information on the proposed project,
contact: Dr. Lyric A. Jorgenson, Acting
Director, Division of Scientific Data
Sharing Policy, Office of Science Policy,
NIH, 6705 Rockledge Dr., Suite 750,
Bethesda, MD 20892, or call non-tollfree number (301) 496–9838 or email
your request including your address to:
SciencePolicy@mail.nih.gov Formal
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requests for additional plans and
instruments must be requested in
writing.
Section
3506(c)(2)(A) of the Paperwork
Reduction Act of 1995 requires: Written
comments and/or suggestions from the
public and affected agencies are invited
to address one or more of the following
points: (1) Whether the proposed
collection of information is necessary
for the proper performance of the
function of the agency, including
whether the information will have
practical utility; (2) The accuracy of the
agency’s estimate of the burden of the
proposed collection of information,
including the validity of the
methodology and assumptions used; (3)
Ways to enhance the quality, utility, and
clarity of the information to be
collected; and (4) Ways to minimize the
burden of the collection of information
from those who are to respond,
including the use of appropriate
automated, electronic, mechanical, or
other technological collection
SUPPLEMENTARY INFORMATION:
E:\FR\FM\01MYN1.SGM
01MYN1
]]>Agencies
[Federal Register Volume 84, Number 84 (Wednesday, May 1, 2019)]
[Notices]
[Pages 18551-18555]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-08845]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0559]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Public Health Service
Guideline on Infectious Disease Issues in Xenotransplantation
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by May 31,
2019.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or emailed to [email protected]. All
comments should be identified with the OMB control number 0910-0456.
Also include the FDA docket number found in brackets in the heading of
this document.
FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794,
[email protected].
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
[[Page 18552]]
Public Health Service Guideline on Infectious Disease Issues in
Xenotransplantation
OMB Control Number 0910-0456--Extension
The statutory authority to collect this information is provided
under sections 351 and 361 of the Public Health Service (PHS) Act (42
U.S.C. 262 and 264) and the provisions of the Federal Food, Drug, and
Cosmetic Act that apply to drugs (21 U.S.C. 321 et seq.). In the
Federal Register of January 29, 2001 (66 FR 8120), FDA 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. 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. The
collection of information described in this guideline is 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 collection of information will 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 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. The PHS guideline is intended
to protect the public health and to 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 also recommends that certain specimens and
records be maintained for 50 years beyond the date of the
xenotransplantation. These include: (1) Records linking each
xenotransplantation product recipient with relevant health records of
the source animal, herd or colony, and the specific organ, tissue, or
cell type included in or used in the manufacture of the product
(3.2.7.1); (2) aliquots of serum samples from randomly selected animal
and specific disease investigations (3.4.3.1); (3) source animal
biological specimens designated for PHS use (3.7.1); animal health
records (3.7.2), including necropsy results (3.6.4); and (4)
recipients' biological specimens (4.1.2). The retention period is
intended to assist health care practitioners and officials in
surveillance and in tracking the source of an infection, disease, or
illness that might emerge in the recipient, the source animal, or the
animal herd or colony after a xenotransplantation.
The recommendation for maintaining records for 50 years is based on
clinical experience with several human viruses that have presented
problems in human to human transplantation and are therefore thought to
share certain characteristics with viruses that may pose potential
risks in xenotransplantation. These characteristics include long
latency periods and the ability to establish persistent infections.
Several also share the possibility of transmission among individuals
through intimate contact with human body fluids. Human immunodeficiency
virus (HIV) and Human T-lymphotropic virus are human retroviruses.
Retroviruses contain ribonucleic acid that is reverse-transcribed into
deoxyribonucleic acid (DNA) using an enzyme provided by the virus and
the human cell machinery. That viral DNA can then be integrated into
the human cellular DNA. Both viruses establish persistent infections
and have long latency periods before the onset of disease, 10 years and
40 to 60 years, respectively. The human hepatitis viruses are not
retroviruses, but several share with HIV the characteristic that they
can be transmitted through body fluids, can establish persistent
infections, and have long latency periods, e.g., approximately 30 years
for Hepatitis C.
In addition, the PHS guideline recommends that a record system be
developed that allows easy, accurate, and rapid linkage of information
among the specimen archive, the recipient's medical records, and the
records of the source animal for 50 years. The development of such a
record system is a one-time burden. Such a system is intended to cross-
reference and locate relevant records of recipients, products, source
animals, animal procurement centers, and significant nosocomial
exposures.
Respondents to this collection of information are the 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 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.
In the Federal Register of September 25, 2018 (83 FR 48441), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
FDA is requesting an extension of OMB approval for the following
reporting, recordkeeping, and third-party disclosure recommendations in
the PHS guideline:
Table 1--Reporting Recommendations
------------------------------------------------------------------------
PHS guideline section Description
------------------------------------------------------------------------
3.2.7.2........................... Notify sponsor or FDA of new archive
site when the source animal
facility or sponsor ceases
operations.
------------------------------------------------------------------------
[[Page 18553]]
Table 2--Recordkeeping Recommendations
------------------------------------------------------------------------
PHS guideline section Description
------------------------------------------------------------------------
3.2.7............................. Establish records linking each
xenotransplantation product
recipient with relevant records.
4.3............................... Sponsor to maintain cross-referenced
system that links all relevant
records (recipient, product, source
animal, animal procurement center,
and nosocomial exposures).
3.4.2............................. Document results of monitoring
program used to detect introduction
of infectious agents which may not
be apparent clinically.
3.4.3.2........................... Document full necropsy
investigations including evaluation
for infectious etiologies.
3.5.1............................. Justify shortening a source animal's
quarantine period of 3 weeks prior
to xenotransplantation product
procurement.
3.5.2............................. Document absence of infectious agent
in xenotransplantation product if
its presence elsewhere in source
animal does not preclude using it.
3.5.4............................. Add summary of individual source
animal record to permanent medical
record of the xenotransplantation
product recipient.
3.6.4............................. Document complete necropsy results
on source animals (50-year record
retention).
3.7............................... Link xenotransplantation product
recipients to individual source
animal records and archived
biologic specimens.
4.2.3.2........................... Record baseline sera of
xenotransplantation health care
workers and specific nosocomial
exposure.
4.2.3.3 and 4.3.2................. Keep a log of health care workers'
significant nosocomial exposure(s).
4.3.1............................. Document each xenotransplant
procedure.
5.2............................... Document location and nature of
archived specimens in health care
records of xenotransplantation
product recipient and source
animal.
------------------------------------------------------------------------
Table 3--Disclosure Recommendations
------------------------------------------------------------------------
PHS guideline section Description
------------------------------------------------------------------------
3.2.7.2........................... Notify sponsor or FDA of new archive
site when the source animal
facility or sponsor ceases
operations.
3.4............................... Standard operating procedures (SOPs)
of source animal facility should be
available to review bodies.
3.5.1............................. Include increased infectious risk in
informed consent if source animal
quarantine period of 3 weeks is
shortened.
3.5.4............................. Sponsor to make linked records
described in section 3.2.7
available for review.
3.5.5............................. Source animal facility to notify
clinical center when infectious
agent is identified in source
animal or herd after
xenotransplantation product
procurement.
------------------------------------------------------------------------
FDA estimates the burden for this collection of information as
follows:
Table 4--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
PHS guideline section Number of responses per Total annual Average burden per response Total hours
respondents respondent responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
3.2.7.2 \2\.............................. 1 1 1 0.50 (30 minutes)........................ 0.5
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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.
Table 5--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Average burden
PHS guideline section Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
3.2.7 \2\..................... 1 1 1 16.............. 16
4.3 \3\....................... 3 1 3 0.75 (45 2.25
minutes).
3.4.2 \4\..................... 3 10.67 32 0.25 (15 8
minutes).
3.4.3.2 \5\................... 3 2.67 8 0.25 (15 2
minutes).
3.5.1 \6\..................... 3 0.33 1 0.50 (30 0.5
minutes).
3.5.2 \6\..................... 3 0.33 1 0.25 (15 0.25
minutes).
3.5.4......................... 3 1 3 0.17 (10 0.51
minutes).
3.6.4 \7\..................... 3 2.67 8 0.25 (15 2
minutes).
3.7 \7\....................... 4 2 8 0.08 (5 minutes) 0.64
4.2.3.2 \8\................... 5 25 125 0.17 (10 21.25
minutes).
4.2.3.2 \6\................... 5 0.20 1 0.17 (10 0.17
minutes).
4.2.3.3 and 4.3.2 \6\......... 5 0.20 1 0.17 (10 0.17
minutes).
4.3.1......................... 3 1 3 0.25 (15 0.75
minutes).
5.2 \9\....................... 3 4 12 0.08 (5 minutes) 0.96
---------------------------------------------------------------------------------
[[Page 18554]]
Total..................... .............. .............. .............. ................ 55.45
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\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 6--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
PHS guideline section Number of disclosures Total annual Average burden Total hours
respondents per respondent disclosures per disclosure
----------------------------------------------------------------------------------------------------------------
3.2.7.2 \2\................... 1 1 1 0.50 (30 0.5
minutes).
3.4 \3\....................... 4 0.25 1 0.08 (5 minutes) 0.08
3.5.1 \4\..................... 4 0.25 1 0.25 (15 0.25
minutes).
3.5.4 \5\..................... 4 1 4 0.50 (30 2
minutes).
3.5.5 \4\..................... 4 0.25 1 0.25 (15 0.25
minutes).
---------------------------------------------------------------------------------
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.
Because of the potential risk for cross-species transmission of
pathogenic persistent virus, the guideline recommends that health
records be retained for 50 years. Since these records are medical
records, the retention of such records for up to 50 years is not
information subject to the PRA (5 CFR 1320.3(h)(5)). Also, because of
the limited number of clinical studies with small patient populations,
the number of records is expected to be insignificant at this time.
Information collections in this guideline not included in tables 1
through 6 can be found under existing regulations and approved under
the OMB control numbers as follows: (1) ``Current Good Manufacturing
Practice for Finished Pharmaceuticals,'' 21 CFR 211.1 through 211.208,
approved under OMB control number 0910-0139; (2) ``Investigational New
Drug Application,'' 21 CFR 312.1 through 312.160, approved under OMB
control number 0910-0014; and (3) information included in a biologics
license application, 21 CFR 601.2, approved under OMB control number
0910-0338. (Although it is possible that a xenotransplantation product
may not be regulated as a biological product (e.g., it may be regulated
as a medical device), FDA believes, based on its knowledge and
experience with xenotransplantation, that any xenotransplantation
product subject to FDA regulation within the next 3 years will most
likely be regulated as a biological product.) However, FDA recognized
that some of the information collections go beyond approved
collections; assessments for these burdens are included in tables 1
through 6.
In table 7, FDA identifies those collection of information
activities that are already encompassed by existing regulations or are
consistent with voluntary standards which reflect industry's usual and
customary business practice.
Table 7--Collection of Information Required by Current Regulations and
Standards
------------------------------------------------------------------------
21 CFR section
Description of (unless
PHS guideline section collection of otherwise
information activity stated)
------------------------------------------------------------------------
2.2.1......................... Document off-site 312.52.
collaborations.
2.5........................... Sponsor ensures 312.62(c).
counseling patient +
family + contacts.
3.1.1 and 3.1.6............... Document well- 312.23(a)(7)(a)
characterized health and 211.84.
history and lineage
of source animals.
3.1.8......................... Registration with and 42 CFR 71.53.
import permit from
the Centers for
Disease Control and
Prevention.
[[Page 18555]]
3.2.2......................... Document collaboration 312.52.
with accredited
microbiology labs.
3.2.3......................... Procedures to ensure 9 CFR parts 1,
the humane care of 2, and 3 and
animals. PHS Policy.\1\
3.2.4......................... Procedures consistent AAALAC
for accreditation by International
the Association for Rules of
Assessment and Accreditation
Accreditation of \2\ and NRC
Laboratory Animal Guide.\3\
Care International
(AAALAC
International) and
consistent with the
National Research
Council's (NRC) Guide.
3.2.5, 3.4, and 3.4.1......... Herd health 211.100 and
maintenance and 211.122.
surveillance to be
documented,
available, and in
accordance with
documented
procedures; record
standard veterinary
care.
3.2.6......................... Animal facility SOPs.. PHS Policy.\1\
3.3.3......................... Validate assay methods 211.160(a).
3.6.1......................... Procurement and 211.100 and
processing of 211.122.
xenografts using
documented aseptic
conditions.
3.6.2......................... Develop, implement, 211.84(d) and
and enforce SOP's for 211.122(c).
procurement and
screening processes.
3.6.4......................... Communicate to FDA 312.32(c).
animal necropsy
findings pertinent to
health of recipient.
3.7.1......................... PHS specimens to be 312.23(a)(6).
linked to health
records; provide to
FDA justification for
types of tissues,
cells, and plasma,
and quantities of
plasma and leukocytes
collected.
4.1.1......................... Surveillance of 312.23(a)(6)(iii
xenotransplant )(f) and (g),
recipient; sponsor and 312.62(b)
ensures documentation and (c).
of surveillance
program life-long
(justify >2 yrs.);
investigator case
histories (2 yrs.
after investigation
is discontinued).
4.1.2......................... Sponsor to justify 211.122.
amount and type of
reserve samples.
4.1.2.2....................... System for prompt 312.57(a).
retrieval of PHS
specimens and linkage
to medical records
(recipient and source
animal).
4.1.2.3....................... Notify FDA of a 312.32.
clinical episode
potentially
representing a
xenogeneic infection.
4.2.2.1....................... Document 312.52.
collaborations
(transfer of
obligation).
4.2.3.1....................... Develop educational 312.50.
materials (sponsor
provides
investigators with
information needed to
conduct investigation
properly).
4.3........................... Sponsor to keep 312.57 and
records of receipt, 312.62(b).
shipment, and
disposition of
investigative drug;
investigator to keep
records of case
histories.
------------------------------------------------------------------------
\1\ The ``Public Health Service Policy on Humane Care and Use of
Laboratory Animals'' (https://www.grants.nih.gov/grants/olaw/references/phspol.htm).
\2\ AAALAC International Rules of Accreditation (https://www.aaalac.org/accreditation/rules.cfm).
\3\ The NRC's ``Guide for the Care and Use of Laboratory Animals.''
Based on a review of the information collection since our last
request for OMB approval, we have made no adjustments to our burden
estimate.
Dated: April 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-08845 Filed 4-30-19; 8:45 am]
BILLING CODE 4164-01-P
