Agency Information Collection Activities; Proposed Collection; Comment Request; Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation
| Citation | 86 FR 58666 |
| Record Number | 2021-23086 |
| Published date | 22 October 2021 |
| Section | Notices |
| Court | Food And Drug Administration |
Federal Register, Volume 86 Issue 202 (Friday, October 22, 2021)
[Federal Register Volume 86, Number 202 (Friday, October 22, 2021)]
[Notices]
[Pages 58666-58670]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-23086]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0559]
Agency Information Collection Activities; Proposed Collection;
Comment Request; Public Health Service Guideline on Infectious Disease
Issues in Xenotransplantation
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
an opportunity for public comment on the proposed collection of certain
information by the Agency. Under the Paperwork Reduction Act of 1995
(PRA), Federal Agencies are required to publish notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information, and
to allow 60 days for public comment in response to this notice. This
notice solicits comments on the collection of information contained in
the Public Health Service (PHS) guideline entitled ``PHS Guideline on
Infectious Disease Issues in Xenotransplantation.''
DATES: Submit either electronic or written comments on the collection
of information by December 21, 2021.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before December 21, 2021. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of December 21, 2021. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are postmarked or the delivery
service acceptance receipt is on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2012-N-0559 for ``PHS Guideline on Infectious Disease Issues in
Xenotransplantation.'' Received comments, those filed in a timely
manner (see ADDRESSES), will be placed in the docket and, except for
those submitted as ``Confidential Submissions,'' publicly viewable at
https://www.regulations.gov or at the Dockets Management Staff between
9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management
[[Page 58667]]
Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Rachel Showalter, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 240-994-7399,
[email protected].
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA'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 on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
PHS Guideline on Infectious Disease Issues in Xenotransplantation
OMB Control Number 0910-0456--Extension
This information collection helps support implementation of the
Department of Health and Human Services' ``PHS Guideline on Infectious
Disease Issues in Xenotransplantation.'' FDA is authorized to collect
this information under sections 351 and 361 of the PHS Act (42 U.S.C.
262 and 264) and provisions of the Federal Food, Drug, and Cosmetic Act
that apply to drugs (21 U.S.C. 321 et seq.). The guideline, available
from our website at https://www.fda.gov/media/73803/download 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 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. 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
[[Page 58668]]
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.
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
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PHS guideline section Description
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3.2.7.2........................... Notify sponsor or FDA of new archive
site when the source animal
facility or sponsor ceases
operations.
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Table 2--Recordkeeping Recommendations
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PHS guideline section Description
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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.
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Table 3--Disclosure Recommendations
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PHS guideline section Description
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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.
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FDA estimates the burden for this collection of information as
follows:
Table 4--Estimated Annual Reporting Burden \1\
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Number of
PHS guideline section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
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3.2.7.2 \2\................... 1 1 1 0.50 (30 0.5
minutes).
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ FDA is using one animal facility or sponsor for estimation purposes.
[[Page 58669]]
Table 5--Estimated Annual Recordkeeping Burden \1\
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Number of Average burden
PHS guideline section Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
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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 0.50
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
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Total..................... .............. .............. .............. ................ 55.45
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\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.)
\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\
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Number of
PHS guideline section Number of disclosures Total annual Average burden Total hours
respondents per respondent disclosures per disclosure
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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 2.00
minutes).
3.5.5 \4\..................... 4 0.25 1 0.25 (15 0.25
minutes).
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Total..................... .............. .............. .............. ................ 3.08
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ FDA is using one animal facility or sponsor for estimation purposes.
\3\ FDA's records indicate that an average of one IND is 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
[[Page 58670]]
voluntary standards which reflect industry's usual and customary
business practice.
Table 7--Collection of Information Required by Current Regulations and
Standards
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21 CFR section
(unless
PHS guideline section Description otherwise
stated)
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2.2.1......................... Document offsite 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.
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 SOPs 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://olaw.nih.gov/policies-laws/phs-policy.htm).
\2\ AAALAC International Rules of Accreditation (https://www.aaalac.org/accreditation-program/rules-of-accreditation/).
\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 other than to adjust total burden hours by one hour, from 60
to 59 total burden hours, to address an inadvertent error in disclosure
burden in the previous submissions to OMB.
Dated: October 15, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-23086 Filed 10-21-21; 8:45 am]
BILLING CODE 4164-01-P
