Document ID: FDA-2012-N-0559-0005
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection;
Comment Request; Public Health Service Guideline on Infectious
Disease Issues in Xenotransplantation
Posted Date: 2015-10-05T04:00Z

[Federal Register Volume 80, Number 192 (Monday, October 5, 2015)]
[Notices]
[Pages 60153-60157]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-25155]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(the 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'' dated January 19, 2001.

DATES: Submit either electronic or written comments on the collection 
of information by December 4, 2015.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the

[[Page 60154]]

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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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 ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Public Health Service Guideline 
on Infectious Disease Issues in Xenotransplantation.'' Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), 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: (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

    The statutory authority to collect this information is provided 
under sections 351 and 361 of the 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. 301 et seq.). 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 
(section 3.2.7.1); (2) aliquots of serum samples from randomly selected 
animal and specific

[[Page 60155]]

disease investigations (section 3.4.3.1); (3) source animal biological 
specimens designated for PHS use (section 3.7.1); animal health records 
(section 3.7.2), including necropsy results (section 3.6.4); and (4) 
recipients' biological specimens (section 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 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.
    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.
------------------------------------------------------------------------

                 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 PHS 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.
------------------------------------------------------------------------

[[Page 60156]]

    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).......................             0.50
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection 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
                                        recordkeepers     recordkeeper       records       recordkeeping   hours
----------------------------------------------------------------------------------------------------------------
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  0.64
                                                                                                 minutes)
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  0.96
                                                                                                 minutes)
                                      --------------------------------------------------------------------------
    Total............................  ...............  ...............  ...............  ...............  55.45
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection information.
\2\ A one-time burden for new respondents to set up a recordkeeping system linking all relevant records. FDA is
  using one 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 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 recipients x 4 annually = 8 source animals per
  year. (See footnote 5 of table 6.)
\8\ FDA estimates ther 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Number of
                                                 Number of      disclosures    Total annual
            PHS guideline section               respondents         per         disclosures          Average burden per disclosure          Total hours
                                                                respondent
--------------------------------------------------------------------------------------------------------------------------------------------------------
3.2.7.2 \2\.................................               1               1               1  0.50 (30 minutes).........................            0.50
3.4 \3\.....................................               4            0.25               1  0.08 (5 minutes)..........................            0.08
3.5.1 \4\...................................               4            0.25               1  0.25 (15 minutes).........................            0.25
3.5.4 \5\...................................               4               1               4  0.50 (30 minutes).........................               2
3.5.5 \4\...................................               4            0.25               1  0.25 (15 minutes).........................            0.25
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................            3.08
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 1 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

[[Page 60157]]

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 collections 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 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         and 211.84.
                                    health history and
                                    lineage of source
                                    animals.
3.1.8............................  Registration with     42 CFR 71.53.
                                    and import permit
                                    from the Centers
                                    for Disease Control
                                    and Prevention.
3.2.2............................  Document              312.52.
                                    collaboration 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            AAALAC
                                    consistent for        International
                                    accreditation by      Rules of
                                    the Association for   Accreditation
                                    Assessment and        \2\ and NRC
                                    Accreditation of      Guide.\3\
                                    Laboratory Animal
                                    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        211.160(a).
                                    methods.
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     211.122(c).
                                    for 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)(ii
                                    xenotransplant        i)(f) and (g),
                                    recipient; sponsor    and 312.62(b)
                                    ensures               and (c).
                                    documentation 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'' (http://www.grants.nih.gov/grants/olaw/references/phspol.htm).
\2\ AAALAC International Rules of Accreditation (http://www.aaalac.org/accreditation/rules.cfm).
\3\ The NRC's ``Guide for the Care and Use of Laboratory Animals.''

    Dated: September 29, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-25155 Filed 10-2-15; 8:45 am]
 BILLING CODE 4164-01-P