## Compilation of OLAW Guidance and Interpretation 

# PHS Policy on Humane Care and Use of Laboratory Animals

# 

Updated April, 2006

This electronic file contains the content of notices published in the
NIH Guide for Grants and Contents and the Federal Register, former OPRR
Dear Colleague letters, and articles published by professional staff of
the NIH Office of Laboratory Animal Welfare. These documents provide
OLAW guidance and interpretation concerning the requirements of the PHS
Policy on Humane Care and Use of Laboratory Animals. This file does not
contain OLAW commentary published in the Lab Animal Protocol Review
Column or OLAW Letters to the Editor in any publications.

**Dear Colleague Letters and NIH Guide and Federal Register Notices**

**March 24, 2006 --** NIH Guide NOT-OD-06-052; Guidance on Use of
Telecommunications for IACUC Meetings under the PHS Policy on Humane
Care and Use of Laboratory Animals

**February 24, 2005** -- NIH Guide NOT-OD-05-034; Guidance on Prompt
Reporting to OLAW under the PHS Policy on Humane Care and Use of
Laboratory Animals

**July 13, 2004**- NIH Guide NOT-OD-04-052; Office of Extramural
Research Guidance Regarding Animal Welfare Documents Submitted to the
Office of Laboratory Animal Welfare

**June 6, 2003** - NIH Guide NOT-OD-03-046; Revised Guidance Regarding
IACUC Approval of Changes in Personnel Involved In Animal Activities

**August 7, 2002** - Federal Register Notice: Change in PHS Policy
Concerning Submission of IACUC Approval

**July 17, 2002** - NIH Guide NOT-OD-02-062; PHS Policy Clarification
Regarding Use of Carbon Dioxide for Euthanasia of Small Laboratory
Animals

**February 12, 2001** - NIH Guide NOT‑OD‑01‑017; Office of Extramural
Research Guidance Regarding Administrative IACUC Issues and Efforts to
Reduce Regulatory Burden

**February 3, 2000** - NIH Guide NOT-OD-00‑019; Office of Extramural
Research Guidance Concerning the Production of Monoclonal Antibodies in
Animals

**December 21, 1999** - NIH Guide NOT-OD‑00‑007; Office of Extramural
Research Guidance Regarding Reduction of Regulatory Burden in Laboratory
Animal Welfare

**November 17, 1997** - OPRR Reports Dear Colleague Letter No. 98-01;
Subject: Production of Monoclonal Antibodies Using Mouse Ascites Method

**June 2, 1997** - OPRR Reports Dear Colleague Letter No. 97-03;
Subject: Maintenance of Properly Constituted IACUCs

**March 8, 1995** - OPRR Reports Dear Colleague Letter No. 95-02;
Subject: Sources of Custom Antibody Production

**January 14, 1994** - OPRR Reports Dear Colleague Letter; Subject:
Requirements for Annual Reporting to OPRR

**January 11, 1994** - OPRR Reports Dear Colleague Letter; Subject:
Internal Distribution of Your Animal Welfare Assurance

**May 21, 1990** - OPRR Reports Dear Colleague Letter; Subject: Use of
Expedited Protocol Review Procedures by IACUCs

**Published Articles Authored by OLAW Staff Concerning PHS Policy**

**Lab Animal. 2003**;32(9):33-36. FAQs about the PHS Policy on Humane
Care and Use of Laboratory Animals.

**Lab Animal. 2002**;31(9):28-31. Correct Conduct of Full-Committee and
Designated Member Protocol Reviews.

**Lab Animal. 2002**:31(8):27-30. Disaster Recovery: "Who ya gonna
call?"

**Lab Animal. 2000**;29(5):32‑37. OLAW and APHIS: Common Areas of
Noncompliance

**Contemporary Topics. 1997**; 36(2):47‑50. FAQs about the PHS Policy on
Humane Care and Use of Laboratory Animals

**Contemporary Topics. 1996**; 35(5):53‑56. Model for Performing
Institutional Animal Care and Use Committee: Continuing Review of Animal
Research

**ILAR Journal. 1995**; 37(4):190‑192. Use of Electronic Communications
for IACUC Functions

**Lab Animal. 1995**; 24(9):24‑26. FAQs about the PHS Policy on Humane
Care and Use of Laboratory Animals

**Lab Animal. 1994**; 23(8):28‑29. Compliance at the Institutional Level

**ILAR News. 1993**; 35(3‑4):47‑49. FAQs about the PHS Policy on Humane
Care and Use of Laboratory Animals

**ILAR News. 1991**; 33(4):68‑70. The PHS Responds to Commonly Asked
Questions.

![](media/image1.wmf){width="6.55in" height="6.25e-2in"}

GUIDANCE ON USE OF TELECOMUNICATIONS FOR IACUC MEETINGS UNDER THE PHS
POLICY ON HUMANE CARE AND USE OF LABORATORY ANIMALS

NOTICE: NOT-OD-06-052

RELEASE DATE: **March 24, 2006**

Issued by: Office of Laboratory Animal Welfare (OLAW), Office of
Extramural Research (<http://grants.nih.gov/grants/olaw/olaw.htm>)

This Notice provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
concerning the use of telecommunications when a convened meeting of a
quorum of the IACUC is required under the PHS Policy on Humane Care and
Use of Laboratory Animals (PHS Policy)
(<http://grants.nih.gov/grants/olaw/references/phspol.htm>).

Background

Sections IV.C.2 and 6 of the PHS Policy require, respectively, that full
committee approval of a proposed research project or suspension of an
activity by the IACUC occur only after review of the matter at a
convened meeting of a quorum of the IACUC and with the approval or
suspension vote of a majority of the quorum present. In a 1992 article
published in the ILAR Journal (Vol.37 (4)) OPRR (now OLAW) advised that
alternate electronic methods meeting certain criteria may be considered
functionally equivalent to physically-convened meetings under
exceptional circumstances. This Notice clarifies OLAW guidance with
regard to the use of telecommunications when a convened quorum is
required.

This guidance is consistent with policies of the Office of Human
Research Protections and the Food and Drug Administration, Department of
Health and Human Services, regarding the use of telephone conference
calls for Institutional Review Board meetings under their respective
regulations for the protection of human research subjects
(<http://www.hhs.gov/ohrp/references/irbtel.pdf>).

Guidance on Use of Telecommunications for IACUC Meetings

The traditional convened meeting, physically attended by IACUC members,
provides the optimal forum in which to conduct full committee review of
proposals and consider potential suspensions. Introduction and
integration of new members to the Committee is also most effectively
accomplished during physically-convened meetings. However, OLAW
recognizes that some forms of telecommunications facilitate the conduct
of business, reduce regulatory burden, are standard practice in many
forums, and enhance flexibility without compromising the quality of
deliberation and interaction. The IACUC chairperson, as the appointed
leader of the committee, bears some responsibility for holding committee
meetings in a manner that encourages participation and facilitates
interaction among members.

Methods of telecommunications (e.g., telephone or video conferencing)
are acceptable for the conduct of official IACUC business requiring a
quorum, provided the following criteria are met:

-   All members are given notice of the meeting.

-   Documents normally provided to members during a physically-convened
    meeting are provided to all members in advance of the meeting.

-   All members have access to the documents and the technology
    necessary to fully participate.

-   A quorum of voting members is convened when required by PHS Policy.

-   The forum allows for real time verbal interaction equivalent to that
    occurring in a physically-convened meeting (i.e., members can
    actively and equally participate and there is simultaneous
    communication).

-   If a vote is called for, the vote occurs during the meeting and is
    taken in a manner that ensures an accurate count of the vote. A mail
    ballot or individual telephone polling cannot substitute for a
    convened meeting.

-   Opinions of absent members that are transmitted by mail, telephone,
    fax or e-mail may be considered by the convened IACUC members but
    may not be counted as votes or considered as part of the quorum.

-   Written minutes of the meeting are maintained in accord with the PHS
    Policy, IV.E.1.b.

The USDA Animal and Plant Health Inspection Service, Animal Care, which
is responsible for the USDA Animal Welfare Regulations that contain
identical provisions regarding convened IACUC meetings, concurs with
this Notice and will publish consistent guidance in its Research
Facility Inspection Guide.

Inquiries

For questions or further information, contact:

Carol Wigglesworth\
Acting Director\
Office of Laboratory Animal Welfare\
National Institutes of Health\
Rockledge 1, Suite 360, MSC 7982\
6705 Rockledge Drive\
Bethesda, MD 20892-7982\
Phone: 301-402-5913\
Fax: 301-402-2803\
Email: <wigglesc@od.nih.gov>

GUIDANCE ON PROMPT REPORTING TO OLAW UNDER THE PHS POLICY ON HUMANE CARE
AND USE OF LABORATORY ANIMALS

NOTICE: NOT-OD-05-034

RELEASE DATE: **February, 24, 2005**

Issued by: Office of Laboratory Animal Welfare (OLAW), Office of
Extramural Research (<http://grants.nih.gov/grants/olaw/olaw.htm>)

This Notice provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
on the prompt reporting requirements of the PHS Policy on Humane Care
and Use of Laboratory Animals (Policy)
(<http://grants.nih.gov/grants/olaw/references/phspol.htm>). This
guidance is intended to assist IACUCs and Institutional Officials in
determining what, when, and how situations should be reported under
IV.F.3 of the Policy, and to promote greater uniformity in reporting.
This Notice supersedes the January 12, 1994 Dear Colleague letter from
the former Division of Animal Welfare, Office for Protection from
Research Risks (now the Office of Laboratory Animal Welfare, or OLAW).

Background

PHS Policy, IV.F.3, requires that:

\"The IACUC, through the Institutional Official, shall promptly provide
OLAW with a full explanation of the circumstances and actions taken with
respect to:

a\) any serious or continuing noncompliance with this Policy;\
b) any serious deviation from the provisions of the Guide \[for the Care
and Use of Laboratory Animals\] ; or\
c) any suspension of an activity by the IACUC.\"

IACUC suspensions of activities are cited at IV.C.6 and 7 of the Policy,
and require a convened meeting of a quorum of the IACUC and the vote of
a majority of the quorum present. The Institutional Official must review
the reasons for suspension in consultation with the IACUC, take
appropriate corrective action and report that action with full
explanation to OLAW.

All institutions with Animal Welfare Assurances are required to comply
with the provisions of IV.F.3. The Institutional Official signing the
Assurance, in concert with the IACUC, is responsible for this reporting.

Reporting promptly to OLAW under IV.F.3 serves dual purposes. Foremost,
it ensures that institutions deliberately address and correct situations
that affect animal welfare, PHS-supported research, and compliance with
the Policy. In addition, it enables OLAW to monitor the institution\'s
animal care and use program oversight under the Policy, evaluate
allegations of noncompliance, and assess the effectiveness of PHS
policies and procedures.

The underlying foundation of the PHS Policy is one of institutional
self-evaluation, self-monitoring and self-reporting. Public Law 99-158
(<http://grants.nih.gov/grants/olaw/references/hrea1985.htm>) requires
that institutions be provided a reasonable opportunity to take
corrective action before a grant or contract is suspended or terminated,
and it is OLAW\'s role to assess whether the corrective actions reported
by institutions under IV.F.3 are adequate. OLAW will assist the
reporting institution in developing definitive corrective plans and
schedules if necessary. Compliance actions affecting an award are rare
because institutions are usually able to address incidents successfully
and take appropriate actions to prevent recurrence.

Guidance on Prompt Reporting

A comprehensive list of definitive examples of reportable situations is
impractical. Therefore, the examples below do not cover all instances
but demonstrate the threshold at which OLAW expects to receive a report.
Institutions should use rational judgment in determining what situations
meet the provisions of IV.F.3 and fall within the scope of the examples
below, and consult with OLAW if in doubt. OLAW welcomes inquiries and
discussion and will provide guidance with regard to specific situations.
Situations that meet the provisions of IV.F.3 and are identified by
external entities such as the United States Department of Agriculture or
the Association for Assessment and Accreditation of Laboratory Animal
Care International, or by individuals outside the IACUC or outside the
institution, are not exempt from reporting under IV.F.3.

Examples of reportable situations:

-   conditions that jeopardize the health or well-being of animals,
    including natural disasters, accidents, and mechanical failures,
    resulting in actual harm or death to animals;

-   conduct of animal-related activities without appropriate IACUC
    review and approval;

-   failure to adhere to IACUC-approved protocols;

-   implementation of any significant change to IACUC-approved protocols
    without prior IACUC approval as required by IV.B.7.;

-   conduct of animal-related activities beyond the expiration date
    established by the IACUC (note that a complete review under IV.C is
    required at least once every three years);

-   conduct of official IACUC business requiring a quorum (full
    Committee review of an activity in accord with IV.C.2 or suspension
    in accord with IV.C.6) in the absence of a quorum;

-   conduct of official IACUC business during a period of time that the
    Committee is improperly constituted;

-   failure to correct deficiencies identified during the semiannual
    evaluation in a timely manner;

-   chronic failure to provide space for animals in accordance with
    recommendations of the Guide unless the IACUC has approved a
    protocol-specific deviation from the Guide based on written
    scientific justification;

-   participation in animal-related activities by individuals who have
    not been determined by the IACUC to be appropriately qualified and
    trained as required by IV.C.1.f;

-   failure to monitor animals post-procedurally as necessary to ensure
    well-being (e.g., during recovery from anesthesia or during
    recuperation from invasive or debilitating procedures);

-   failure to maintain appropriate animal-related records (e.g.,
    identification, medical, husbandry);

-   failure to ensure death of animals after euthanasia procedures
    (e.g., failed euthanasia with CO 2);

-   failure of animal care and use personnel to carry out veterinary
    orders (e.g., treatments); or

-   IACUC suspension or other institutional intervention that results in
    the temporary or permanent interruption of an activity due to
    noncompliance with the Policy, Animal Welfare Act, the Guide , or
    the institution\'s Animal Welfare Assurance.

OLAW recognizes that there may be levels of morbidity and mortality in
virtually any animal-related activity, including those associated with
the care and use of animals in research, testing, and teaching that are
not the result of violations of either the Policy or the Guide . OLAW
offers the following examples of situations which may not meet the
threshold for reporting, based on consideration of the circumstances by
the IACUC.

Examples of situations not normally required to be reported:

-   death of animals that have reached the end of their natural life
    spans;

-   death or failures of neonates to thrive when husbandry and
    veterinary medical oversight of dams and litters was appropriate;

-   animal death or illness from spontaneous disease when appropriate
    quarantine, preventive medical, surveillance, diagnostic, and
    therapeutic procedures were in place and followed;

-   animal death or injuries related to manipulations that fall within
    parameters described in the IACUC-approved protocol; or

-   infrequent incidents of drowning or near-drowning of rodents in
    cages when it is determined that the cause was water valves jammed
    with bedding (frequent problems of this nature, however, must be
    reported promptly along with corrective plans and schedules).

Time Frame for Reporting

Institutions should notify OLAW of matters falling under IV.F.3
promptly, i.e., without delay. Since IV.F.3 requires a full explanation
of circumstances and actions taken and the time required to fully
investigate and devise corrective actions may be lengthy, OLAW
recommends that an authorized institutional representative provide a
preliminary report to OLAW as soon as possible and follow-up with a
thorough report once action has been taken. Preliminary reports may be
in the form of a fax, email, or phone call. Reports should be submitted
as situations occur, and not collected and submitted in groups or with
the annual report to OLAW.

Information to Be Reported

Include as many of the following items of information as possible in the
initial contact with OLAW. A follow-up report may address anything not
known at the time of the initial report and should summarize the
institution\'s corrective action. If a long term plan is necessary,
describe the plan and include a reasonable schedule. This information
will allow OLAW to assess the circumstances and actions taken to correct
and prevent recurrence of the situation.

Information to be included:

-   Animal Welfare Assurance number
    (<http://grants.nih.gov/grants/olaw/assurance/300index.htm>);

-   relevant grant or contract number(s) if the situation is related to
    an activity directly supported by PHS;

-   a full description of any potential or actual affect on
    PHS-supported activities if the situation is not directly supported
    by the PHS but is in a functional, programmatic, or physical area
    that could affect PHS-supported activities (e.g., inadequate program
    of veterinary care, training of technical/husbandry staff, or
    occupational health; inadequate sanitation due to malfunctioning
    cage washer; room temperature extremes due to HVAC failures);

-   full explanation of the situation, including what happened, when and
    where, the species of animal(s) involved, and the category of
    individuals involved (e.g., principal or co-principal investigator,
    technician, animal caretaker, student, veterinarian, etc.);

-   description of actions taken by the institution to address the
    situation; and

-   description of short- or long-term corrective plans and
    implementation schedule(s).

Preliminary and final reports should be made to:

Axel V. Wolff, M.S., D.V.M.\
Director\
Division of Compliance Oversight\
Office of Laboratory Animal Welfare\
National Institutes of Health\
Rockledge 1, Suite 360, MSC 7982\
6705 Rockledge Drive\
Bethesda, MD 20892-7982\
Phone: 301-594-2061\
FAX: 301-402-2803\
E-mail: <wolffa@od.nih.gov>

Inquiries

For questions or further information, contact:

Carol Wigglesworth\
Acting Director\
Office of Laboratory Animal Welfare\
National Institutes of Health\
Rockledge 1, Suite 360, MSC 7982\
6705 Rockledge Drive\
Bethesda, MD 20892-7982\
Phone: 301-402-5913\
FAX: 301-402-2803\
E-mail: <wigglesc@od.nih.gov>

OFFICE OF EXTRAMURAL RESEARCH NOTICE REGARDING ANIMAL WELFARE DOCUMENTS

SUBMITTED TO THE OFFICE OF LABORATORY ANIMAL WELFARE

RELEASE DATE: **July 13, 2004**

NOTICE: NOT-OD-04-052

National Institutes of Health (NIH)

This notice informs NIH awardee institutions holding Animal Welfare
Assurances in accordance with the Public Health Service Policy on Humane
Care and Use of Laboratory Animals (PHS Policy,
http://grants.nih.gov/grants/olaw/references/phspol.htm) of changes
related to two required documents. The Office of Laboratory Animal
Welfare (OLAW) will now approve Animal Welfare Assurances for periods of
up to four years. To promote consistent reporting periods OLAW now
strongly encourages awardee institutions to use the calendar year for
the reporting period of annual reports. Annual report due dates are also
now standardized.

BACKGROUND

Assurances: PHS Policy requires that approval of an assurance will be
for a specified period but no longer than five years (IV.A.). Since 1989
OLAW has approved most assurances for periods of five years. Negotiation
of a renewal assurance between OLAW and an institution may take several
months. OLAW has

traditionally administratively extended the approval period of an
assurance during the negotiation process. Unless there are indicators to
the contrary, OLAW will now approve assurances for periods of up to four
years to allow time for the review and approval of renewal assurances.
In accordance with PHS Policy, OLAW retains authority to limit the
period during which any particular Assurance is effective, or otherwise
condition, restrict, or withdraw approval.

Annual Reports: PHS Policy requires that at least once every 12 months
the Institutional Animal Care and Use Committee (IACUC), through the
Institutional Official, report certain information in writing to OLAW

(IV.F.). This information consists of any change in the institution's
program of animal care and use, in the Institutional Official and in the
IACUC membership, the dates that the IACUC conducted its semiannual

evaluations of the program and facilities, and any minority views to
reports submitted under IV.F. In most cases, institutions report on the
anniversary of the approval of their assurance. In December 1999, NIH
announced that institutions could change the date that they report in
order to synchronize the date with other annual reporting requirements,
e.g., United States Department of Agriculture and the Association for
Assessment and Accreditation of Laboratory Animal Care International
(NIH Guide Notice OD-00-007,

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-007.html).

OLAW has determined that consistent reporting periods and standardized
due dates will allow OLAW to be more responsive to the research
community and will help institutions track and comply with reporting
requirements. Although institutional flexibility to change the reporting
period (and consequently the due date) remains unaffected, OLAW strongly
encourages institutions to use the calendar year (January 1- December
31) as the reporting period. To standardize due dates, all annual
reports are due to OLAW by the last day of the month immediately
following the end of the institution's reporting period.

Guidance regarding implementation of these changes is as follows:

ANIMAL WELFARE ASSURANCE APPROVAL PERIODS

OLAW will approve assurances for periods of up to four years. Renewal
assurances must be submitted to OLAW by the expiration date of the
assurance. In most cases OLAW expects that it will administratively
extend the approval date of the assurance while the renewal is under
negotiation, up to five years as allowed by the PHS Policy. It is
incumbent upon the institution to actively participate in the
negotiation process so that the renewal assurance may be approved in a
timely manner. Institutions are reminded that without a valid
PHS-approved assurance an institution may not conduct PHS-supported
research or other activities involving live vertebrate animals.

Institutions that currently have an assurance with a five-year approval
period will be requested to submit their renewal 6-12 months prior to
the expiration date in order for the renewal to be negotiated and
approved within

the PHS Policy timeframe.

ANNUAL REPORTING PERIODS AND ANNUAL REPORT DUE DATES

OLAW strongly encourages institutions to use the calendar year (January
1 - December 31) as the reporting period. Institutions that prefer to
use a different 12-month reporting period may do so by submitting a
letter or email to OLAW by January 31, 2005, indicating the
institution's preferred reporting period. If institutions do not elect a
reporting period other than the calendar year, OLAW will consider that
the institution is defaulting to using the calendar year as its
reporting period.

To implement a calendar year reporting period, the following guidance is
provided:

o Institutions that submitted a report between January 1, 2004 and July
15, 2004 should submit their next

annual report by January 31, 2005. The reporting period, for this report
only, should be from the end of their last reporting period to December
31, 2004. For example, an institution that submitted an annual report in
April 2004 for the period of April 1, 2003 -- March 31, 2004 will report
by January 31, 2005 for the period of April 1, 2004 - December 31, 2004.

o Institutions currently scheduled to submit an annual report between
July 16, 2004 and December 31, 2004

should wait and submit their next annual report by January 31, 2005. For
these institutions, the reporting

period will be greater than 12 months for this report only. For example,
an institution scheduled to submit a

report in November 2004 for the time period of November 1, 2003 --
October 31, 2004, will report by January 31, 2005 for the period of
November 1, 2003 - December 31, 2004. Thereafter reports will be due by
January 31 of each year for the previous calendar year.

o Institutions that already use the calendar year as their reporting
period should submit their next annual report by January 31, 2005.

For institutions that elect to use reporting periods other than the
calendar year, the following guidance is provided:

o Submit an email to OLAW at assurances.olaw@od.nih.gov , or write to
the Division of Assurances, OLAW, NIH, RKL1, Suite 360, MSC 7982, 6705
Rockledge Drive, Bethesda, MD 20892-7982, by January 31, 2005, providing
the institution's preferred 12-month reporting period.

o Include the institutional assurance number in the subject line of the
email or, if submitting a letter, reference the assurance number
(numbers are available at http://grants.nih.gov/grants/olaw/
assurance/300index.htm).

o The due date for all annual reports, regardless of the reporting
period, is the last day of the month immediately following the end of
the reporting period, e.g., for the reporting period June 1 -- May 31,
the report is due June 30.

o The due date for an institution's next annual report must be within 12
months of the submission of the last report to OLAW.

INQUIRIES

For questions or further information, contact:

Office of Laboratory Animal Welfare

Office of Extramural Research

National Institutes of Health

RKL1, Suite 360, MSC 7982

6705 Rockledge Drive

Bethesda, MD 20892-7982

Telephone: 301-496-7163

Fax: 301-402-2803

Email: assurances.olaw@od.nih.gov

OFFICE OF EXTRAMURAL RESEARCH REVISED GUIDANCE REGARDING IACUC APPROVAL
OF CHANGES IN PERSONNEL INVOLVED IN ANIMAL ACTIVITIES

RELEASE DATE: **June 6, 2003**

NOTICE: NOT-OD-03-046

National Institutes of Health (NIH)

This notice amends guidance provided in 1995 to Public Health Service
(PHS) awardee institutions and Institutional Animal Care and Use
Committees (IACUCs) concerning IACUC approval of changes in personnel
involved in animal activities. This is in accord with efforts to reduce
the regulatory burden of provisions of the PHS Policy on Humane Care and
Use of Laboratory Animals (PHS Policy) and, as applicable, the USDA
animal welfare regulations (AWRs). The Office of Laboratory Animal
Welfare (OLAW), NIH, and the USDA Animal Plant Health Inspection Service
(APHIS) concur with the guidance provided in this notice.

BACKGROUND

PHS Policy (IV.B.7)
(http://grants.nih.gov/grants/olaw/references/phspol.htm) and USDA
regulations (9CFR 1, chapter 1, Part 2, 2.31(c)(7))
(http://www.nal.usda.gov/awic/legislat/awafin.htm) require the IACUC to
\"review and approve, require modifications in (to secure approval) or
withhold approval of proposed significant changes regarding the use of
animals in ongoing activities.\" In 1995, the NIH Office for Protection
from Research Risks, now OLAW, published guidance regarding examples of
\"significant change\" to approved research protocols (Lab Animal 24
(9):24-26, 1995)
(http://grants.nih.gov/grants/olaw/references/laba95.htm). This guidance
was intended to assist IACUCs in determining when a full or designated
member review process is required under the provisions of the PHS Policy
and the USDA AWRs. One of the examples of \"significant change\"
provided was \"Ychanges in personnel involved in animal procedures;Y\"

The rationale for that guidance was based on the need for the IACUC to
ensure the performance-based outcome that all personnel conducting
procedures on animals are appropriately identified, adequately trained
and qualified, and that they are enrolled in applicable occupational
health and safety programs.

IACUC APPROVAL OF CHANGES IN PERSONNEL INVOLVED IN ANIMAL ACTIVITIES

Members of the research community have pointed out circumstances under
which strict adherence to this earlier guidance may be unnecessarily
burdensome on IACUCs and research teams, without adding to the intended
protections. For example, IACUC approval of the replacement for a key
research technician or post doctoral fellow on a protocol may entail
prolonged delays in a research project, even when the individual named
as a replacement has already been fully certified by the IACUC as
qualified to perform the same procedures on a different protocol. In
addition, some institutions have applied full or designated review
requirements for adding individuals with minimal direct involvement in
animal procedures to the protocol.

OLAW, in consultation with USDA, APHIS, Animal Care, is hereby revising
the 1995 guidance on review mechanisms for personnel changes on a
protocol. IACUCs may, by institutional policy, classify certain proposed
additions and changes in personnel, other than the Principal
Investigator, as \"minor\" provided that an appropriate administrative
review mechanism is in place to ensure that all such personnel are
appropriately identified, adequately trained and qualified, enrolled in
applicable occupational health and safety programs, and meet other
criteria as required by the IACUC. The IACUC remains responsible for
confirming that all IACUC review criteria regarding personnel training
and qualifications are maintained and documented (PHS Policy IV,C,1 and
9CFR 1, chapter 1, Part 2, 2.31). Institutions will be held accountable
for ensuring the performance-based outcome that all individuals involved
in animal-related activities are competent to do so.

This guidance is intended to provide substantial reduction of burden on
IACUCs and research teams without diminishing the crucial oversight of
personnel training and qualifications.

INQUIRIES

For questions or further information, contact:

Carol Wigglesworth

Senior Policy Analyst

Office of Laboratory Animal Welfare

Office of Extramural Research

6705 Rockledge Drive

RKL 1, Suite 360, MSC 7982

Bethesda, Maryland 20892-7982

Telephone: (303) 402-5913

FAX: (301) 402-2803

<wigglesc@od.nih.gov>

**August 7, 2002** Federal Register (57 FR 51289)

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

Laboratory Animal Welfare: Change in PHS Policy on Humane Care and Use
of Laboratory Animals

AGENCY: National Institutes of Health, DHHS.

ACTION: Amended Policy Statement.

SUMMARY: The NIH is changing the PHS Policy on Humane Care and Use of
Laboratory Animals (PHS Policy) to permit institutions with PHS Animal
Welfare Assurances to submit verification of Institutional Animal Care
and Use Committee (IACUC) approval for competing applications subsequent
to peer review but prior to award.

DATES: This change in PHS Policy is effective as of September 1, 2002,
(i.e., for all applications submitted for the May-June 2003 Advisory
Council dates).

FOR FURTHER INFORMATION CONTACT: Anthony Demsey, Ph.D., Senior Advisor
for Policy, Office of Extramural Research, National Institutes of
Health, 301-496-5127, email: demseya@od.nih.gov .

SUPPLEMENTARY INFORMATION: In the March 28, 2002, [Federal]{.underline}
[Register]{.underline} (67 FR 14956), the NIH proposed to change the PHS
Policy to allow institutions to provide IACUC approval for competing
applications subsequent to peer review but prior to award. This change
would modify the PHS Policy, applicable to all PHS-conducted or
supported activities involving live, vertebrate animals, which currently
provides institutions with a PHS-approved Animal Welfare Assurance the
option of submitting verification of IACUC approval for competing
applications (1) at the time of submission, or (2) subsequent to
submission but within 60 days from the receipt date and in any case
prior to peer review. Now, with this change in the PHS Policy, IACUC
verification is no longer required to be submitted prior to NIH peer
review, but instead is simply required prior to award. This process,
already adopted as of May 1, 2000, for Institutional Review Board
approval of applications involving human subjects, is often referred to
as \"just-in-time.\" The purpose of the change is to enhance the
flexibility of institutions and reduce the burden on applicants and
IACUCs, allowing resources to be focused on substantive review of
applications likely to be funded. The change, however, permits funding
components to require verification of IACUC approval at an earlier date
if necessary.

Over 200 comments from the research community and institutional
officials were received in response to the March 28, 2002,
[Federal]{.underline} [Register]{.underline} solicitation for public
comment on the proposed change. The comments were overwhelmingly in
favor of the change; some included suggestions for NIH in its
implementation of the change. Consequently, NIH emphasizes the following
principles and expectations:

> \$ The fundamental PHS Policy requirement that no award may be made
> without an approved Assurance and without verification of IACUC
> approval remains in effect. This change only affects the timing of the
> submission of the verification of that review.
>
> \$ This change is intended to permit flexibility and discretion on the
> part of the institution. It is not a requirement that IACUC approval
> be deferred. Institutional officials retain the discretion to require
> IACUC approval prior to peer review in certain circumstances of their
> choosing if they so desire.
>
> \$ Under no circumstances may an IACUC be pressured to approve a
> protocol, or be overruled on its decision to withhold approval. NIH
> peer review groups will continue to address the adequacy of animal
> usage and protections in their review of an application, and will
> continue to raise concerns about animal welfare issues. However, in no
> way is peer review intended to supersede or serve as a replacement for
> IACUC approval. An institution that elects to use IACUC just in time
> bears the responsibility for supporting the role of the IACUC.
>
> \$ It remains incumbent upon investigators to be totally forthcoming
> and timely in conveying to their IACUCs any modifications related to
> project scope and animal usage that may result from the NIH review and
> award process. Should an institution find that one of its
> investigators disregards his/her responsibilities, the institution
> may, for example, determine that all animal protocols from that
> investigator be subject to IACUC approval before it will permit
> submission of an application from that investigator.
>
> \$ The existing PHS Policy requirement that modifications required by
> the IACUC be submitted to the NIH with the verification of IACUC
> approval remains in effect, and it remains the responsibility of
> institutions to communicate any IACUC-imposed changes to NIH staff.
>
> \$ The NIH understands its responsibility to ensure that institutions
> are given adequate notice to allow for timely IACUC review prior to
> award, and will take appropriate internal measures to fulfill its
> responsibility to establish timely feedback.

For the reasons stated above, the NIH amends the PHS Policy on Humane
Care and Use of Laboratory Animals as set forth below:

Amend the second sentence of Section IV.D.2. of the PHS Policy to delete
the words Aa time not to exceed 60 days after the receipt deadline date@
and replace them with the words Aany time prior to award unless
specifically required earlier by the funding component@ so that the
sentence states: AFor competing applications or proposals only, such
verification may be filed at any time prior to award unless specifically
required earlier by the funding component.@

The NIH Grants Policy Statement and instructions for the 398 Grant
Application Form will be modified accordingly.

Dated: 7/29/02, Elias A. Zerhouni, M.D., Director, National Institutes
or Health

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PHS POLICY ON HUMANE CARE AND USE OF LABORATORY ANIMALS CLARIFICATION
REGARDING USE OF CARBON DIOXIDE FOR EUTHANASIA OF SMALL LABORATORY
ANIMALS

Release Date: **July 17, 2002**

NOTICE: NOT‑OD‑02‑062

National Institutes of Health (NIH)

The Office of Laboratory Animal Welfare (OLAW) has determined a need to
issue Public Health Service Policy on Humane Care and Use of Laboratory
Animals (PHS Policy) guidance to Assured institutions clarifying current
requirements regarding the use of carbon dioxide (CO2) as a euthanasia
agent for small laboratory animals. Guidance regarding prompt reporting
of related serious noncompliance is included.

The Animal Care unit of the Animal and Plant Health Inspection Service,
U.S. Department of Agriculture, has reviewed and concurs with this
guidance as it relates to USDA‑covered species.

BACKGROUND

PHS Policy (http://grants.nih.gov/grants/olaw/references/phspol.htm)
requires Institutional Animal Care and Use Committees (IACUCs) to
determine that methods of euthanasia utilized in research proposals are
consistent with the Report of the American Veterinary Medical
Association Panel on Euthanasia
(http://www.avma.org/resources/euthanasia.pdf) (AVMA Panel Report),
unless a deviation is justified for scientific reasons in writing by the
investigator. IACUC approval of such deviations must be project‑specific
and include critical review of assertions of scientific necessity.
IACUCs may not otherwise disregard or issue blanket waivers of
applicable AVMA Panel Report recommendations.

Applications and proposals for awards submitted to the PHS must contain,
among other things, a description of procedures designed to assure that
discomfort and injury to animals will be limited to that which is
unavoidable in the conduct of valuable research. Reliance on this
overarching principle of minimization of pain and distress is especially
useful in resolving apparent inconsistencies and gaps in the scientific
literature and the specific guidance on CO2 use.

CLARIFICATION CONCERNING USE OF CARBON DIOXIDE

Although CO2 is generally considered an acceptable euthanasia agent for
small laboratory animals when properly administered, its acceptability
is predicated on the following:

o High concentrations of CO2 may be distressful to some species.
Accordingly, pre‑filling the chamber is recommended only under
circumstances in which such use has not been shown to cause distress.
While conclusive data are not available for all species, IACUCs and

veterinary staff should keep abreast of current peer‑reviewed scientific
literature and apply informed professional judgment to the design of
institutional policies for CO2 delivery systems and procedures, keeping
in mind the imperative to avoid or minimize discomfort, distress, and

pain when consistent with sound scientific practices.

o Death must be verified after euthanasia and prior to disposal.
Unintended recovery must be obviated by the use of appropriate CO2
concentrations and exposure times or by other means. OLAW notes that
thoracotomy after apparent death from CO2 is one way to ensure the
irreversibility of the procedure.

o Institutions must ensure that all individuals responsible for
administering CO2 euthanasia are appropriately qualified and monitored,
and that they adhere to IACUC‑approved protocols and institutional
policies.

o Chambers must not be overcrowded. In this regard, it is important to
also consider that mixing unfamiliar or incompatible animals in the same
container may be distressful.

o Compressed CO2 in cylinders is the only AVMA Panel‑recommended source
of CO2 for euthanasia purposes.

REPORTING OF NONCOMPLIANCE

Unintended recovery of animals after apparent death from CO2 (e.g., in
necropsy coolers) is a documented occurrence. Institutions are reminded
that such incidents constitute serious noncompliance with the PHS Policy
and serious deviation from the provisions of the Guide for the Care and
Use of Laboratory Animals
(http://www.nap.edu/readingroom/books/labrats/). As such, the IACUC,
through the Institutional Official, must promptly provide OLAW with a
full explanation of the circumstances and actions taken. Prompt
reporting in accordance with PHS Policy requirements (PHS Policy IV.F.3)
is an essential component of the formal relationship between OLAW and
PHS‑Assured institutions.

OLAW advises IACUCs to review their policies and practices regarding CO2
euthanasia of small laboratory animals and take appropriate action as
needed to conform to this guidance.

INQUIRIES

For questions or further information, contact:

Nelson L. Garnett, D.V.M.

Director

Office of Laboratory Animal Welfare, NIH

RKL 1, Suite 360, MSC 7982

6705 Rockledge Drive

Bethesda, MD 20892‑7982

301‑496‑7163, 301‑402‑2803 (fax)

[ng5z@nih.gov]{.underline}

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OFFICE OF EXTRAMURAL RESEARCH GUIDANCE REGARDING ADMINISTRATIVE IACUC
ISSUES AND EFFORTS TO REDUCE REGULATORY BURDEN

Release Date: **February 12, 2001**

NOTICE: NOT‑OD‑01‑017

National Institutes of Health

This notice provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
concerning the following two administrative IACUC issues: use of
alternate IACUC members and IACUC protocol and programmatic review at
collaborating institutions. It further provides an example of an
existing drug shelf life extension program that may be utilized to
extend the expiration date of certain pharmaceuticals in an animal care
and use program. A renewed Memorandum of Understanding (MOU) among USDA,
FDA and NIH is also announced.

BACKGROUND

The Office of Laboratory Animal Welfare (OLAW), NIH, and the USDA Animal
and Plant Health Inspection Service have continued to work with the NIH
Advisory Working Group on Regulatory Burden established in January,
2000, to assist and advise the NIH on issues and recommendations
presented in the report \"NIH Initiative to Reduce Regulatory Burden.\"
As a result of ongoing discussions about administrative issues dealing
with the ways that IACUCs function and

efforts by IACUCs to conduct business more efficiently, OLAW is issuing
the following guidance. The purpose of the guidance is to ensure that
IACUCs policies and procedures are in accordance with the PHS Policy on
Humane Care and Use of Laboratory Animals and, as applicable, the USDA
animal welfare regulations (AWRs). The USDA Animal and Plant Health
Inspection Service (APHIS) has reviewed and concurs with the guidance
provided in this notice.

USE OF ALTERNATE IACUC MEMBERS

Although PHS Policy and the USDA AWRs are silent on the use of alternate
IACUC members, OLAW and APHIS agree that alternates may be utilized if
the following provisions are met:

o Alternates must be appointed by the chief executive officer (CEO) of
the entity for which the committee is established, or by the official to
whom the CEO has specifically delegated, in writing, authority to
appoint IACUC members. Alternates should be listed on the IACUC rosters
submitted to OLAW with Assurances and annual reports.

o There must be a specific one‑to‑one designation of IACUC members and
alternates. This is necessary to ensure that a committee is properly
constituted, even when alternates are serving. For example, an alternate
for a non‑affiliated IACUC member would need to also meet the
non‑affiliated member requirements. Use of a pool of alternates would
not be consistent with this requirement.

o An IACUC member and his/her alternate may not contribute to a quorum
at the same time or act in an official IACUC member capacity at the same
time. An alternate may only contribute to a quorum and function as an
IACUC member if the regular member for whom they serve as alternate is
unavailable.

o Alternates should receive IACUC training or orientation similar or
identical to what is provided regular IACUC members.

o Alternate members would be expected to \"vote their conscience\" as
opposed to representing the position of the regular member for whom they
serve.

o Alternate members may be permitted to attend IACUC meetings and
participate in other IACUC activities even when the regular member is
present, at the discretion of the institution, although as stated above
they may not contribute to the formation of a quorum or vote unless the
member for whom they substitute is not available.

NO REQUIREMENT FOR DUPLICATE REVIEW

There are many circumstances that involve partnerships between
collaborating institutions or relationships between institutional animal
care programs. OLAW and APHIS agree that review of a research project or
evaluation of a program or facility by more than one recognized IACUC is
not a federal requirement.

It is imperative that institutions define their respective
responsibilities. PHS Policy requires that all awardees and performance
sites hold an approved Animal Welfare Assurance. OLAW negotiates
Interinstitutional Agreement Assurances of Compliance when an awardee
institution without an animal care and use program or IACUC will rely on
the program of an Assured institution. Assured institutions also have
the option to amend their Assurance to cover

nonassured performance sites, which effectively subjugates the
performance site to the Assured institution and makes the Assured
institution responsible for the performance site.

If both institutions have full PHS Assurances, they may exercise
discretion in determining which IACUC reviews research protocols and
under which institutional program the research will be performed. It is
recommended that if an IACUC defers protocol review to another IACUC,
then documentation of the review should be maintained by both
committees. Similarly, an IACUC

would want to know about any significant questions or issues raised
during a semiannual program inspection by another IACUC of a facility
housing a research activity for which that IACUC bears some
responsibility or exposure.

DOD SHELF LIFE EXTENSION PROGRAM (SLEP)

The Department of Defense Shelf Life Extension Program (SLEP), on the
internet at http://www.medicine.army.mil/jrcab/fda/page1.html, was
developed to defer drug replacement costs of date sensitive military
reserve stock by extending the useful life of pharmaceutical products.
The program involves the identification of candidate items by DOD
Service representatives to a Joint Readiness Clinical Advisory Board,
which submits products to the FDA.

The FDA requires submission of samples and evaluates candidate materials
using original manufacturer\'s test data to establish a protocol for
testing. The testing conducted by the FDA is comprehensive and
scientifically sound, and FDA bases expiration date extensions on
conservative estimates of the useful life of the product as
substantiated by the test results. The FDA grants the extensions as
specified by lot number, expiration date, and manufacturer that have
been stored under appropriate conditions.

Institutional animal care and use programs, although ineligible to
submit candidates for testing, may access the database of items tested
and expiration date extensions. Identified pharmaceutical products
(specified by lot number) used in animal care and use programs that have
new expiration dates need not be replaced until after the new expiration
date. Both OLAW and USDA will recognize the validity of the new
expiration dates assigned through the SLEP program.

MEMORANDUM OF UNDERSTANDING

In January 2001, USDA, FDA and NIH renewed a Memorandum of Understanding
(MOU) Concerning Laboratory Animal Welfare. Since 1995 the three
agencies have operated under an MOU that provides for enhanced
communication and allows common concerns of the agencies to be managed
in a consistent and coherent manner in spite of differing statutory or
regulatory mandates. The MOU is perhaps most effective in serving to
ensure that the differing approaches of the agencies are harmonized
without unnecessarily increasing regulatory burden. Renewal of the MOU
signals a willingness to continue the long‑standing cooperation that has
been of mutual benefit to the agencies while fostering proper animal
care and welfare. The new MOU is posted at:
http://grants.nih.gov/grants/olaw/references/finalmou.htm.

INQUIRIES

For questions or further information, contact:

Carol Wigglesworth

Senior Policy Analyst

Office of Laboratory Animal Welfare

Office of Extramural Research

6705 Rockledge Drive

RKL 1, Suite 1050, MSC 7982

Bethesda, Maryland 20892‑7982

Telephone: (301) 402‑5913

FAX: (301) 402‑2803

[carol_wigglesworth@nih.gov]{.underline}

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OFFICE OF EXTRAMURAL RESEARCH GUIDANCE CONCERNING THE PRODUCTION OF
MONOCLONAL ANTIBODIES IN ANIMALS

Release Date: **February 3, 2000**

NOTICE: OD‑00‑019

National Institutes of Health

This Notice provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
on avoiding or minimizing discomfort, distress, and pain to animals in
the production of monoclonal antibodies (mAbs), in accordance with the
PHS Policy on Humane Care and Use of Laboratory Animals.

BACKGROUND

On December 10, 1999, the NIH Director responded to a petition by the
American Anti‑Vivisection Society to prohibit the routine use of animals
in the production of mAbs. That response endorses the conclusions and
recommendations of the National Research Council (NRC) report
\"Monoclonal Antibody Production. It reiterates the applicable federal
animal welfare standards, affirms existing guidance from the Office for
Protection from Research Risks on policy implementation at the
institutional level, and lists important information resources and
NIH‑supported core facilities with tissue culture capabilities.

GUIDANCE TO AWARDEE INSTITUTIONS

Institutions should examine their current IACUC practices regarding the
review and approval of proposals to produce mAbs in animals. The IACUC
semiannual evaluation of the institutional program of animal care and
use is an appropriate mechanism for accomplishing this self‑evaluation.
Institutions should use the guidance in the following documents as the
basis for

evaluation:

o November 17, 1997 OPRR \"Dear Colleague\" letter at:
http://grants.nih.gov/grants/olaw/references/dc98‑01.htm

o the NRC Monoclonal Antibody Production Report at:

http://grants.nih.gov/grants/policy/antibodies.pdf

o the NIH Director\'s December 10, 1999 letter at:

http://grants.nih.gov/grants/olaw/references/resp121099.pdf

Institutions currently following the November 1997 OPRR guidance need
not make additional changes in order to be in compliance with the Public
Health Service Policy on Humane Care and Use of Laboratory Animals
(http://grants.nih.gov/grants/olaw/references/phspol.htm). The NRC
Report and the NIH Director\'s response should be used as additional
resources to assist IACUCs in making scientifically and ethically
informed assessments of all future proposals to use the mouse ascites
method of mAb production.

INQUIRIES

For questions or further information, contact:

Office of the Director

Office of Extramural Research

Office for Protection from Research Risks

Division of Animal Welfare

6100 Executive Blvd., Suite 3B01

Rockville, Maryland 20892‑7507

Telephone: (301) 496‑7163

FAX: (301) 402‑2803

ng5z@nih.gov

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OFFICE OF EXTRAMURAL RESEARCH GUIDANCE REGARDING REDUCTION OF REGULATORY
BURDEN IN LABORATORY ANIMAL WELFARE

Release Date: **December 21, 1999**

NOTICE: OD‑00‑007

National Institutes of Health

This notice provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
on existing ways to reduce the burden of provisions of the PHS Policy on
Humane Care and Use of Laboratory Animals (PHS Policy).

BACKGROUND

In its report on the FY 1998 budget, the House Committee on
Appropriations requested that NIH undertake an effort to streamline
Federal regulations that govern the conduct of extramural scientific
research while continuing to provide the intended protections. The
initial focus comprised five areas, one of which was animal care and
use. The report A NIH Initiative to Reduce Regulatory Burden ‑
Identification of Issues and Potential Solutions,@ available on the OER
www site at:
http://grants.nih.gov/grants/policy/regulatoryburden/index.htm was
completed in March, 1999. After public comment on the report, NIH
developed a Regulatory Burden Three‑month Plan, available on the OER www
site at:

http://grants.nih.gov/grants/policy/regulatoryburden/regburd3monthplan_09_1999.htm

The NIH Plan identified several activities that could be readily pursued
without the need for additional legislation or rulemaking. Two of the
activities called for the Division of Animal Welfare, Office for
Protection from Research Risks (OPRR), OER, to issue guidance to
institutions concerning currently available options to reduce regulatory
burden. The guidance is as follows:

SYNCHRONIZATION OF REPORTING PERIODS

The PHS Policy requires that institutions notify OPRR at least once
every 12 months of any change in the institution\'s program, any changes
in the IACUC membership, and the dates that the IACUC conducted its
semiannual evaluations of the program and facilities. Institutions that
are covered by the USDA animal welfare regulations are required to
submit APHIS Form 7023, Annual Report of Research Facility, by December
1 of every year, providing assurances concerning professional standards
governing care and consideration of alternatives, and data regarding
animals used in research. Institutions that are accredited by the
Association for the Assessment and Accreditation of Laboratory Animal
Care International (AAALAC) must submit an annual report to AAALAC
providing a program and facility update. Significant burden reduction
could result from gathering similar reporting data over the same time
period. In fact, beginning in 1998 AAALAC modified its annual reporting
requirements to allow accredited programs to employ the USDA‑specified
reporting period and animal use data.

The PHS Policy reporting requirement does not specify the time of year
that an institution must report. In most cases, by default, institutions
report to OPRR on the anniversary of the approval of the institution\'s
Animal Welfare Assurance. If institutions wish to change the date that
they report to OPRR in order to synchronize the date with other annual
reporting requirements, institutions may submit a report at any time
before the end of any given 12 month cycle, essentially resetting the
clock with regard to their annual reporting requirement under the PHS
Policy. Subsequent reports would be due 12 months later.

UTILIZATION OF AAALAC ACTIVITIES AS SEMIANNUAL PROGRAM EVALUATION

The PHS Policy requires IACUCs to review at least once every six months
the institution\'s program for humane care and use of animals, and
inspect at least once every six months all of the institution\'s animal
facilities. The IACUC is also responsible for preparing reports of the
IACUC evaluations and submitting the reports to the Institutional
Official (PHS Policy IV.B.1.‑3.). The Guide for the Care and Use of
Laboratory Animals (Guide) is to be used by the IACUC as a basis for
evaluating the program and facilities.

The PHS Policy further provides that the IACUC may, at its discretion,
determine the best means of conducting an evaluation of the
institution\'s programs and facilities. The IACUC may invite ad hoc
consultants to assist in conducing the evaluation. However, the IACUC
remains responsible for the evaluation and report. (PHS Policy, footnote
7.)

The provision to utilize ad hoc consultants may be invoked by IACUCs to
make use of either of the two AAALAC assessment programs (Program Status
Evaluation or Accreditation), or the pre‑assessment preparation
activities, to meet the requirements for an IACUC semiannual program
evaluation and subsequent report. To utilize one of these AAALAC‑
related activities as a semiannual evaluation, the IACUC must ensure
that the following provisions of the PHS Policy and USDA animal welfare
regulations, as applicable, are met:

o The IACUC report of the program review must comply with section
IV.B.3. of the PHS Policy which requires that the report contain certain
information regarding the institution\'s adherence to the Guide,
including a plan and schedule for correcting each deficiency identified
in the report.

o The report must be endorsed by the IACUC as an official IACUC report,
and submitted by the IACUC to the Institutional Official.

For institutions covered by USDA animal welfare regulations:

o the report must comply with \'2.31(c) of USDA regulations;

o at least two IACUC members must participate in the evaluation;

o no IACUC member wishing to participate in any evaluation may be
excluded;

o the report must be signed by a majority of the IACUC members; and

o the report must include any minority reviews.

The Animal Care unit of the USDA Animal and Plant Health Inspection
Service and AAALAC have reviewed and concur with the guidance provided
in this notice.

INQUIRIES

For questions or further information, contact:

Office of the Director

Office of Extramural Research

Office for Protection from Research Risks

Division of Animal Welfare

6100 Executive Blvd., Suite 3B01

Rockville, Maryland 20892‑7507

Telephone: (301) 496‑7163

FAX: (301) 402‑2803

carol_wigglesworth@nih.gov

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OPRR Reports - Number 98‑01

**November 17, 1997**

Subject: Production of Monoclonal Antibodies Using Mouse Ascites Method

Dear Colleague:

This letter provides guidance to Public Health Service (PHS) awardee
institutions and Institutional Animal Care and Use Committees (IACUCs)
on avoiding or minimizing discomfort, distress, and pain in the care and
use of animals for the production of monoclonal antibodies using mouse
ascites antibody production. The Public Health Service Act, the US
Government Principles for the Utilization and Care of Vertebrate Animals
Used in Testing, Research, and Training, the PHS Policy on Humane Care
and Use of Laboratory Animals, the Guide for the Care and Use of
Laboratory Animals, and the Animal Welfare Act provide statutory and
policy bases for the expectations in these areas (see enclosure for
citations).

There is evidence that the mouse ascites method of monoclonal antibody
production causes discomfort, distress, or pain. Practical in vitro
methods exist which can replace the ascites method in many experimental
applications without compromising the aims of the study.

Accordingly, IACUCs are expected to critically evaluate the proposed use
of the mouse ascites method. Prior to approval of proposals which
include the mouse ascites method, IACUCs must determine that (i) the
proposed use is scientifically justified, (ii) methods that avoid or
minimize discomfort, distress, and pain (including in vitro methods)
have been considered, and (iii) the latter have been found unsuitable.
Fulfillment of this three‑part IACUC responsibility, with appropriate
documentation, is considered central to an institution\'s compliance
with its Animal Welfare Assurance and the PHS Policy.

The federal mandate to avoid or minimize discomfort, pain, and distress
in experimental animals, consistent with sound scientific practices, is,
for all practical purposes, synonymous with a requirement to consider
alternative methods that reduce, refine, or replace the use of animals.
Consideration of these issues should be incorporated into IACUC review,
investigator training, research proposals, and ongoing monitoring of the
institutional animal care and use program. IACUCs, acting as agents of
institutions, are expected to implement and routinely evaluate these
aspects of the institutional animal care and use program to ensure
compliance with the PHS Policy.

Because these longstanding requirements are central to the federal
oversight of all animal‑related activities in research, testing, and
training, this guidance may also be applied more generally to other
PHS‑supported and non PHS‑supported activities involving animals.
Additional references to resources relevant to this issue are enclosed
for your information.

Thank you for your attention to these matters. As always, please feel
free to contact OPRR at 301‑496‑7163 if you have questions regarding
this correspondence.

Gary B. Ellis, Ph.D.

Director

Office for Protection from Research Risks

Nelson L. Garnett, D.V.M.

Director, Division of Animal Welfare

Office for Protection from Research Risks

Enclosures:

Statutory and Policy Bases for Consideration of Alternatives

Resources for Alternatives in Animal Care and Use

STATUTORY AND POLICY BASES FOR CONSIDERATION OF ALTERNATIVES

Health Research Extension Act of 1985, Public Law 99‑158, at Sec.
495(c):

\"The Director of NIH shall require each applicant for a grant,
contract, or cooperative agreement involving research on animals which
is administered by the National Institutes of Health \...to include in
its application\...

\"(1)\...assurances satisfactory to the Director, NIH that\...\"(B)
scientists, animal technicians, and other personnel involved with animal
care, treatment, and use\...have available to them instruction or
training in the\...concept, availability, and use of research or testing
methods that limit the use of animals or limit animal distress; and

\"(2) a statement of the reasons for the use of animals in research to
be conducted with funds provided under such grant or contract.\"

U.S. Government Principles for the Utilization and Care of Vertebrate
Animals Used in Testing,

Research, and Training, Principles III, IV, and V:

\"III. The animals selected for a procedure should be of an appropriate
species and quality and the minimum number required to obtain valid
results. Methods such as mathematical models, computer simulation, and
in vitro biological systems should be considered.

IV\. Proper use of animals, including the avoidance or minimization of
discomfort, distress, and pain when consistent with sound scientific
practices, is imperative\....

V. Procedures with animals that may cause more than momentary or slight
pain or distress should be performed with appropriate sedation,
analgesia, or anesthesia\...\"

PHS Policy on Humane Care and Use of Laboratory Animals, IV.A.1.g:

\[The Assurance shall fully describe\...\] \"a synopsis of training or
instruction in the humane practice of animal care and use, as well as
training or instruction in research or testing methods that minimize the
number of animals required to obtain valid results and minimize animal
distress, offered to scientists, animal technicians, and other personnel
involving in animal care, treatment, or use;\"

PHS Policy on Humane Care and Use of Laboratory Animals, IV.C.1.a.:

\[In order to approve proposed research\...the IACUC shall determine
that\...\] \"Procedures with animals will avoid or minimize discomfort,
distress, and pain to the animals, consistent with sound research
design.\"

Guide for the Care and Use of Laboratory Animals, 1996, National Academy
of Sciences:

\"Although scientists have also developed nonanimal models for research,
teaching, and testing\...these models often cannot completely mimic the
complex human or animal body, and continued progress in human and animal
health and well‑being requires the use of living animals. Nevertheless,
efforts to develop and use scientifically valid alternatives, adjuncts,
and refinements to animal research should continue.\" (page 1)

\"The following topics should be considered in the preparation and
review of animal care and use protocols\...Availability or
appropriateness of the use of less‑invasive procedures, other species,
isolated organ preparation, cell or tissue culture, or computer
simulation\...\" (page 10)

Animal Welfare Act, as amended by the Food Security Act of 1985, Public
Law 99‑198:

\"\[The Secretary shall promulgate\...requirements\]\...for animal care,
treatment, and practices in experimental procedures to ensure that
animal pain and distress are minimized\... that the principal
investigator considers alternatives to any procedure likely to produce
pain to or distress in an experimental animal\...\" (Section
13(a)(3)(A)&(B))

\"Each research facility shall provide for the training of scientists,
animal technicians, and other personnel\...training shall include
instruction on‑‑(1) the humane practice of animal maintenance and
experimentation; (2) research or testing methods that minimize or
eliminate the use of animals or limit animal pain or distress;\"
(Section 13(d))

CFR, Title 9, Chapter 1, Subchapter A ‑ Animal Welfare, Sec. 231(d):

\"In order to approve\...activities\...the IACUC shall determine
that\...(i) Procedures involving animals will avoid or minimize
discomfort, distress, and pain to the animals; (ii) The principal
investigator has considered alternatives to procedures that may cause
more than momentary or slight pain or distress to the animals, and has
provided a written narrative description of the methods and
sources\...used to determine that alternatives were not available.\"

CFR, Title 9, Chapter 1, Subchapter A ‑ Animal Welfare, Sec. 232(c):

\"Training and instruction of personnel must include guidance in\...(2)
The concept, availability, and use of research or testing methods that
limit the use of animals or minimize animal distress;\"

RESOURCES FOR ALTERNATIVES IN ANIMAL CARE AND USE

Adjuvants and Antibody Production, ILAR Journal, National Research
Council, Institute of Laboratory Animal Resources, Volume 37, Number 3,
pp. 92‑152, 1995.

Alternatives to the Use of Live Vertebrates in Biomedical Research and
Testing. A bibliography with abstracts prepared by the Toxicology and
Environmental Health Information Program, Specialized Information
Service, National Library of Medicine, NIH. This document is updated
quarterly. To receive the latest copy or be placed on the mailing list
call Vera Hudson at 301‑496‑1131. Also available on‑line at:
http://sis.nlm.nih.gov/altaniml.htm

Altweb is a world wide web site devoted to replacement, reduction and
refinement alternatives for research and testing, maintained by the
Johns Hopkins Center for Alternatives to Animal Testing (CAAT). The site
is: http://altweb.jhsph.edu/

Information Resources for Adjuvants and Antibody Production: Comparisons
and Alternative Technologies, Resource Series No. 3, March 1997,
available from the Animal Welfare Information Center (AWIC), NAL, USDA,
10301 Baltimore Boulevard, Beltsville, MD 20705. Also available on‑line
at: http://www.nal.usda.gov/awic/pubs/antibody.htm

NIH Plan for the Use of Animals In Research, October 1993. Copies
available from the Office of Laboratory Animal Research, OER, NIH, 9000
Rockville Pike, Building 1, Room 252, Bethesda, MD 20892.

Office for Protection from Research Risks (OPRR) laboratory animal
welfare web page available at:
http://grants1.nih.gov/grants/olaw/olaw.htm

A Report on Validation and Regulatory Acceptance of Toxicological Test
Methods, NIH Publication No.97‑3981, available from the Center for
Evaluation of Alternative Toxicological Methods, NIEHS, P.O. Box 12233,
Research Triangle Park, North Carolina 27709‑12233. Also available
on‑line at: http://ntp‑server.niehs.nih.gov/htdocs/ICCVAM/ICCVAM.html

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OPRR Reports - Number 97‑03

**June 2, 1997**

Subject: Maintenance of Properly Constituted IACUCs

Dear Colleague:

This letter provides guidance to Institutional Officials and
Institutional Animal Care and Use Committees (IACUCs) on the Public
Health Service Policy on Humane Care and Use of Laboratory Animals (PHS
Policy) regarding IACUC membership and functions.

The PHS Policy specifies that an IACUC shall consist of not less than
five members, and shall include at least: one Doctor of Veterinary
Medicine, with training or experience in laboratory animal science and
medicine, who has direct or delegated program responsibility for
activities involving animals at the institution; one practicing
scientist experienced in research involving animals; one member whose
primary concerns are in a nonscientific area; and one individual who is
not affiliated with the institution in any way other than as a member of
the IACUC, and is not a member of the immediate family of a person who
is affiliated with the institution (PHS Policy IV.A.3.b.). In addition,
institutions are reminded that in order to be consistent with the
provisions of the 1996 Guide for the Care and Use of Laboratory Animals,
nonaffiliated members should not be laboratory animal users.

For a variety of reasons, IACUCs may find their membership lacking one
or more of the requisite members specified by the PHS Policy. Although
there is no requirement that all members be present at all IACUC
meetings, the requirement that the IACUC be properly constituted in
order to conduct official business is explicit in not only the PHS
Policy and USDA Animal Welfare Regulations, but also in the
corresponding authorizing statutes. Accordingly, the validity of IACUC
actions is always predicated on the existence of a properly constituted
IACUC.

When it becomes apparent that an improperly constituted IACUC has
approved a research proposal or taken other official action, that action
is, by definition, invalid. It follows that animal‑related activities
without valid approval must be suspended until appropriate review and
approval have occurred. In addition, prompt reporting of such findings
and corrective actions to OPRR, in accordance with the PHS Policy
(IV.F.3.), is expected.

Careful attention to PHS Policy language regarding IACUC membership,
quorum, and procedures should prevent this problem from arising. Many
institutions have found that appointing more than the minimum number of
members who meet the respective PHS Policy criteria (paragraph
IV.A.3.b.) obviates problems when an unexpected vacancy occurs.

Sincerely,

Nelson L. Garnett, D.V.M.

Director, Division of Animal Welfare

Gary B. Ellis, Ph.D.

Director

Office for Protection from Research Risks

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OPRR Reports - Number 95‑02

**March 8, 1995**

Subject: Sources of Custom Antibody Production

Dear Colleague:

This letter is being forwarded to Institutional Officials and
Institutional Animal Care and Use Committee (IACUC) Chairs throughout
the country. It is provided as guidance when determining sources for the
production of antibodies in animals as part of activities supported by
the Public Health Service (PHS), either directly or as a consequence of
subgranting or subcontracting such production.

The Office for Protection from Research Risks (OPRR) is aware that some
applicant organizations are uncertain about the PHS animal welfare
requirements when animal use takes place outside the institution through
subgrants or subcontracts. A common example of this is the production of
antibodies using antigens provided by an investigator (\"custom\"
antibodies) in animals. Institutions and investigators should be aware
that if animals are utilized to produce such antibodies for use in
PHS-supported research, the organization producing those antibodies must
either have on file with OPRR an approved Animal Welfare Assurance
(Assurance) or be included as a component of the applicant
organization\'s Assurance. In addition, if species covered by the Animal
Welfare Act are utilized, the producer must be registered as a
\"Research Facility\" with the U.S. Department of Agriculture (USDA).

OPRR recognizes that many institutions have found it difficult to ensure
that investigators procuring \"custom\" antibodies do so only from
Assured sources. To facilitate and assist institutions in complying with
PHS Policy requirements, OPRR urges PHS-supported investigators and
institutions that utilize custom antibodies to follow the guidelines
presented below.

When procuring custom antibody production services from
nonninstitutional sources:

1\) Contact the proposed producer to determine its Assured status, and
if Assured, obtain the Assurance number. Alternatively, consult with
OPRR for information on the Assured status of the preferred antibody
producer. If the producer is Assured, the procurement action may proceed
without additional actions. \[NOTE: In cases where the intended producer
is known at the time a grant proposal is being submitted to the National
Institutes of Health, the producer\'s organization should be included as
a performance site on the grant application.\]

2\) If the producer is not Assured, at least two options are available:

> \(a\) Antibodies may be procured from other producers that are
> Assured; or
>
> \(b\) The producer or the applicant organization may request that OPRR
> negotiate an Assurance with the producer\'s organization. \[NOTE: If
> the producer was identified as a performance site on the grant
> application, the PHS funding component will notify OPRR of the need
> for an Assurance.\] Upon successful completion of negotiations with
> the proposed producer and approval of an Assurance, which usually can
> be accomplished expeditiously, antibodies may be procured in accord
> with 1) above.

Adherence to the above guidelines will serve several worthwhile ends:
(1) Animals involved in custom antibody production will be maintained
and used in accord with federal humane standards; (2) antibody
production will be conducted in a manner that is scientifically
reliable; and (3) compliance burdens to investigators and institutions
will be minimized.

Nelson L. Garnett, D.V.M.

Director, Division of Animal Welfare

Office for Protection from Research Risks

Gary B. Ellis, Ph.D.

Director

Office for Protection from Research Risks

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OPRR Reports - not numbered

**January 14, 1994**

Subject: Requirements for Annual Reporting to OPRR

Dear Colleague:

This letter provides Public Health Service (PHS) awardee institutions
with information and clarification in the area of animal welfare-related
annual reporting requirements.

The PHS Policy on Humane Care and Use of Laboratory Animals (Policy)
describes institutional

responsibilities with regard to required annual reports to OPRR (Section
IV.F., paragraphs 1. and 2.). Although the requirements of this section
are being fully met by a majority of awardees, there appears to be some
misunderstanding at a number of institutions regarding annual reporting
requirements.

Information from OPRR clarifying and elaborating on PHS Policy annual
reporting requirements, including a sample Annual Report format, was
provided to Institutional Officials and Chairs of Institutional Animal
Care and Use Committees in a 1990 \"Dear Colleague\" OPRR Reports,
Number 90‑02. A copy of that correspondence is attached.

Notwithstanding that 1990 communication, some institutions are
delinquent in submitting the Annual Report required by the Policy.
Further verification of our data is under way. In order to avoid
possible sanctions by this Office, please check your records to ensure
that your institution is in compliance with this PHS Policy requirement.

PLEASE NOTE THAT AN ANNUAL REPORT IS REQUIRED EVERY YEAR, INCLUDING THE
YEAR IN WHICH AN ASSURANCE RENEWAL IS APPROVED BY OPRR.

Please call OPRR at (301) 496-7163 if you have any questions regarding
the above information.

Sincerely,

Gary B. Ellis, Ph.D.

Director, Office for Protection from Research Risks

Nelson L. Garnett, D.V.M.

Director, Division of Animal Welfare, OPRR

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OPRR Reports - not numbered

**January 11, 1994**

Subject: Internal Distribution of Your Animal Welfare Assurance

Dear Colleague:

This letter is being forwarded to Institutional Officials and
Institutional Animal Care and Use Committee (IACUC) Chairs throughout
the country. Its purpose is to convey a recommendation to all
institutions conducting animal‑related activities supported by the U.S.
Public Health Service (PHS).

The Animal Welfare Assurance (Assurance) represents a legally binding
institutional commitment to the PHS, necessary for eligibility to
receive PHS support. Because of its fundamental importance to that
relationship, and because it outlines the mechanisms for implementation
of the PHS Policy on Humane Care and Use of Laboratory Animals (Policy)
at the institution, the Office for Protection from Research Risks (OPRR)
believes that the core contents of the Assurance should be generally
known by all interested parties at the institution. Although IACUC
members usually have some knowledge of the document, OPRR has
encountered situations where individual members had not actually seen
it. More frequently, many investigators and their staffs have expressed
a complete lack of awareness of the document.

When assessing compliance with the PHS Policy by awardee institutions,
e.g., during site visits, one of the principal standards against which
institutional performance is measured is the extent to which the
Assurance is adequate and accurate. In other words, does the Assurance
conform with the basic requirements of the PHS Policy and is it an
accurate description of the actual practices at the institution? These
same questions should always be addressed by the IACUC during the
semiannual review of programs and facilities. Major discrepancies
between described and actual practices have been the basis for a number
of adverse findings and actions by OPRR.

Therefore, OPRR recommends that institutions make the core contents of
their Assurance widely available within the institution for information
purposes and as an educational tool, not only for IACUC members, but
also for animal care staff, investigators, administrators, and other
interested parties.

Thank you for your attention to this important matter. Please contact
the professional staff of the Division of Animal Welfare, OPRR
(301/496‑7163), if you have any questions concerning this or any other
PHS Policy matter.

Sincerely,

Gary B. Ellis, Ph.D., Director, Office for Protection from Research
Risks

Nelson L. Garnett, D.V.M., Director, Division of Animal Welfare, OPRR

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OPRR Reports - not numbered

**May 21, 1990**

Subject: Use of Expedited Protocol Review Procedures by IACUCs

Dear Colleague:

This letter is to clarify a provision of the Public Health Service
Policy on Humane Care and Use of Laboratory Animals (PHS Policy)
regarding protocol review by Institutional Animal Care and Use
Committees (IACUCs). The Office for Protection from Research Risks
(OPRR), as a result of increased site visit activity, has identified a
number of situations in which the requirements for IACUC review of
proposed activities have been misinterpreted.

The problem involves the misuse of so‑called \"expedited\" review
procedures by IACUCs using the designated reviewer provision set forth
in Paragraph IV. C. 2. of the PHS Policy. Some institutions have
inappropriately allowed designated reviewers to grant approval and for
animal research activities to begin before all members of the IACUC have
had an opportunity to request review by the entire Committee. This
procedure is frequently referred to as \"provisional approval.\"

The process of approving research prior to providing opportunity for
each Committee member to request review by the full Committee is
contrary to the PHS Policy. OPRR considers the opportunity for any
member to call for full Committee review before approval is given and
before animal work begins to be an important safeguard of the well‑being
of animals. This PHS Policy requirement is also explicitly stated by the
U.S. Department of Agriculture in Part 2, Section 2.31(d)(2) of their
Animal Welfare Regulations.

All institutions are advised to evaluate IACUC procedures for review of
animal‑related activities for compliance with the PHS Policy and USDA
Regulations. Additionally, the institution\'s Animal Welfare Assurance
should be reviewed and, if appropriate, clarified in order to bring
institutional practices into full compliance with the PHS Policy and
USDA Regulations. If needed, amendments to Institutional Animal Welfare
Assurances should be forwarded to OPRR without delay.

Sincerely,

Charles R. McCarthy, Ph.D.

Director, Office for Protection

from Research Risks

John G. Miller, D.V.M.

Director, Division of Animal

Welfare, OPRR

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**Lab Animal.** 2003;32(9):33-36. FAQs about the PHS *Policy on Humane
Care and Use of Laboratory Animals.*

Axel Wolff, MS, DVM, Nelson Garnett, DVM, Stephen Potkay, VMD, Carol
Wigglesworth, Denis Doyle, MA, and Venita Thornton, DVM, MPH

The Office of Laboratory Animal Welfare (OLAW) of the National
Institutes of Health (NIH) develops, implements, and oversees compliance
with the US Public Health Service (PHS) *Policy on Humane Care and Use
of Laboratory Animals*^1^ (*Policy*). The PHS *Policy* and the US
Department of Agriculture's (USDA's) Animal Welfare Regulations^2^ are
the two principal federal documents that set forth requirements for
animal care and use by institutions using animals in research, testing,
and education. One of OLAW's primary functions is to assist institutions
in implementing PHS *Policy* by responding to policy-related questions.
This is accomplished by collaborating with organizations and individuals
in preparing guidance

for Institutional Animal Care and Use Committees (IACUCs) ^3--5^,
supporting the publication of monographs on various aspects of animal
care and use programs^6,7^, and publishing *Policy* interpretations in
articles^8--18^ and other formats^19--30^. OLAW also sponsors seminars
and training that specifically address current topics covering animal
care and use, and issues guidance notices in the NIH Guide for Grants
and Contracts (formerly as "Dear Colleague" letters), all of which are
found on the OLAW website (http://grants.nih.gov/

grants/olaw/olaw.htm). The following represent several additional
questions frequently asked by institutions and the OLAW responses.

1\. Does the IACUC need to require that the investigator submit the
grant application, or portions thereof, along with the IACUC animal use
protocol form for review by the IACUC? Is the IACUC

**required to compare the two for consistency?**

PHS *Policy* (IV.D.) requires the institution to verify, before award,
that the IACUC has reviewed and approved those components of grant
applications and contract proposals related to the care and use of
animals. This position is reiterated in NIH Grants Policy Statement
under Part II, Terms and Conditions. Most institutions have developed an
IACUC protocol form and require investigators to provide detailed
information about the proposed use of the animals on this form. The
signature of the authorized institutional official on any PHS
application or proposal indicates the organization's commitment to
comply with the laws, regulations, and policies to which an activity is
subject. Institutional submission of IACUC

approval, subsequent to submission of the application/proposal, must
represent approval of the information originally submitted in the
application/proposal, or include notification of any significant

changes required by the IACUC.

Although there is no explicit requirement for the IACUC to do a
side-by-side comparison of the application/proposal and the IACUC
protocol review form, it is an institutional responsibility to ensure
that the information the IACUC reviews and approves is consistent with
that contained in the application/proposal to be funded. Institutions
are free to devise a workable mechanism to accomplish this

end. One excellent way to prevent problems of inconsistencies between
the information submitted to the PHS and that on the IACUC protocol
review form is to implement a procedure for direct comparison^23^. If a
procedure of direct comparison is adopted, the individual(s) charged
with conducting the comparison should be appropriately qualified to
identify inconsistencies. Some institutions have delegated this
responsibility to a particular office or position (*e.g.*, sponsored
programs office, compliance office); others have asked Departmental
Chairs to verify consistency ^31^.

2\. Our IACUC has several categories for the approval of animal study
protocols. Which one to use depends on the kinds of issues it identifies
during review. We are sometimes unsure how best to characterize the
approval status of these projects. Can OLAW provide any advice as to
what constitutes appropriate terminology for approval of a protocol?

The PHS *Policy* recognizes only three outcomes of IACUC reviews of
proposed activities (protocols) related to animal care and use, as well
as proposals for significant changes in previously approved ongoing
activities. They are 'approve', 'withhold approval', and 'require
modifications to secure approval'. OLAW is aware that some institutions
have chosen to use different words and phrases to characterize the
latter of these outcomes, such as 'conditionally approved', 'approval
pending', 'provisionally approved', 'approved with stipulations',
'administrative approval', and 'limited approval'. We should note that
several incidents of suspensions and noncompliance are reported by
institutions to OLAW each year that are related to the conduct of
unauthorized animal studies by investigators who have misinterpreted
IACUC

responses or the approval categorization of their proposals. To avoid
such misunderstandings and the subsequent necessities to take corrective
actions and report to OLAW, this Office recommends that

IACUCs use language that is as unambiguous as possible in communicating
the results of their reviews of animal study protocols. We suggest that
institutions can do this by adhering to the language of the

*Policy* and avoiding use of the words 'approved' and 'approval' to
describe the outcome of any review that is not an unequivocal approval
and making it known that no animal work may commence without an
unequivocal approval. In addition, the IACUC approval date submitted to
PHS agencies as part of a grant

application or contract proposal must reflect the date of final
approval.

**3. Are the scientists at our institution allowed to use
non-pharmaceutical-grade chemical compounds in physiological
preparations involving laboratory animals? Please clarify whether this
is an allowable practice and whether it makes a difference if the
compounds are used in**

**survival versus nonsurvival experiments.**

The use of non-pharmaceutical-grade chemical compounds in experimental
animals under certain circumstances has been, and will continue to be, a
necessary and acceptable component of biomedical

research. OLAW and the USDA have determined that their use should be
based on (1) scientific necessity, (2) nonavailability of an acceptable
veterinary or human pharmaceutical-grade compound, and

\(3\) specific review and approval by the IACUC^32^. In preparing and
reviewing proposals to use non-pharmaceutical-grade products,
investigators and IACUCs should consider a number of related animal

welfare and scientific issues including safety, efficacy, and the
inadvertent introduction of research-complicating variables. Although
one can assume that issues such as sterility, pyrogenicity, stability,

pharmacokinetics, and quality control have been addressed during the
course of producing pharmaceutical-grade drugs, one cannot say the same
for substances produced in the research laboratory using
non-pharmaceutical-grade chemical compounds. Cost savings alone do not
adequately

justify the use of non-pharmaceutical-grade compounds in animals.
Although the potential animal welfare consequences of complications are
less evident in nonsurvival studies, the scientific issues remain the
same. The principles and need for professional judgment just outlined
still apply.

4\. Because of time constraints and the needs of our investigators, our
IACUC reviews some protocols by sending each member a copy and then
polling them to determine whether they approve. Is this procedure in
compliance with the PHS *Policy* if the IACUC members, at a subsequent
full-Committee meeting, are asked to reaffirm their votes? Is this
procedure appropriate, and if not, what must we do to correct the
situation?

No. The initial polling of members is not sufficient for approval and
initiation of work on animals. Only full Committees or designated
members can approve animal study protocols, in accordance with the PHS
*Policy* (IV.C.2). IACUC members may use electronic or other forms of
polling to call for a full-Committee review, but not to vote^12,17^. Any
animal studies undertaken on the basis of approvals resulting from such

polling would not be compliant with the PHS *Policy*. Recognizing that
urgency may sometimes be an issue in considering animal study protocols,
the PHS *Policy* allows for designated review by at least one qualified
member, appointed by the IACUC Chair, provided that all other voting
members have had an opportunity to request full review and that no
member requests a full-Committee review.

**5. Several investigators at our institution wish to use surgically
modified animals in their research but do not want to perform the
surgery in-house. We are considering the purchase of such animals and
would like to know whether the PHS *Policy* applies to customized
surgery performed at vendor facilities.**

The PHS *Policy* is applicable to all PHS-supported activities involving
animals, whether the activities are performed at a PHS agency, an
awardee institution, or other institution (PHS *Policy* at I., II.,
III., and V.B.). OLAW has provided guidance regarding animal use
(antibody production) that takes place outside the applicant/assured
institution through subgranting or subcontracting^33^. That guidance may
also serve as a template for determining whether other activities such
as customized surgery are covered by the PHS

*Policy*. In this regard, and with respect to applicability of the PHS
*Policy*, a determining issue is whether the surgery is conducted in
response to a specific custom request or whether the animals were
previously

modified and available before the request was made. If an investigator
requests that a specific custom surgical procedure or procedures be
performed on an animal for use in activities funded by the PHS, then the
organization that conducts the procedure(s) is considered a performance
site and must either have on file with OLAW an approved Animal Welfare
Assurance or be included as a component of the applicant

organization's Assurance.

6\. We are a small antibody producer using rabbits, mice, and goats, and
our work supports numerous clients, including some funded by the PHS.
When we applied for an Assurance, OLAW

**informed us that we could not approve one 'blanket protocol' to cover
all of our antibody production procedures, even though the work is
essentially always the same. Please clarify.**

Provisions of the PHS *Policy* apply to all Assured institutions
regardless of their size or mission. They include the requirement for
the IACUC to "review and approve, require modifications in (to secure

approval) or withhold approval of those components of PHS-conducted or
supported activities related to the care and use of animals," (PHS
*Policy* at IV.B.6.) on a project-specific basis. Consequently, each

proposed protocol involving antibody production as well as significant
changes (e.g., amendments) to previously approved protocols must be
submitted for IACUC review and approval, taking into account

the aims of the study and the methods proposed to avoid or minimize pain
or distress to the animals (PHS *Policy* at IV.C.1.). For example,
reviews of proposed ascites monoclonal antibody production in mice

must also critically address alternative (*in vitro*) methods as well as
pain and distress issues^6,33^. Another example would be a request for a
custom antibody against a specific protein for the purpose of vaccine

development, followed by a request for an antibody against a different
protein to be used for the same purpose. In both instances, *Policy*
would require either an amendment or a new protocol. As is the case with
any new protocol or proposed significant change to a previously approved
protocol, the PHS *Policy* allows for either full-Committee or
designated-member review. OLAW recognizes that many aspects of antibody
production are routine and recommends that institutional Standard
Operating Procedures (SOPs) be developed that describe species-specific
techniques for immunization, titer determinations, volume blood
collection, and associated procedures. One may cite IACUC-approved SOPs
in proposed project-

specific protocols or proposed amendments to avoid needless repetition.
Under these circumstances, it is possible to combine multiple projects,
or even multiple investigators, under a single protocol. However, for
PHS *Policy* purposes, IACUC approval of each project-specific protocol
submission or amendment must be readily identifiable and amenable to
tracking.

7\. May a former employee or former student of our institution be
considered for appointment to our IACUC as a nonaffiliated member?

PHS *Policy* (IV.A.3.b.4.) defines the nonaffiliated member as an
"individual who is not affiliated with the institution in any way other
than as a member of the IACUC, and is not a member of the immediate
family of a person who is affiliated with the institution," and the
USDA's Animal Welfare Regulations expect the

individual to "provide representation for the general community
interest^34^." The *Guide*^3^, which calls this person the "public
member," requires additionally that the individual not be a current
laboratory animal

user. Regarding the service of a former employee in the capacity of a
nonaffiliated member, the appointing official would have to receive
assurance that the person is not in any way conflicted or beholden to
the institution^35^. If there are no discernable ties or ongoing
affiliation with the institution,

then it would be permissible to consider appointment of the former
employee or former student to the IACUC. It is important for officials
who appoint IACUC members to determine whether real or perceived
conflicts of interest exist and make the appropriate choices to avoid
criticism about the institution's or the

Committee's integrity. Choosing an individual who is unambiguously
'nonaffiliated' is the best way to fulfill the letter and the spirit of
this provision.

8\. Our IACUC has encountered a problem with investigators who do not
submit their protocols for review in time to gain approval before the
three-year expiration date. Is it permissible to grant an administrative
extension of IACUC approval so as to avoid expiration?

No. For PHS purposes, IACUC review following the provisions at IV.C.2.
of the PHS *Policy* must be accomplished at least once every three
years^1^. The IACUC may not extend the three-year approval by any

means other than IACUC review and approval using the procedures of
IV.C.2. When IACUC approval expires, it is no longer valid. Continuation
of animal activities beyond the expiration is a serious and

reportable violation of PHS *Policy*.

**References**

1.  Public Health Service. *Policy on Humane Care and Use of Laboratory
    Animals* (US Department of Health and Human Services, Washington,
    DC, revised August, 2002).

2\. 9 CFR Chapter 1, Subchapter A---Animal Welfare, Parts 1--3.

3\. Institute of Laboratory Animal Resources, National Research Council.
*Guide for the Care and Use of Laboratory Animals* 8 (National Academy
Press, Washington, DC, 1996).

4\. ARENA/OLAW. *Institutional Animal Care and Use Committee Guidebook*,
2nd edn (2002). <http://grants.nih.gov/grants/olaw/GuideBook.pdf>.

5\. Silverman, J., Suckow, M.A. & Murthy, S. (eds.) *The IACUC Handbook*
(CRC Press, Washington, DC, 2000).

6\. Institute for Laboratory Animal Research. *Monoclonal Antibody
Production* (National Academy Press, Washington, DC, 1999).

7\. Institute for Laboratory Animal Research. *Occupational Health and
Safety in the Care and Use of Research Animals* (National Academy Press,
Washington, DC, 1997).

8\. Division of Animal Welfare, Office for Protection from Research
Risks. The PHS responds to commonly asked questions. *ILAR News* **33**,
68--70 (1991).

9\. Division of Animal Welfare, Office for Protection from Research
Risks. Frequently asked questions about the PHS Policy on Humane Care
and Use of Laboratory Animals. *ILAR News* **35**, 47--49 (1993).

10\. Wolff, A.V. & Smith, P.D. Compliance at the institutional and
programmatic level. *Lab Anim. (NY)* **23**, 28--29 (1994).

11\. Potkay, S., Garnett, N.L., Miller, J.G., Pond, C.L. & Doyle, D.J.
Frequently asked questions about the PHS Policy on Humane Care and Use
of Laboratory Animals. *Lab Anim. (NY)* **24**, 24--26 (1995).

12\. Garnett, N. & Potkay, S. Use of electronic communications for IACUC
functions. *ILAR J*. **37**, 190--192 (1995).

13\. Garnett, N.L. & Schwindaman, D. A note from the NIH and USDA. *Lab
Anim. (NY)* **25**, 22--26 (1996).

14\. Oki, G.S., Prentice, E .D., Garnett, N.L., Schwindaman, D.F., &
Wigglesworth, C.Y. Model for performing institutional animal care and
use committee; continuing review of research. *Contemp. Top. Lab. Anim.
Sci.* **35**, 33--36 (1996).

15\. Potkay, S., Garnett, N.L., Miller, J.G, Pond, C.L. & Doyle, D.J.
Frequently asked questions about the PHS Policy on Humane Care and Use
of Laboratory Animals. *Contemp. Top. Lab. Anim. Sci.* **37**, 47--50
(1997).

16\. Potkay, S. OLAW's compliance oversight: noncompliance with PHS
Policy. *Lab Anim. (NY)* **29**, 32--35 (2000).

17\. Wolff, A.V. Correct conduct of full-committee and designated-member
protocol reviews. *Lab Anim. (NY)* **31**, 28--31 (2002).

18\. Alderson, C. & Garnett, N.L. Disaster recovery: "Who ya gonna
call?" *Lab Anim. (NY)* **31**, 27--30 (2002).

19\. Garnett, N.L. & DeHaven, W.R. OPRR and USDA/Animal Care response on
applicability of the animal welfare regulations and the PHS Policy to
dead animals and shared tissues. *Lab Anim. (NY)* **26**, 21 (1997).

20\. Garnett, N.L. & DeHaven, W.R. A word from the government \[IACUC
authority\]. *Lab Anim. (NY)* **27**, 21 (1998)

21\. Garnett, N.L. & DeHaven, W.R. OPRR and USDA commentary \[protocol
review\]. *Lab Anim. (NY)* **27**, 18 (1998).

22\. Garnett, N.L. & DeHaven, W.R. The view from USDA and OPRR
\[suspension authority\]. *Lab Anim. (NY)* **27**, 17 (1998).

23\. Garnett, N.L. & DeHaven, W.R. A word from OPRR and USDA \[protocols
and grant applications\]. *Lab Anim. (NY)* **28**, 21 (1999).

24\. Garnett, N.L. A word from OPRR \[protocol extensions\]. *Lab Anim.
(NY)* **29**, 18--19 (2001).

25\. Garnett, N.L. Letter to the editor: innovative but not compliant
\[electronic protocol review\]. *Lab Anim. (NY)* **30**, 15 (2001).

26\. Taylor, K. & Wolff, A. Pass the baton \[research transfers and
pilot studies\]. *Lab Anim. (NY)* **30**, 21 (2001).

27\. Garnett, N.L. & DeHaven, W.R. A word from OLAW and APHIS \[protocol
approval\]. *Lab Anim. (NY)* **30**, 18--20 (2001).

28\. Garnett, N.L. & DeHaven, W.R. A word from OLAW and USDA \[IACUC
minutes\]. *Lab Anim. (NY*) **30**, 21--23 (2001).

29\. Garnett, N. & Gipson, C. Letter to the editor: Suggestions to bring
electronic protocol system into compliance. *Contemp. Top. Lab. Anim.
Sci.* **40**, 8 (2001).

30\. Garnett, N.L. A word from OLAW \[unapproved animal use\]. *Lab
Anim. (NY)* **31**, 19--21 (2002).

31\. Klemfuss, H. Matching protocols to grant proposals. *Lab Anim.
(NY)* **31**, 36--39 (2002).

32\. U.S. Department of Agriculture, Animal and Plant Health Inspection
Service, Animal Care, Policy 3---Veterinary Care, April 14, 1997.

33\. Garnett, N.L & Ellis, G.B Sources of custom antibody production.
OPRR Reports, Number 95-02 --- February 12, 2001.

34\. US Department of Agriculture, Animal and Plant Health Inspection
Service, Animal Care, Policy 15, IACUC Membership--- Veterinary Care,
April 14, 1997.

35\. Silverman, J., Suckow, M.A. & Murthy, S. (eds.) *The IACUC
Handbook* Section 5:25 (CRC Press, Washington, DC, 2000).

**Lab Animal. 2002**;31(9):28-31. Correct Conduct of Full-Committee and
Designated-Member Protocol Reviews

Axel Wolff, MS, DVM

Only two protocol review methods fulfill USDA and PHS
requirements---full committee and designated member. The author attempts
to lessen the confusion surrounding this issue by describing these
methods, along with examples of faulty hybrids and convenient strategies
to bring unacceptable methods into compliance.

Although the Public Health Service Policy on Humane Care and Use of
Laboratory Animals (PHS Policy)^1^ has existed since 1986 and the United
States Department of Agriculture's (USDA) Animal Welfare Act^2^
regulations governing Institutional Animal Care and Use Committees
(IACUCs) have been extant since 1989, continuing questions and
misunderstandings exist regarding the procedures used for protocol
review.

During the past several years, a significant number of Animal Welfare
Assurance submissions to the Division of Assurances, Office of
Laboratory Animal Welfare (OLAW) have proposed protocol review
procedures that are not compliant with PHS Policy. There seem to be
various reasons for this noncompliance, ranging from lack of clear
understanding of the requirements to efforts by IACUCs to improve or
streamline the processes. Previously published articles and letters to
the editor have attempted to clarify federal requirements on these
issues^3‚6^. This article will address the appropriate methods, review
some faulty "hybrids," and suggest simple steps that can be taken to
make an unacceptable method acceptable.

If an institution must comply with the Animal Welfare Act by virtue of
the animal species used or the PHS Policy because it receives support
from one of the PHS agencies (e.g., National Institutes of Health, Food
and Drug Administration, Centers for Disease Control and Prevention),
then the procedures for protocol review must be compliant with the
aforementioned documents. The review procedures are nearly identical for
both USDA and PHS and consist of only two acceptable methods, namely
full-committee review and designated-member review. The following
discussion will focus on the PHS Policy/OLAW perspective. Nothing in
this article should be interpreted to establish new PHS policy or to
reflect a change in official OLAW animal care and use guidelines. Work
with animals may not commence until appropriately approved through one
of the two recognized methods of protocol review.

Full-Committee Review

A literal reading of the PHS Policy at IV.C.2 is imperative to
understand what is expected regarding IACUC review of PHS-conducted or
-supported research projects. The Policy states that "prior to review,
each IACUC member shall be provided with a list of proposed research
projects to be reviewed. Written descriptions of research projects that
involve the care and use of animals shall be available to all IACUC
members, and any member of the IACUC may obtain, upon request, full
committee review of those research projects." The Policy explains the
actual full-committee review method as follows: "If full committee
review is requested, approval of those research projects may be granted
only after review at a convened meeting of a quorum of the IACUC and
with the approval vote of a majority of the quorum present. No member
may participate in the IACUC review or approval of a research project in
which the member has a conflicting interest (e.g., is personally
involved in the project) except to provide information requested by the
IACUC; nor may a member who has a conflicting interest contribute to the
constitution of a quorum."

Of the two methods, the concept of full-committee review is usually
easier to understand and results in fewer permutations or
"improvements." Ordinarily, the IACUC members meet in a room to review
and vote on the acceptability of research proposals (protocols)
involving research animals submitted by a principal investigator (PI). A
quorum (i.e., one person more than one half of the total number of
voting members of the IACUC) of a properly constituted IACUC (as defined
in PHS Policy IV.3.b) must be present to proceed with any official
business requiring a quorum. It is important to remember that anyone who
may have a conflict of interest cannot contribute to the quorum. The
full-committee review is to take place in real time with interaction of
the members. Previous OLAW guidance has indicated that it is acceptable
to use long-distance communication methods such as video-conferencing in
exceptional circumstances^7^.

Many IACUCs use primary reviewers during the meeting to present a
protocol to the rest of the members. A primary reviewer should not be
confused with the designated reviewer of the designated-member review
method defined later. A primary reviewer, IACUC coordinator, or other
member may be involved in some initial interaction with the PI to
prepare the protocol for review by the full committee by checking for
obvious inconsistencies, omissions, or clerical errors. Either a primary
reviewer can make the presentation, or the members can discuss the
protocol collectively with direction from the Chair.

When a vote is called for, there can be several possible outcomes.
Outright approval requires an affirmative vote by a majority of the
convened quorum present. In the event that substantive questions prevent
final approval, the committee can wait until the next meeting for
revisions to be reviewed by the full committee. Alternatively, the
committee can decide to handle the resubmission by the designated-member
review process, with appropriate notation in the minutes. Although PHS
Policy does not recognize protocols in this status, IACUCs often refer
to them as "conditionally" or "provisionally" approved. However, this
designation does not allow animal work to begin, nor can the date of the
meeting serve as an IACUC approval date for use on a grant application.

The committee members can also vote to withhold approval if they feel
that the requirements of PHS Policy or other stipulations have not been
satisfied. Other officials at the institution cannot overturn this
decision. The PI must receive written notification, including the reason
for this decision, and must have an opportunity to respond in person or
in writing.

IACUCs may invite consultants to assist in the review of complex
protocols, but consultants cannot vote unless they are officially
appointed voting members on the committee.

Designated-Member Review

The second accepted method of protocol review is known as
"designated-member review." The actual Policy description of this method
is as follows: "If full committee review is not requested, at least one
member of the IACUC, designated by the Chairperson and qualified to
conduct the review, shall review those research projects and have the
authority to approve, require modifications in (to secure approval) or
request full committee review of those research projects."

This method is equally acceptable for use by IACUCs when conducting
protocol review, but it must proceed as outlined in the PHS Policy.
Using this method, all IACUC members receive a list of proposed research
projects and access to the necessary information on the protocol to be
reviewed. If any member feels that this protocol should go before a full
committee, then its review must be deferred to the next full IACUC
meeting. Any member can make the decision to send the protocol to
full-committee review at any time during the time period designated for
providing this opportunity. It is useful for IACUCs to allow a
predetermined time period during which members may indicate which method
of review is preferred. If no member calls for a full-committee review,
then the Chair can refer the protocol in question to a designated
reviewer. The Chair may select one or more members, qualified to review
this specific protocol, who will act on behalf of the entire IACUC to
approve the protocol, request additional information from the PI to
approve it, or refer it for full review. The designated reviewer does
not have the power to withhold approval, however, but must in such cases
refer the protocol for full-committee review.

The designated-reviewer approval has equal validity to full-committee
review approval and does not require subsequent reapproval or
notification by a convened meeting. It is always possible for the IACUC
to discuss protocols approved by either method in future meetings as a
form of continuing review or in response to animal welfare concerns.

Common Errors

In efforts to facilitate the designated-member review procedure, many
IACUCs have suggested incorrect variations. Even if these methods result
in faster review or other perceived benefits, one must remain aware that
the two recognized methods are the only presently acceptable ones as a
condition of PHS support. No changes in the current IACUC review
requirements are permissible without a formal change in the PHS Policy.
Along with the following examples of faulty use of designated-member
review, I offer suggestions for making the review compliant.

Unacceptable Method 1

Each IACUC member receives a copy of the protocol (paper or electronic),
decides on approval, and sends a "vote" back to the Chair. The Chair
notes that a majority approves, concurs, and signs the protocol as
approved. This is a hybrid of both recognized methods that does not meet
the requirements of either.

Correction: The feedback from the members should only concern their
concurrence with the use of a designated-member review or a call for
full-committee review. If there is no call for full-committee review, it
is still acceptable for members to share comments with a designated
reviewer, who can use this information in conducting the
designated-member review as described earlier.

Unacceptable Method 2

The IACUC members receive a copy of the protocol. As soon as a quorum of
the members reply that they do not request full-committee review, and
before the end of the predetermined time period provided to all members
to request full-committee review, the Chair initiates designated-member
review.

Correction: In this case, not all members were given sufficient time to
reply. The committee should determine a definite time frame during which
members must submit replies. IACUCs may consider the lack of a reply as
equivalent to declining to call for full review, but only after the full
time period has elapsed. If all voting members reply before the end of
the predetermined time period and there are no requests for
full-committee review, the Chair is at liberty to initiate
designated-member review.

Unacceptable Method 3

The IACUC members receive a copy of the protocol, no one responds, and
hearing no negative comments or call for full review, the Chair
automatically considers the protocol approved.

Correction: This does not meet the requirements of designated-member
review because no one was appointed designated reviewer. It also appears
that no review was conducted; this is a violation of PHS Policy. The
absence of a request for full review must lead to the appointment of a
designated reviewer(s), and the correct procedure followed.

Unacceptable Method 4

The IACUC members indicate that a protocol can be handled by
designated-member review and the Chair selects three reviewers. Two
reviewers vote to approve and one votes to withhold. The Chair considers
the protocol approved.

Correction: Under designated-member review, all participants must either
approve or require (the same) modifications for approval; failing this,
they must submit the protocol for full-committee review. In this case,
the reviewers will not actually be voting with a majority-rules outcome.

Unacceptable Method 5

The designated reviewer considers a protocol to be marginally acceptable
and assigns a "provisional approval" but thinks it would be best for a
final decision to come from a full-committee review at the next meeting.
The PI starts the work with the possibility of having to stop once the
full committee meets.

Correction: Again, this situation constitutes an unacceptable hybrid.
The designated reviewer should fully approve a protocol, allowing the
work to start without additional review needed, or require modification,
or submit the protocol for full-committee review. Designated members
should be qualified to conduct the specific review to allow a competent
final decision.

Unacceptable Method 6

The IACUC develops a flowsheet whereby certain studies (e.g., primate,
dog, survival surgery) automatically must have full-committee review
whereas other studies (e.g., antibody production, rodent behavior) are
directed to a standing committee of designated reviewers.

Correction: The routing to a full committee is acceptable, as is the
default submission to the designated reviewers, provided the remainder
of the committee has the opportunity to call for full-committee review.
Only after all members have, as a minimum, received a list of proposed
research projects, had written descriptions of those projects available
to them, and decided that full-committee review is not necessary, can
the designated reviewers handle it.

Unacceptable Method 7

The IACUC Chair prereviews submitted studies, decides that certain
benign proposals would result in a unanimous decision by the members in
favor of designated-member review, and therefore chooses to be the
reviewer and approves the study, informing the committee at the next
meeting.

Correction: Here the Chair has bypassed the committee members, who do
not have the opportunity to call for full review. Only after all have
had the opportunity and no one expresses the need for full review can
the Chair become the designated reviewer and approve on behalf of the
entire IACUC.

Potentially Acceptable Method 8

All members receive a copy of the protocol and all are designated
reviewers. This arrangement can work in theory but may be difficult to
accomplish logistically. In this instance all reviewers need to examine
each subsequent revision. Every IACUC member must approve, rather than
just the majority of the members. Abstention is not permissible because
this approach does not operate on a majority-rule basis.

Conclusions

In all of the cases just presented, the critical issue in bringing them
into compliance is the initial inclusion of all members in the
opportunity to examine the protocol and subsequently to decide to forgo
a full review in favor of the designated-member review. Once members
have chosen designated-member review, then the reviewer(s) assumes the
responsibility for the full committee in granting unanimous approval,
requiring modification, or sending the protocol for full review.

Everything discussed here regarding the recognized methods of protocol
review is equally applicable to the review of proposed significant
changes to ongoing, approved protocols and to the PHS triennial
continuing-review requirement. The IACUC should formulate, in advance, a
list of what changes it would consider significant (see ref. 8 for
examples) and apply exactly the same methodology for review. All members
must have a chance to examine proposed significant changes, either in
full-committee review or in determining whether to use the
designated-member review method. As in protocol review, any member can
request that the change be presented to the full committee and have this
request honored**.**

When an Assurance is submitted to OLAW, it is important to outline
clearly and accurately the methods that the IACUC used under discussion
for reviewing protocols and significant changes. The description should
clearly explain the method for conducting the procedures at that
institution, so that OLAW can assess whether the method is compliant.
Once an Assurance is approved, the described method is considered
acceptable for review of protocols and significant changes at that
institution. The annual report to OLAW should include any changes to the
institution's approved protocol review process. OLAW welcomes questions
on this subject; it is the office's mission to ensure that Assured
institutions remain compliant.

Received 5/29/02; accepted 6/24/02.

References

1\. Public Health Service. Policy on Humane Care and Use of Laboratory
Animals (US Department of Health and Human Services, Washington, DC,
1986; reprinted 2000).

2\. Code of Federal Regulations. Title 9, Chapter 1, Subchapter
A---Animal Welfare, Parts 1--3.

3\. Garnett, N. & Gipson, C. Suggestions to bring electronic protocol
system into compliance (letter to editor). Contemp. Top. Lab Anim. Sci.
40, 8 (2001).

4\. Garnett, N. & DeHaven, W.R. Innovative, but not compliant (letter to
editor). Lab Anim. (NY) 30, 15 (2001).

5\. Garnett, N. & DeHaven, W.R. OPRR and USDA Commentary. Lab Anim. (NY)
27, 18 (1998).

6\. Oki, G.S.F., Prentice, E.D, Garnett, N.L, Schwindaman, D.F. &
Wigglesworth, C.Y. Model for performing Institutional Animal Care and
Use Committee: continuing review of animal research. Contemp. Top. Lab
Anim. Sci. 35, 53--56 (1996).

7\. Garnett, N. & Potkay, S. Use of electronic communications for IACUC
functions. ILAR J. 37, 190--192 (1995).

8\. Potkay, S., Garnett, N.L., Miller, J.G., Pond, C.L. & Doyle, D.J.
Frequently asked questions about the Public Health Service Policy on
Humane Care and Use of Laboratory Animals. Lab Anim. (NY) 24, 24--26
(1995).

Last Updated October 10, 2002.

**Lab Animal. 2002**;31(8):27-30. Disaster Recovery: "Who ya gonna
call?"

CAROL ALDERSON AND NELSON L. GARNETT, DVM

\[Alderson is Assistant Grants Policy Officer, Office of Policy for
Extramural Research Administration, Office of Extramural Research,
National Institutes of Health, Bethesda, MD; Garnett is Director, Office
of Laboratory Animal Welfare, Office of Extramural Research, National
Institutes of Health, Bethesda, MD. Please send reprint requests to
Garnett at OLAW, NIH, RKL1, Suite 360, MSC 7982, 6705 Rockledge Dr.,
Bethesda, MD 20892, or email: <ng5z@nih.gov>.\]

When dealing with recovery from a disaster, NIH-funded animal research
institutions have certain

responsibilities to OLAW and OPERA. The authors outline these
responsibilities and identify areas in which these offices can aid the
affected institution in the recovery effort.

In the past year, National Institutes of Health (NIH) grantees have
confronted both a tropical storm and a terrorist attack. In Houston, TX,
investigators from the University of Texas Health Science Center at
Houston and Baylor College of Medicine suffered enormous research
losses---including more than 35,000 research animals and thousands of
tumor samples from a 20-year breast cancer project---as a result of
flooding caused by Tropical Storm Allison. In New York City, the
National Development and Research Institute, Inc. (NDRI), a nonprofit
research and educational organization that was located in Tower 2 of the
World Trade Center, lost years' worth of data stored on computers as a
consequence of the September 11 terrorist attacks. Out of these tragic
and unforeseen events, NIH extramural staff members have learned
valuable lessons regarding methods by which research institutions could
prepare for disasters and possibly thus lessen their impact.

When disaster---whether natural or otherwise---strikes an animal
research facility, the highest priority must be saving human and animal
lives. Nevertheless, once the acute stage of the disaster has ended,
institutions receiving support from the NIH, and, therefore subject to
NIH grants policy and the *Public Health Service Policy on Humane Care
and Use of Laboratory Animals*^1^ (PHS *Policy*), have certain
responsibilities to two related components of the NIH, Office of
Extramural Research (NIH/OER). These are the Office of Laboratory Animal
Welfare (OLAW) and the Office of Policy for Extramural Research
Administration (OPERA).

Drawing mainly on experiences related to the aftermath of Tropical Storm
Allison, we will address institutional responsibilities to OLAW and
OPERA, as well as provide insights regarding the help that these two
offices can provide to affected institutions. The OLAW section addresses
the issues of communicating information important to the oversight of
laboratory animal welfare such as reporting the extent of losses and
damage to the program of animal care and use and the institution's plan
for recovery to its former fully compliant condition. The OPERA section
deals with those NIH grants policy issues relevant to disaster recovery
and serves to assist institutions with the rapid return to productivity
in their NIH-supported biomedical research programs. We will not attempt
to cover in detail the preparedness aspect of the overall disaster plan.

OLAW

# *Federal Regulations and Policy*

Amazingly, there is nothing in the PHS *Policy* and only one paragraph
in the *Guide for the Care and Use of Laboratory Animals* ^2^ (*Guide*)
that even addresses disasters. The *Guide* recommends "a disaster plan,
as part of an overall safety plan, that takes into account both
personnel and animals," and states that the veterinarian or manager
should be on the safety committee and an "official responder," but
provides no additional guidance.

In May 1997, OLAW, Case Western Reserve University, and the Ohio
Scientific Education and Research Association (OSERA) cosponsored a
meeting in Cleveland entitled, "Development of Institutional Disaster
Plans." Based on this meeting, many institutions started thinking about
being proactive on the subject of disaster planning and response. In his
account of experiences during Hurricane Hugo at the Medical University
of South Carolina in Charleston, Michael Swindle, DVM, Professor and
Chairman in the Department of Comparative Medicine at the Medical
University of South Carolina, stated:

"Experience with hurricanes, which are the only disaster for which you
have significant warning, has taught us that disasters do not follow
SOPs \[standard operating procedures\]. During the emergency the outcome
will be determined by the ability of the leadership on site at the time
of the disaster to respond and make decisions spontaneously. Disaster
relief agencies will not be available during the disaster and its
immediate aftermath. SOPs are more useful for the long-term recovery
period. Their greatest usefulness is that they indicate that you have
thought about disasters and not as a document that can be relied upon to
be followed faithfully during a disaster^3^."

More information is available in a chapter on emergency preparedness in
the second edition of the ARENA/OLAW *IACUC Guidebook*^4^. In addition,
plans are underway at OLAW to support the development of additional
resources for the laboratory animal community addressing this topic.

## *When and Why to Contact OLAW*

PHS *Policy* (IV.F.3) describes three rather specific circumstances that
require a prompt report to OLAW: "The IACUC, through the Institutional
Official, shall promptly provide OLAW with a full explanation of the
circumstances and actions taken with respect to: a. any serious or
continuing noncompliance with this Policy; b. any serious deviation from
the provisions of the *Guide*; or c. any suspension of an activity by
the IACUC^1^."

It should be apparent to most that there will likely be significant
deficiencies and serious deviations from the *Guide* after a natural
disaster. OLAW has published guidance on what constitutes "significant"
and "serious" in the two slightly different contexts of semiannual
reporting and prompt reporting ^5^. "The term 'significant deficiency,'
used in the PHS *Policy* and the USDA Animal Welfare Regulations, refers
to any facility or program deficiency that is or may be a threat to the
health or safety of animals. Program or facility deficiencies, including
accidents and natural disasters, which cause injury, death, or severe
distress to animals, are, by definition, 'significant'. Although it is
not possible to provide an exhaustive listing of examples, some
illustrations of significant facility deficiencies include failures in
heating, ventilating, and air conditioning systems and their associated
electrical systems; inoperative watering systems; and general power
failures of sufficient duration to affect critical areas such as
isolators, barriers, surgical suites, and intensive care units.... When
deficiencies involve serious or continuing noncompliance with the PHS
*Policy*, serious deviations from the \[*Guide*\], or the IACUC
suspension of any activity, the circumstances and actions taken must be
reported promptly to OPRR \[now OLAW\] as required in section
IV.F.3.a--c. of the PHS *Policy*. Reporting of such deficiencies should
not be deferred for inclusion in the institutional annual report^5^."

Answers to the question of when to report will vary depending on the
circumstances, but OLAW would like to hear from institutions as soon as
possible after the acute crisis phase, and before the inevitable
inquiries start coming in from other sources. One of those other sources
may be the NIH director asking OLAW about how all those NIH-funded
animals at (insert name of your institution) are doing. Animal rights
activists may take such an opportunity to initiate complaints, as we saw
immediately after Tropical Storm Allison. It is extremely important for
us to be able to reassure ourselves and other interested parties that we
know what is happening and that everything possible is being done to
take care of the animals. The most common way for you to report promptly
to OLAW is by telephone; however, fax, email, and other forms of
communication all qualify as a "prompt report." Other reasons to call,
aside from being a requirement, include the possibility that we can be
of assistance; we may have access to resources or contacts that can help
your institution deal with the problems.

### The Long Road to Recovery

As institutions begin to emerge from the acute crisis phase, there will
undoubtedly be actions that take immediate priority because of the need
to mitigate or prevent further losses. Such priorities include
relocating animals, saving frozen tissues and samples, and recovering
essential computer files and other records. Although this article does
not attempt to elaborate on the disaster preparation phase, an
institution's ability to minimize secondary losses will depend
substantially on the effectiveness of that preparation. For example,
accurate risk assessment and appropriate prevention strategies may keep
animals and other critical assets out of harm's way for certain types of
emergencies.

Next comes the difficult task of rebuilding. At this stage, OLAW really
does need to know more about the institution's "reasonable and specific
plan and schedule^1^" to get back to a fully compliant state. PHS
*Policy* does allow for certain deficiencies to exist at Assured
institutions provided that they have been identified, along with
credible correction plans. These plans are often negotiated with OLAW
through the prompt and annual reporting processes and become an integral
part of the institutional Assurance. Longer-term disaster recovery
efforts may be viewed in the same context as correction of other more
routine facility or program deficiencies. Though often on a different
scale of importance, the semiannual facility inspection and program
review process provides a good model for addressing the disaster
recovery phase, which should include establishing specific target dates
for correction and should monitor progress on an ongoing basis until
completion.

Sometimes a recovery plan requires the development of interim plans.
While some damaged facilities may not be suitable for their original
design function, they may still be satisfactory to support a more
limited role. For example, a damaged building HVAC system may not
provide adequate ventilation for animal housing at full capacity, yet it
may be acceptable for reduced population loads or lower levels of
isolation or containment.

# *Get By with a Little Help from your Friends*

Another interim plan might involve seeking assistance from resources
outside the institution. For example, in the aftermath of Tropical Storm
Allison, we witnessed excellent cooperative arrangements between two
neighboring institutions. The University of Texas M.D. Anderson Cancer
Center agreed to share some of its valuable animal housing, research
space, and equipment with the University of Texas Health Sciences Center
at Houston to allow vital research to continue. OLAW was pleased to
facilitate that arrangement by approving the interinstitutional
agreements and appropriate modifications to the respective Assurances.

OPERA

# *Know Who Is in Charge*

It may be helpful to look at NIH grantee responsibilities before the
declaration of a disaster. These responsibilities begin when an
organization submits a grant application to the NIH. The face page of
the Public Health Service Grant (PHS 398) application includes a
signature block for the authorized organizational official. This is the
official that your organization has authorized to act for the applicant,
and to assume the obligations imposed by the encompassing federal
requirements that apply to grant applications and grant awards. The
official's signature on the grant application further certifies that the
organization will be accountable for both the appropriate use of funds
and the grant-supported activities described in the application. In
signing a grant application, this official certifies that your
organization will comply with all applicable assurances and
certifications referenced in your application.

#### 

#### Protect Your Research Assets 

If your grant application is successful and the NIH issues your
institution an award, what are your responsibilities associated with
receiving NIH research funds? OMB Circular A-110 (ref. 6) and

Department of Health and Human Services (HHS) regulations at 45 CFR 74
(ref. 7) require recipients of NIH grants and cooperative agreements to,
at a minimum, provide insurance coverage for equipment acquired with
federal funds equivalent to that provided for equipment owned by the
recipient. Also, A-110 and 45 CFR 74 require effective control over and
accountability for all funds, property, and other assets, to provide
adequate security for all such assets and to assure that they are used
solely for authorized purposes. While you may read these requirements as
typically applying to financial management systems and procedures, these
same safeguards apply to the additional systems that support ongoing
research.

What are the best measures for safeguarding your institution's research
assets? An examination of some basic institutional systems would be
instructive. For example, many institutions locate emergency power
generators in the basement, which is the first area to suffer damages in
a flood. A sensible safeguard would be to have an emergency generator
located somewhere other than the basement of a building, and to assure
that all generators receive regular fueling. Do you know what is in your
research freezer? Prepare an inventory of the contents of your freezers
and valuable research supplies, maintain the inventory regularly, and
store a copy of the inventory in an alternate location. Another
vulnerable area consists of research data that are stored on one
computer without appropriate backup. There have been unfortunate
incidents in which years' worth of research data were stored on a single
computer without backup, and then lost in a disaster. Data should be
backed up to a secure network or removable media such as zip disks,
CD-ROMs, or an external hard drive, and stored in a different location.
And remember that both computers and backup systems must always meet the
appropriate level of security that is

required for the data involved.

While, fortunately, NDRI did not lose staff in the attack of September
11, some investigators lost years' worth of data that were stored on
their computers. However, one investigator had a method to protect her
data. She backed up her computer and ran a virus scan as a part of her
daily routine. She then transported her backup media or "shuttle disk"
to her home, where she transferred the information to her home computer.
And once a week she backed up her home computer to a CD that she keeps
in a locker at her gymnasium. She had a plan to protect the contents of
her computer and, before last September, her routine may have appeared
excessive. Yet her plan undoubtedly served her well in this situation.

Take an inventory and determine what components of your research
projects are irreplaceable. Next, determine the means by which you can
protect them. Involve your institutional official. Learn how your
institution's facilities and information technology (IT) officials have
prepared for a disaster. With this information, you can prepare a
disaster plan for your research.

# *There's a Problem---Now What?*

The process of assessing research losses can begin only after the event
has passed and your safety can be assured. Once your organization has
begun to estimate losses, it is very important that you contact the
appropriate scientific program officials and grants management
specialists at NIH, usually by an email or a fax message, to notify them
of potential delays, possible research setbacks, or relocations of
research. We suggest also sending a copy of this notification to your
organizational official.

The unforeseen nature of these disasters inevitably leads to a
significant administrative burden to account for and document the
event's impact. Your organization will be expected to meet the ongoing
responsibilities that are associated with receiving NIH awards as well
as completing the necessary work to document the losses associated with
the event. Institutions that were severely affected by Tropical Storm
Allison retained consultants to advise and assist them with the myriad
of issues.

### What Can NIH Do?

The NIH realizes that these events may cause problems for investigators
who are planning to submit competing and noncompeting grant applications
for upcoming receipt dates. The NIH will typically announce in the NIH
"Guide for Grants and Contracts" (NIH Guide) that late applications from
affected institutions will be accepted by NIH ^8^. The NIH Guide is
available directly from the Office of Extramural Research (OER) website
(<http://grants.nih.gov/grants/oer.htm>.

While the NIH does not have legislative authority to provide disaster
relief for biomedical research organizations, it can support the ongoing
projects that were affected by the event. The NIH can consider requests
for administrative supplements for these projects. These requests can
include extensions in time that involve personnel costs, as well as
replacement of equipment, supplies, and unique resources damaged or lost
as a result of the storm. The application should state that the
requested support does not represent a duplication of benefits, for
example, from insurance.

The NIH has worked closely with senior staff from the Federal Emergency
Management Agency (FEMA, [http://www.fema.gov](http://www.fema.gov/)) to
assist with the recovery efforts of research institutions affected by
Tropical Storm Allison. FEMA works directly with the states to help plan
for disasters, develop mitigation programs, and meet needs when major
disasters occur. To make sure that institutions affected by Tropical
Storm Allison would obtain maximum compensation for storm-related
losses, the NIH and FEMA determined which costs would be allowable under
their respective programs and then published this information in the NIH
Guide^9^.

If an institution has a need for physical infrastructure after a
disaster, then the National Center for Research Resources (NCRR), one of
the NIH's 27 institutes and centers, and the leading federal sponsor of
shared research resources that support scientific research, can help.
The NCRR's Research Facilities Improvement Program (RFIP) provides
grants to public and nonprofit private biomedical institutions to
expand, remodel, and renovate or alter existing research facilities or
construct new research facilities. Improvements under this program must
support basic and clinical biomedical or behavioral research as well as
research training (*see* http://www.ncrr.nih.gov/resinfra/riresfac.htm).
The NCRR also supports the Animal Facilities Improvement Program (AFIP).
The AFIP grants provide for the upgrading of animal facilities that
support biomedical and behavioral research funded by US PHS agencies. In
addition to upgrading the facilities, these grants assist institutions
to comply with the Animal Welfare Act, administered by the US Department
of Agriculture, as well as the Department of Health and Human Services
(HHS) policies related to the care and use of laboratory animals (*see*
<http://www.ncrr.nih.gov/resinfra/riafip.htm>. Please note that
eligibility for these programs is not limited to institutions that have
experienced a disaster.

##### Conclusion

Both authors wish to express their sincere appreciation and admiration
for the many individuals with whom they have interacted during and after
the events mentioned in this article. We recognize that, without the
dedication and sometimes heroic efforts of the many good people
involved, no recovery effort could have been successful.

Received 5/3/02; accepted 5/15/02*.*

###### References

1\. Public Health Service. *Public Health Service Policy on Humane Care
and Use of Laboratory Animals* (US DHHS, Washington, DC, 1986).
<http://grants1.nih.gov/grants/olaw/references/phspol.htm>.

2\. Institute of Laboratory Animal Resources, National Research Council.
*Guide for the Care and Use of Laboratory Animals* (National Academy
Press, Washington, DC, 1996).
http://www.nap.edu/readingroom/books/labrats/.

3\. Swindle, M.M., Taylor, L.L., Reed, C. & Wagner, J.L. Hurricanes and
animal care programs. *Lab Anim. (NY)* **22,** 25--31 (1993).

4\. ARENA/OLAW. *Institutional Animal Care and Use Committee Guidebook*
2nd edn (2002). http://grants1.nih.gov/grants/olaw/GuideBook.pdf.

5\. Potkay, S., Garnett, N., Miller, J.G., Pond, C.L. & Doyle, D.J.
Frequently asked questions about the *Public Health Service Policy on
Humane Care and Use of Laboratory Animals*. *Contemp. Top. Lab. Anim.
Sci*. **36,** 47--50 (1997).
http://grants1.nih.gov/grants/olaw/references/faq_labanimals1997.htm#1.

6\. Office of Management and Budget. Circular A-110 (Revised 11/19/93,
as further amended 9/30/99).
http://www.whitehouse.gov/omb/circulars/a110/a110.html.

7\. 45 CFR. Part 74. Department of Health and Human Services. Uniform
administrative

requirements for awards and subawards to institutions of higher
education, hospitals, other nonprofit organizations, and commercial
organizations; and certain grants and agreements with states, local
governments and Indian tribal governments.
http://www.access.gpo.gov/nara/cfr/waisidx_00/45cfr74_00.html.

8\. National Institutes of Health. Delays in grant application
submissions due to Tropical Storm Allison.

NOT-OD-01-041 (21 June 2001).
http://grants2.nih.gov/grants/guide/noticefiles/

NOT-OD-01-041.html.

9\. National Institutes of Health. Tropical Storm Allison disaster
relief: Allowable costs under NIH and FEMA programs. (9 November 2001).
<http://grants2.nih.gov/>grants/guide/notice-files/NOT-OD-02-011.html.

**Lab Animal. 2000**;29(5):32‑37. OLAW and APHIS: Common Areas of
Noncompliance

STEPHEN POTKAY, VMD AND WILLIAM R. DEHAVEN, DVM

OLAW's Compliance Oversight: Noncompliance with PHS Policy

Stephen Potkay, VMD

The welfare of animals used in research has been a concern of the Public
Health Service (PHS) since the mid-1900s^1^. Section 495 of the Health
Research Extension Act of 1985 (HREA, Public Law 99B158)^2^ is the
statutory basis for the PHS Policy on Humane Care and Use of Laboratory
Animals^3^, and is the most significant legislation that directly
affects PHS.

The Office of Laboratory Animal Welfare (OLAW), formerly the Division of
Animal Welfare of the Office for Protection from Research Risks (OPRR,
see News Updates on p. 10), oversees compliance with the PHS Policy, and
its oversight extends to institutions that use live vertebrate animals
in research, research training, and biological testing activities
conducted or supported by the PHS. PHS includes the Agency for Health
Care Policy Research; the Agency for Toxic Substances and Disease
Registry; the Centers for Disease Control and Prevention; the Food and
Drug Administration (FDA); the Health Resources and Services
Administration; the Indian Health Service; the National Institutes of
Health; and the Substance Abuse and Mental Health Services
Administration.

The Institutional Promise

To receive PHS support for activities involving animals, each awardee
institution must provide a written Animal Welfare Assurance of
Compliance (Assurance) to OLAW, describing how it will comply with the
PHS Policy. OLAW carefully negotiates these Assurances to ensure that
the described institutional policies and practices are consistent with
the Policy, while giving consideration to the unique characteristics of
individual institutions.

OLAW approval of the Assurance commits the institution, its officials,
committees, investigators, and any of its other agents to full
compliance with provisions of the PHS Policy, including the US
Government Principles for the Utilization and Care of Vertebrate Animals
Used in Testing, Research, and Training (Principles)^4^, the Guide for
the Care and Use of Laboratory Animals (Guide)^5^, and, as applicable,
the Animal Welfare Act (AWA) Regulations^6^ and other federal statutes
and regulations applying to animals.

Institutional Self-Regulation and Other Monitoring

With respect to compliance with the PHS Policy, OLAW expects that
institutions will adhere to the promises made and procedures described
in their Assurances. Under the terms of approved Assurances,
institutions are required to send annual reports to OLAW describing any
changes that may have occurred in animal care and use programs, dates on
which program evaluations and facility inspections were conducted, and
minority views, if any. By signing the Assurance, the Institutional
Official (IO) also commits the institution to report promptly, along
with corrective actions taken, any serious or continuing noncompliance
with the Policy, any serious deviation from provisions of the Guide, and
any suspension of an activity by the Institutional Animal Care and Use
Committee (IACUC). In other words, institutions are expected to regulate
their own animal-related activities through oversight by their IACUC,
correcting instances of noncompliance and apprising OLAW of actions
taken. The record shows that this system of monitored institutional
self-regulation is highly successful, as the majority of recorded Policy
violations and infractions of the Guide have been brought to OLAW's
attention and corrected by the institutions themselves.

In addition, OLAW conducts site visits on short notice to randomly
selected institutions for the purpose of evaluating compliance and
providing technical assistance. The breadth and depth of oversight is
also enhanced by inspection activities conducted by other organizations
that notify OLAW of institutional activities that they believe to be in
violation of the PHS Policy. These include PHS funding components and,
under the terms of a 1995 Interagency Memorandum of Understanding, the
US Department of Agriculture (USDA) and the FDA^7^. OLAW's oversight
also extends to evaluating complaints and allegations received from any
other sources, including anonymous individuals, current and former
institutional employees, private individuals, animal-activist
organizations, and reports in the media.

Compliance Evaluations

On receipt of a complaint or report involving noncompliance with the PHS
Policy, OLAW first determines whether it has jurisdiction on the basis
of PHS support or an applicable Assurance, and whether the matter
involves alleged noncompliance with the PHS Policy or deviation from the
Guide. OLAW then acknowledges the institution's report if the matter was
self-reported or notifies the IO of possible noncompliance, and requests
a written response to the specific concern(s) by a specified date. When
a complainant is identifiable, OLAW generally requests the provision,
beforehand, of any and all evidence he or she may have to support the
allegations.

After evaluating the report submitted by the institution, and any other
information it has acquired, OLAW determines whether the matter has been
settled, and, if not, may request additional information. Most
compliance evaluations are resolved through correspondence, and do not
require site visits or formal reports. When noncompliance matters have
been concluded and OLAW determines that a formal report is in order,
copies of the report are submitted to the IO and the complainant(s) with
invitations to identify errors of fact. OLAW then appends and addresses
any factual errors in the preface and issues the report to the IO and
the complainant(s). Once issued, the report, with appendices, becomes
available under the Freedom of Information Act (FOIA).

Anonymity, Whistle-Blower Protections, and Other Issues

Complainants sometimes request anonymity or whistle-blower protection as
a condition of lodging a complaint. Although it is OLAW's policy not to
release predecisional documents pertaining to cases that are under
investigation or inquiry, most documents related to compliance-oversight
evaluations become publicly available under the FOIA when OLAW issues
its findings. In addition, the PHS Policy does not contain explicit
whistle-blower protections, and OLAW is not able to guarantee that
requests for anonymity or whistle-blower protection will be honored.
Accordingly, the decision of the complainant to provide personal
identifiers should be made on that basis. With regard to situations
involving USDA-covered species, on the other hand, the AWA Regulations
state that institutional personnel shall not be discriminated against or
subjected to any reprisal for reporting violations of any regulation or
standard under the AWA.

Although the purpose of the PHS Policy is to ensure the welfare of
animals involved in PHS-supported activities, animal care and use issues
are sometimes used as pretexts for involving OLAW in agendas that are
really focused on institutional personnel policies or actions, \"power
and turf\" issues, or interpersonal conflicts. OLAW notes that
responsibility for resolving these

kinds of problems is best left to the IOs and the other individuals
involved, with appropriate assistance from human resources personnel,
legal advisors, and facilitators.

Outcomes

The potential outcomes of inquiries and investigations are varied. Based
on the results of its evaluation, OLAW may determine that the
institution is either in compliance with the Policy, with or without the
requirement to consider recommendations for improvement, or that it is
not in compliance. In the latter instance, OLAW may restrict its
approval of the institution's Assurance in such a way as to ensure that
PHS-supported animal-related activities are not jeopardized, or it may
withdraw its approval of the Assurance. Without an approved Assurance,
facilities may not conduct PHS-supported activities involving animals.
Other possible outcomes include recommendations to PHS officials to
suspend or remove an institution from participation in specific
projects. Except in unusual circumstances, OLAW does not take action
against an institution without first notifying it of any identified
noncompliance with the Policy or deviation from the Guide, and giving it
reasonable opportunity to take corrective action in accordance with
provisions of the HREA.

Common Issues of Noncompliance

Failure to adhere to any provision of the Policy or the institutional
Assurance constitutes noncompliance. Inasmuch as some problems occur
more frequently than others, this section briefly describes some of the
more common and serious ones.

IACUC Constitution

Inadequacies in the constitution of IACUCs can seriously affect the
legitimacy of actions taken by the Committee, and constitute
noncompliance with the Policy. Most frequently these involve an IACUC
whose membership, because of member resignations, failure to replace
individuals whose terms have expired, or member deaths, lacks one or
more of the requisite members specified by and defined in the PHS Policy
(i.e., a veterinarian, a practicing scientist, a nonscientist, and a
person who is unaffiliated with the institution). In these cases, the
review and approval of animal-related activities, such as animal study
protocols, may be invalid and may require suspension until appropriate
review and approval have occurred.

A related problem is the absence of a convened quorum. Although the
previously mentioned members mandated by the Policy do not necessarily
have to be present at all meetings, the results of IACUC votes are valid
only when more than 50% of the members of the appropriately constituted
IACUC are in attendance. Careful attention to PHS Policy language
regarding IACUC membership, quorums, and functions should prevent these
problems from arising. In addition, appointing more than the minimum
number of members who meet the respective PHS Policy criteria (IV.A.3.b)
may prevent the occurrence of such problems when unexpected vacancies
arise.

Lack of IACUC Approval

The conduct of animal activities that have not been reviewed and
approved by an appropriately constituted IACUC is also a serious
problem, as is the implementation of significant changes to previously
approved activities without IACUC approval. These problems, and many
others, are often traceable to institutional training programs that fail
to adequately inform investigators of institutional and federal
policies, guidelines, and regulations, and that lack provisions for
periodic reinforcement or continuing education.

If an institution fails to establish ongoing monitoring systems to
ensure that the actual animal work being conducted is the same as that
which the IACUC approved, this also contributes to noncompliance in some
cases. While the vast majority of noncompliance issues have their
origins in a lack of understanding by investigators or other personnel
about their responsibilities, there are instances where they occur
because individuals either deliberately circumvent or choose to ignore
the provisions of the Policy or requirements of the Guide.

While the PHS Policy does not contain specific sanctions other than
suspension, most institutions have developed procedures for disciplining
such individuals to avoid the termination of specific grants by the
funding agency or the withdrawal of the institution's Assurance.
Institutionally imposed sanctions vary in severity from counseling,
temporary suspensions of privileges, and imposition of monitored
probation to permanent withdrawal of animal-use privileges and the
termination of employment.

Failure to Report

Institutions are expected to report promptly to OLAW any instances of
serious or continuing noncompliance with the Policy, serious deviations
from the Guide, and suspensions of animal-related activities, along with
descriptions of the corrective actions taken, in accordance with the PHS
Policy (IV.F.3) and the terms of their Assurances. Failures to report
usually appear as the result of carelessness or inattention to promises
contained in Assurances, misinterpretations of the term "serious," or
apprehension regarding self-incrimination and punitive measures that may
be imposed.

OLAW has provided guidance and given examples of serious incidents that
should be reported by IACUCs ^8,9^. It also reminds institutions that
Policy oversight is based on monitored self-regulation and that
considerations of adverse actions, as described above, are normally
activated only when institutions have been notified of, and fail to
correct, conditions that do not meet the requirements of the PHS
Policy^2^.

Post-Procedural Pain and Distress

Key provisions of the PHS Policy and the Principles are concerned with
avoiding or minimizing discomfort, distress, and pain in animals. In
OLAW's experience, problems in these areas most commonly involve aspects
of post-procedural care. In accordance with the Policy, all proposals
should be evaluated by the IACUC and when the potential for producing
discomfort, distress, or pain is found to exist, the IACUC is obligated,
in the absence of a written scientific justification, to insist that
appropriate measures (e.g., application of the three ARs^10^, use of
drugs, and provision of appropriate physical accommodations) will be
employed to avoid or minimize it.

OLAW finds that the deficiencies frequently entail failures of
investigators to communicate with technical, animal care, or veterinary
staffs, or assumptions that support personnel will automatically provide
the appropriate care. To prevent such a scenario from happening, IACUC
reviews should not only consider the appropriate chemical or physical
methods for preventing or alleviating post-procedural problems, but
should also ensure that suitable measures are in place for their
implementation, monitoring, and documentation. Establishment of clear
accountability is vital to prevention of deficiencies in this area.

Record-Keeping

Inadequate record-keeping, including the documentation of veterinary
care, is an issue that comes to OLAW's attention from its evaluations of
IACUC investigations, USDA inspection reports, and other sources.
Failures to document can be interpreted as failures to perform, and
bring into question the adequacy of IACUC monitoring and oversight. OLAW
suggests that documentation enhances credibility, and may be an
institution's or an individual's best defense against false accusations.

Complaint Mechanisms

Some complaints have their foundation in the absence of clear-cut,
credible institutional mechanisms whereby employees may bring their
concerns about animal care and use to the IACUC for consideration,
including assurances that there will be no reprisals for doing so. OLAW
has initiated a number of investigations in response to complaints that
could have been avoided, had those individuals originally recognized the
appropriate institutional procedures to express their concerns directly.

Education and Communication Channels

Many of the aforementioned compliance issues are directly related to
deficiencies in training and communication within the institutions.
Problems like these are largely preventable through ongoing education
programs that inform and update everyone who cares for or uses animals
(investigators, veterinarians, laboratory and veterinary technicians,
animal caregivers, IACUC members, etc.) of their individual obligations
with respect to institutional policies, procedures, and expectations, as
well as the requirements of the PHS Policy, the Guide, and the AWA
Regulations. Institutions can adapt published guidelines about training
in the humane care and use of laboratory animals^11^ to individual
institutional requirements, accounting for institutional size;
institutional complexity; numbers of people involved; numbers and
species used; and the nature of the research, testing, and educational
activities involved.

Summary

OLAW's compliance oversight is founded on negotiated
institution-specific Assurances and subsequent monitoring of
institutional self-regulatory activities, and is based secondarily on
the results of site visits and other sources of information. When OLAW
receives reports or allegations of instances of noncompliance with the
PHS Policy and determines that it has jurisdiction, it conducts an
evaluation that may take various forms. If OLAW verifies violations,
institutions receive notification and have an opportunity to take
appropriate corrective action. Written reports may or may not be issued
to document findings. Failure to comply with provisions of the Policy
may result in restriction or withdrawal of approval of an Assurance and
other actions initiated by funding agencies.

Unlike three or four decades ago, when physical plant and equipment
issues headed the list of institutional animal care problems, today's
compliance concerns tend to center around a number of inter-related
programmatic issues. Most commonly, these include the IACUC, its
composition, and the review of proposed and ongoing animal-related
activities; mechanisms to ensure that institutional policies and
procedures are implemented; record-keeping considerations; institutional
guidelines for registering concerns about animal care and use; prompt
reporting of instances of noncompliance; and effective training
programs.

Despite the complex nature of animal-based research, testing, and
teaching, most institutions can avoid potential pitfalls and achieve
compliance with the various regulations, policies, and guidelines that
apply to animal care and use by implementing appropriate administrative
and management mechanisms to ensure the effective execution of
institutional policies.

Potkay is Director of the Compliance Oversight Division, Office of
Laboratory Animal Welfare (OLAW), National Institutes of Health, 6705
Rockledge Dr., Rockledge I, Suite 1050-MSC 7982, Bethesda, MD
10892-1982. Please send reprint requests to Potkay at the above address.

References

1\. Gordon, H. The history of the Public Health Service Policy on Humane
Care and Use of Laboratory Animals. In: McPherson, C.W. and Mattingly,
S.F., eds. 50 Years of Laboratory Animal Science. American Association
for Laboratory Animal Science, Memphis, TN, pp 152B5, 1999.

2\. Health Research Extension Act of 1985, Public Law 99-158.
[Http://www.grants.nih.gov/grants/olaw/references/hrea1985.htm]{.underline}.

3\. Public Health Service. Policy on Humane Care and Use of Laboratory
Animals. US Department of Health and Human Services, Washington, DC,
1986.

4\. US Government Principles for the Utilization and Care of Vertebrate
Animals Used in Testing, Research, and Training. In: Policy on Humane
Care and Use of Laboratory Animals. US Department of Health and Human
Services, Washington, DC, p. i, 1996.

5\. National Research Council. Guide for the Care and Use of Laboratory
Animals. National Academy Press, Washington, DC, 1996.

6\. AWA Regulations, CFR, Title 9 (Animals and Animal Subproducts),
Subchapter A (Animal Welfare), Parts 1-3 (9 CFR 1-3).

7\. Memorandum of Understanding Among the Animal and Plant Health
Inspection Service, US Department of Agriculture and the Food and Drug
Administration, DHHS and the National Institutes of Health, DHHS
Concerning Animal Welfare. December 11, 1995.

8\. Potkay, S., et al. Frequently asked questions about the Public
Health Service Policy on Humane Care and Use of Laboratory Animals. Lab
Animal; 24(9):24-6, 1995.

9\. Garnett, N.L. and Ellis, G.B. Requirements for prompt reporting of
problems to OPRR. OPRR Reports, January 12, 1994.
Http://www.grants.nih.gov/grants/olaw/references/dc94-2.htm.

10\. Russell, W.M.S. and Burch, R.L. Principles of Humane Experimental
Technique. Charles C. Thomas, Springfield, IL, 1957.

11\. National Research Council. Education and Training in the Care and
Use of Laboratory Animals: A Guide for Developing Institutional
Programs. National Academy Press, Washington, DC, p. 139, 1991.

**USDA APHIS on AWA Compliance: Data Review and VMO Survey**

W. Ron DeHaven, DVM

The Animal Care (AC) division of the US Department of Agriculture (USDA)
Animal and Plant Health Inspection Service (APHIS) is responsible for
conducting inspections of biomedical research facilities registered
under the Animal Welfare Act (AWA). The recent upgrading of AC's
Licensing and Registration Information System (LARIS 8) permitted a
query of the database to determine the most common violations of the
regulations (Title 9, Code of Federal Regulations, Subchapter A, Animal
Welfare) documented in USDA inspections.

The USDA regulation violation search covered from January 1, 1998 to
January 10, 2000. LARIS 8 did not become completely functional until
October 1, 1999, and not all inspections conducted before October 1,
1999 had been retroactively entered into the system by the date of the
search. However, because the inspections entered were random and
recorded 873 violations, it is felt that the analysis of the data
(Table 1) is valid and provides meaningful insight into the relative
frequency of certain violations.

TABLE 1. Summary of research facility violations from January
1998-December 1999.

+-----------------------------------------------------------------+-----+
| IACUC                                                           | 322 |
|                                                                 | 153 |
| Facilities                                                      | 153 |
|                                                                 | 116 |
| Cleaning and Sanitizing                                         | 34  |
|                                                                 |     |
| Veterinary Care                                                 | 28  |
|                                                                 |     |
| Primary Enclosures                                              | 16  |
|                                                                 |     |
| Feeding                                                         | 12  |
|                                                                 |     |
| Miscellaneous                                                   | 11  |
|                                                                 |     |
| Personnel Qualifications                                        | 8   |
|                                                                 |     |
| Annual Report                                                   | 6   |
|                                                                 |     |
| Psychological Well-Being of Nonhuman Primates                   | 14  |
|                                                                 |     |
| Exercise of Dogs                                                | 873 |
|                                                                 |     |
| All Other                                                       |     |
|                                                                 |     |
| Total                                                           |     |
+-----------------------------------------------------------------+-----+

Due to creation of a new database, not all violations documented during
this period are included in this report. However, the violations were
randomly recorded and are therefore believed to consist of a valid
representation of the actual violations found on inspections during this
period.

IACUC Violations

One particular section of the regulations that deals with the
Institutional Animal Care and Use Committee (IACUC) system (\'2.31)
accounted for 322, almost 37% of the violations. The IACUC violations
can be further broken down (Table 2) into the specific paragraphs of
\'2.31 that were found to be in violation, with more than 70% violating
sections \'2.31(c) and \'2.31(d). The first area, \'2.31(c), is entitled
AIACUC Functions,@ and lists the specific activities that all IACUCs are
required to perform, specifically:

> Conducting semiannual reviews, inspections, and evaluations;
>
> Reviewing and investigating internal and external complaints regarding
> the care and use of animals at the institution;
>
> Making recommendations to the Institutional Official;
>
> Reviewing proposed animal care and use activities, as specified in
> \'2.31(d);
>
> Suspending animal care and use activities, as specified in
> \'2.31(d)(6).

The second area, \'2.31(d), is entitled AIACUC Review of Activities
Involving Animals,@ and includes all relevant activities related to the
protocol review process, such as approving protocols, requiring their
modification, annual review, review of significant changes, and protocol
suspensions. Fifty-five violations were recorded in a third area,
\'2.31(e), which addresses the five required components of every
protocol. These are:

> The identification of species and approximate numbers of animals;
>
> A rationale for involving animals and for the appropriateness of the
> species and numbers of animals to be used;
>
> A complete description of the proposed use of the animals;
>
> A description of procedures designed to limit animal discomfort and
> pain to that which is unavoidable;
>
> A description of any euthanasia method to be used.
>
> TABLE 2. Summary of IACUC violations from January 1998-December 1999.

+-----------------------------------------------------------------+-----+
| Appoint IACUC \[2.31(a)\]                                       | 9   |
|                                                                 |     |
| Membership \[2.31(b)\]                                          | 22  |
|                                                                 |     |
| Functions \[2.31(c)\]                                           | 117 |
|                                                                 | 110 |
| Protocol Review \[2.31(d)\]                                     |     |
|                                                                 | 55  |
| Protocol Components \[2.31(e)\]                                 |     |
|                                                                 | 9   |
| Not specified \[2.31\]                                          |     |
|                                                                 | 322 |
| Total                                                           |     |
+-----------------------------------------------------------------+-----+

Facilities and Cleaning & Sanitizing Violations

Violations in the Facilities and Cleaning and Sanitizing sections tied
for the second most common major areas of noncompliance. For each of
these areas, 153 violations were recorded, accounting for a total of 35%
of the violations. For the most part, the facility citations were
related to inadequate maintenance and repair of the physical plant, and
included items such as structural strength of the facilities; proper
storage of food and bedding; proper waste disposal; and protection from
the elements for animals housed outdoors. The Cleaning and Sanitizing
section of the regulations requires periodic cleaning and sanitizing of
primary enclosures, adequate housekeeping of the premises, and programs
for pest control.

Veterinary Care Noncompliance

Veterinary Care was the fourth most common area of major noncompliance
with 116 occurrences (13.3%). These citations include everything from
inadequate delivery of veterinary care to lack of a written program of
veterinary care for those facilities with a contract, part-time
veterinarian.

Comparison Survey

The results of the database query as it relates to IACUCs are consistent
with a recent survey of the AC Veterinary Medical Officers (VMOs) who
conducted these inspections, and their direct supervisors. All 49 VMOs
and their supervisors responded.

The VMOs and supervisors commented on the overall effectiveness of IACUC
regulations, and where improvements are needed. Of those surveyed, 94%
felt that the IACUC regulations are generally effective and that great
strides have been made in improving humane care and use of animals at
research facilities since the regulations were adopted. However, three
general areas were commonly identified as needing improvement:
acceptable consideration of alternatives to painful or distressful
procedures by the Principal Investigators; review of painful procedures
by the IACUC; and monitoring of animal use to ensure compliance with
approved protocols and institutional policies and procedures.

The respondents felt that AC needs to provide clear guidance to the
industry and to the VMOs on:

> What constitutes a painful or distressful procedure for AWA purposes;
>
> AC's expectations on how facilities should minimize pain and distress;
>
> How to appropriately report various painful and distressful procedures
> under the current categorization scheme.

Future Plans

AC has already initiated action to address most of these concerns. All
VMOs attended a work conference from late February through early March
dealing specifically with inspection of registered research facilities.
Many outside experts were included on the agenda, and much of the
program dealt with the issues identified above. Additionally, AC is
currently in the process of revising Policy #11 (Painful/Distressful
Procedures) to clarify the definition and reporting, and Policy #12
(Written Narrative for Alternatives to Painful Procedures) to clarify
expectations for the consideration of alternatives.

By identifying the most common areas of noncompliance with the AWA
regulations, and clarifying our expectations for these areas, it is our
hope that AC and the lab animal community can work together to improve
compliance with the regulations and promote the well-being of research
animals.

Dr. DeHaven is the Deputy Administrator for Animal Care, US Department
of Agriculture, Animal and Plant Health Inspection Service, 4700 River
Rd., Unit 97, Riverdale, MD 20737-1234. Please send reprint requests to
DeHaven at the above address.

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**Contemporary Topics. 1997; 36(2):47‑50. FAQs about the PHS Policy on
Humane Care and Use of Laboratory Animals**

Authors: STEPHEN POTKAY, VMD, NELSON GARNETT, DVM, JOHN G. MILLER, DVM,
CYNTHIA L. POND, DVM, MS, and DENIS J. DOYLE, MA

Division of Animal Welfare, Office for Protection from Research Risks,
National Institutes of Health, 6100 Executive Boulevard, Suite 3B01, MSC
7507, Rockville, MD 20892‑7507.

Abstract: Adherence to the provisions of the Public Health Service (PHS)
Policy on Humane Care and Use of Laboratory Animals and related U.S.
Department of Agriculture Animal Welfare regulations is a prerequisite
for receiving PHS support for conducting animal‑related activities. As
one of its duties specified in the PHS Policy, the Office for Protection
from Research Risks (OPRR) here provides guidance regarding questions
that have been raised by institutions seeking to comply with those
requirements. These questions include institutional reporting
requirements, collaborative activities, performance of multiple survival
surgeries, care and use of cold‑blooded vertebrates, tracking of animal
use, animal study areas, and other Animal Care and Use Committee issues.
In reviewing these questions and answers, readers are asked to keep in
mind

that many of these issues are highly context‑specific and that
over‑generalization is to be avoided.

The Office for Protection from Research Risks (OPRR) of the National
Institutes of Health (NIH) develops, implements, and oversees compliance
with the Public Health Service (PHS) Policy on Humane Care and Use of
Laboratory Animals (1). The PHS Policy and the U.S. Department of
Agriculture (USDA) Animal Welfare Regulations (2) are the two principal
federal documents setting forth requirements for animal care and use by
institutions that use animals in research, testing, and education. One
of the primary functions of OPRR is to assist institutions in
implementing PHS Policy by responding to policy‑related questions (3‑5).
The following are several questions frequently asked by institutions and
the OPRR responses.

**1. Could you provide examples of \"significant\" and \"minor\"
deficiencies and suggest appropriate methods for reporting them in the
Institutional Semiannual and Annual Reports?**

The term \"significant deficiency,\" used in the PHS Policy and the USDA
Animal Welfare Regulations, refers to any facility or program deficiency
that is or may be a threat to the health or safety of animals. Program
or facility deficiencies, including accidents and natural disasters,
which cause injury, death, or severe distress to animals, are, by
definition, \"significant.\" Although it is not possible to provide an
exhaustive listing of examples, some illustrations of significant
facility deficiencies include failures in heating, ventilating, and air
conditioning systems and their associated electrical systems;
inoperative watering systems; and general power failures of sufficient
duration to affect critical areas such as isolators, barriers, surgical
suites, and intensive care units. Minor deficiencies in animal
facilities include infrequent findings of peeling or chipped paint,
burnt‑out light bulbs, missing floor drain covers, and similar problems
for which immediate solutions generally are not necessary to protect
life or prevent distress. Repeated detection of minor, area‑specific
problems, however, should suggest to management that there are
substantial program deficiencies resulting failure to develop effective
policies or plans or to take corrective actions to prevent recurrences.

Significant program deficiencies generally originate in an
institution\'s failure to fully understand or implement some aspect of
its animal care and use program, as required by the PHS Policy (6). Most
commonly, they are related to failure of the Institutional Animal Care
and Use Committee (IACUC) to function according to commitments made in
its institutional assurance. Specific difficulties often are connected
with the animal research proposal review process, veterinary care, or
institutional training programs, inadequacies of which may pose real or
potential threats to the

health or safety of animals.

Institutional semiannual reports should categorize any deficiencies
found during the IACUC\'s semiannual program and facility review as
being major or minor. For both categories, a reasonable and specific
plan must be described for the correction of each deficiency and a
schedule for accomplishing the correction. When deficiencies involve
serious or continuing noncompliance with the PHS Policy, serious
deviations from the Guide for the Care and Use of Laboratory Animals
(henceforth referred to as the Guide)(7), or the IACUC suspension of any
activity, the circumstances and actions taken must be reported promptly
to OPRR as required in section IV.F.3.a‑c. of the PHS Policy. Reporting
of such deficiencies should not be deferred for inclusion in the
institutional annual report. It also should be noted that the USDA
Animal Welfare Act regulations require that significant deficiencies not
corrected within the time frame of the initial corrective plan and
schedule be reported within 15 business days to the Animal and Plant
Health Inspection Service (APHIS) and to any Federal agency funding that
activity.

**2. Investigators at our institution often collaborate with scientists
in other countries and sometimes go abroad to collect samples from
captive wild animals maintained in zoological collections and in
research colonies. Is it necessary for our IACUC to review and approve
their protocols? What about samples that are obtained by citizens of the
foreign country and sent to our institution?**

All animal activities supported by the PHS must be reviewed by the IACUC
of the domestic‑assured awardee institution that receives such support.
Foreign institutions that serve as performance sites must also have
Assurances on file with OPRR. The OPRR considers institutions whose
scientists are engaged in such collaborative work accountable for the
animal‑related activities from which they receive animals or animal
parts. When a foreign institution holds a PHS Assurance, it also is
expected that the institution will conduct the study in accordance with
the applicable host‑nation\'s policies and regulations. In the specific
case of sample collection, the review should take into account the
species involved, nature of the specimen, and the degree of invasiveness
of the procedure, giving appropriate consideration to the use of
anesthetics and analgesics. In cases in which samples are obtained
directly by citizens of a foreign country for subsequent shipment,
recipient PHS‑supported investigators should determine the proposed
methods of collection and present that information to their IACUC for
review. Prior to sample collection and regardless of whether specimens
are obtained by an awardee institution\'s investigator directly or by
persons in a foreign country, the OPRR strongly recommends that each
awardee institution consult with other agencies of the U.S. government
concerning importation requirements. Depending on the species involved
and the nature of the specimen, the following may be of assistance: the
U.S. Fish and Wildlife Service, Department of the Interior (for
compliance with the International Convention on Trade in Endangered
Species of Fauna and Flora \[CITES\]), APHIS, U.S. Department of
Agriculture (regarding potential animal pathogens), and the Centers for
Disease Control and Prevention (concerning importation of nonhuman
primates and potential pathogens of human beings).

**3. The PHS Policy requires that the IACUC consist of at least 5
members, whereas the Health Research Extension Act states that the
committee be composed of at least 3 members. Regulations of the Animal
Welfare Act are consistent with the latter. In constituting our
committee, which requirement should we adhere to? Also, would you
explain the difference between Institutional Official and Chief
Executive Officer (CEO)?**

When your institution is a recipient of PHS support for animal‑related
activities, its IACUC must consist of at least 5 members who are
appointed by the institution\'s CEO. It is required that these
individuals be qualified through experience and expertise to provide
oversight for the institution\'s animal programs, facilities, and
procedures. At a minimum, IACUCs must include a veterinarian, a
practicing scientist experienced in animal research, a person whose
primary concerns are in nonscientific areas, and a person who is
unaffiliated with the institution except as a member of the IACUC. It
should be noted that the unaffiliated individual may not be a member of
the immediate family of a person who is affiliated with the institution.
The veterinarian, in addition to possessing training or experience in
laboratory animal science and medicine, must have direct or delegated
program responsibility for animal‑related activities at the institution.
Although an individual who qualifies to fill more than one of the
aforementioned categories may be appointed to do so, it is still
required that the committee consist of 5 members. For purposes of the
PHS Policy, the institutional official is that person in the
organization having the administrative and operational authority to
commit institutional resources to ensure that the animal care and use
program will comply with requirements of the PHS Policy. In some
institutions, the institutional official and the CEO may be one and the
same, whereas in other institutions, particularly large ones, the CEO
may be further removed from the day‑to‑day program oversight.

**4. To describe the responsibilities and qualifications of
veterinarians who will participate in our animal program, will the
provision of a curriculum vitae suffice? May the veterinarian be
unaffiliated with the institution?**

It has been OPRR\'s experience that curricula vitae of veterinarians
provided with the submissions of new or renewal Assurances of Compliance
usually do not contain the specific information required by the PHS
Policy. Therefore, this office recommends that Section III.B. of the
Assurance be used to provide the names, professional degrees, and the
number of years of pertinent training in laboratory animal medicine for
each veterinarian participating in the animal care and use program. An
indication of the individuals\' training and experience in managing the
species involved also is helpful. This should be followed by a
description of the duties and responsibilities of those persons and a
statement regarding the direct or delegated authority of the individuals
to implement the PHS Policy and the provisions of the Guide. It also is
important to indicate the approximate percentage of time that those
individuals will contribute to the program. In cases in which there is
not a full‑time veterinarian on the staff, the anticipated number and
frequency of visits by the veterinarian should be indicated. Failure to
provide the required information will necessitate follow‑up requests by
OPRR and can result in lengthy processing delays.

In all cases, the veterinarian responsible for implementing the program
is, by definition, affiliated with the institution, whether as an
official employee or through a written contract for service. It may be
noted that some institutions find it helpful to retain the services of a
Diplomate of the American College of Laboratory Animal Medicine who is
available to consult with its institutional veterinarian for the
resolution of certain problems (8).

**5. Our IACUC has received a proposal in which nonhuman primates from
our institution\'s breeding colonies would be subjected to multiple
cesarean sections in order to obtain viable offspring and to maximize
cost effectiveness and the reproductive utility of the colony of a
threatened species. Because cesarean sections commonly are performed in
other species such as companion animals, will our IACUC have to consider
the proposal in the context of a multiple survival surgery?**

While discouraging the performance of multiple survival procedures on
specific animals, the Guide states that the IACUC may consider special
circumstances involving requests to do so. An example of a potentially
justifiable request given in the Guide involves performing multiple
procedures on an animal when the procedures are related components of a
research project. The USDA Animal Welfare Regulations, which are
applicable under the PHS Policy, provide further guidance on this
matter. Under the regulations, multiple major operative procedures are
permitted when 1) scientifically justified by the investigator (in
writing) and approved by the IACUC or 2) when needed as a routine
veterinary procedure or to protect the health and well‑being of an
animal, as determined by the attending veterinarian. Proposals that
involve exposing an animal to multiple major surgery under conditions
not covered by items 1 or 2 must receive prior authorization by the
Administrator, APHIS, USDA. When considering proposals such as the one
described, specific requests should be made to APHIS on a cases‑by‑case
basis. In its evaluation of such requests, the IACUC must understand
that it was the intent of Congress to prohibit subjecting animals to
multiple major (survival) surgeries in unrelated research protocols, and
that species that are threatened or endangered were not distinguished
from those that are not on a threatened or endangered list. Neither the
PHS Policy nor the USDA Regulations consider cost savings alone as an
adequate justification for performing multiple major surgeries on an
animal.

**6. Use of amphibians, reptiles, and fishes in research appears to be
increasing at our institution. However, neither the PHS Policy nor the
Guide provide specific guidelines for our IACUC to follow in its
consideration of research proposals involving the care and use of these
animals. What advice can OPRR offer to assist our IACUC?**

The PHS Policy is intentionally broad in scope and does not prescribe
specifics about the care and use of any species, assigning that task to
the IACUC and allowing for professional judgment. Many of the principles
embodied in the Guide, although not specifically addressing cold‑blooded
vertebrates, generally can be adapted to animal care and use programs
for various kinds of amphibians, reptiles, and fishes. Substantive
guidance pertinent to specific species and situations is available in
publications prepared by organizations having interest in the
appropriate care and use of these species in laboratory and field
studies (9‑18). It is clear, however, that individual requirements for
these 3 classes of vertebrates, which contain more than 28,000 species
that have a diversity of requirements, cannot be addressed in a single
set of guidelines. Consequently, the OPRR recommends that the advice of
experts be obtained to design and develop studies and suitable housing
and care procedures when species not commonly used in research are being
considered. The OPRR also suggests that the results of their efforts to
devise methods for the

care and use of these species be published to serve as an aid to others.

**7. Is it necessary for our IACUC to track the numbers of animals used
in the various protocols it has approved to ensure that the numbers do
not exceed those that were approved in the proposal review process? If
so, could you provide guidance on the best means for accomplishing
this?**

Although neither the PHS Policy nor the USDA regulations explicitly
require an institutional mechanism to track animal usage by
investigators under IACUC‑approved activities, both require that
proposals to the IACUC specify and include a rationale for the
approximate number of animals proposed to be used. These provisions
implicitly require that institutions establish mechanisms to monitor and
document the number of animals acquired and used in approved activities.
The OPRR is aware of many institutions at which such mechanisms preclude
an investigator from using a single animal in excess of the number
approved by the IACUC. Other institutions have reported mechanisms that
allow the number of rodents acquired to exceed the number approved by a
small percentage (e.g., 5%), although they still may require
investigators to obtain and use only the precise number of nonrodent
mammalian species approved by the IACUC.

Administrative linkage of animal acquisitions to IACUC approval numbers
is the method of choice used by many institutions to track the numbers
of animals being acquired under approved activities. Many also have
described relatively simple automated data processing systems that will
alert the systems\' operator and generate a report when an investigator
has reached a preset percentage (e.g., 80‑90% of the animals approved
for that activity). This report then is submitted to the investigator
with a request to provide a specific justification if they anticipate
that the number of animals ultimately required will exceed the number
approved. Small institutions that use limited numbers of animals may
choose to maintain a hard‑copy log of each IACUC‑approved activity,
merely subtracting the number of animals acquired for each order from
the number approved, with verbal or written notification to the
investigator as the number of animals approved is approached. Whatever
mechanism an institution chooses, however, it must satisfy the PHS
Policy requirement that the number of animals used be limited to the
appropriate number necessary to obtain valid results.

**8. In conducting its semiannual facility reviews, is it necessary for
our IACUC to consider laboratories or other sites where animal
procedures or holding activities are conducted only sporadically or for
periods of less than 24 h? How does our IACUC determine whether to
follow the requirements of the PHS or the USDA regarding the definition
of \"study area?\"**

Each assured institution, acting through its IACUC or facility
veterinarian, is responsible for all animal‑related activities at the
institution regardless of where the animals are maintained or the
duration of their stay. The degree, frequency, and method of IACUC
oversight often depends on the nature of the activity. For example,
satellite holding facilities and areas in which surgical manipulations
are performed must always be included in semiannual reviews, whereas
laboratories in which only routine immunization, dosing, and weighing
take place may be monitored by other means such as random site visits
and evaluations. Regardless of whether such laboratories are included in
the semiannual review process or are monitored by other means, the IACUC
must have reasonable access to them for the purpose of verifying that
activities involving animals are being conducted in accordance with the
proposal approved by the IACUC. The PHS Policy requires compliance with
the USDA regulations regarding areas where USDA‑covered species are
maintained for any purpose for more than 12 h. The term \"satellite
facility\", as defined in the PHS Policy, remains unchanged and is
applicable to the housing or holding facilities provided for all
vertebrate animals. It is important to keep in mind that the institution
is accountable for all activities involving animals, regardless of
technical differences in definitions and time limits, and that
institutional policies should be designed to obtain the desired outcome
of both the PHS Policy and the Animal Welfare Act (namely, the
appropriate, humane care of all animals at each institution).

REFERENCES

1\. Public Health Service. 1996. Public Health Service Policy on Humane
Care and Use of Laboratory Animals. U.S. Department of Health and Human
Services, Washington, D.C. \[Reprint of 1986 edition\].

2\. Animal Welfare Regulations. 1985. Code of federal regulations, title
9 (animals and animal subproducts), subchapter A (animal welfare), parts
1‑3 (9 CFR 1‑3). U.S. Department of Agriculture, Washington, D.C.

3\. Division of Animal Welfare, Office for Protection from Research
Risks. 1991. The public health service responds to commonly asked
questions. ILAR News 33:68‑70.

4\. Division of Animal Welfare, Office for Protection from Research
Risks. 1993. Frequently asked questions about the public health service
policy on care and use of Laboratory Animals. ILAR News 35:47‑49.

5\. Potkay, S., N. L. Garnett, J. G. Miller, et al. 1995. Frequently
asked questions about the public health service policy on humane care
and use of laboratory animals. Lab. Animal. 24:24‑26.

6\. McLaughlin, R M. 1993. Institutional animal care and use committee
review of animal care ad use programs. Contemp. Top. Lab. Anim.
32:12‑15.

7\. National Research Council. 1986. Guide for the care and use of
laboratory animals. NIH Publication No. 86‑23. Public Health Service,
Washington, D.C.

8\. American College of Laboratory Animal Medicine. 1996. Report of the
American College of Laboratory Animal Medicine on adequate veterinary
care in research, testing, and teaching. American College of Laboratory
Animal Medicine, Cary, NC.

9\. Ferguson HW. 1984. Fish, p. 1‑10. In: Guide to the care and use of
experimental animals, vol 2., Canadian Council on Animal Care, Ottawa,
Ontario, Canada.

10\. Institute for Laboratory Animal Resources. 1974. Amphibians. In:
Guidelines for the breeding, care and management of laboratory animals.
National Academy of Sciences, Washington, D.C.

11\. Institute for Laboratory Animal Resources. 1991. Recommendations
for the care of amphibians and reptiles in academic institutions.
National Academy of Sciences, Washington, D.C.

12\. Scientists Center for Animal Welfare. 1992. The care and use of
amphibians, reptiles, and fish in research. Schaeffer, D. O., K. M.
Kleinow, L. Krulisch (eds.). Scientists Center for Animal Welfare,
Greenbelt, MD.

13\. American Society of Ichthyologists and Herpetologists, American
Fisheries Society, American Institute of Fisheries Research Biologists.
1987. Guidelines for the use of fishes in field research. Fish. J.
13(2):1‑14.

14\. American Society of Ichthyologists and Herpetologists, The
Herpetologists\' League, and Society for the Study of Amphibians and
Reptiles. 1987. Guidelines for the use of live amphibians and reptiles
in field research. J. Herpetology (Suppl) 4:1‑14.

15\. Orlans, F. B. 1988. Field research guidelines: impact on animal
care and use committees. Scientists Center for Animal Welfare,
Greenbelt, MD.

16\. DeTolla, L. J., S. Srinivas, B. R. Whitaker, et al. 1995.
Guidelines for the care and use of fish in research. ILAR J. 37:159‑173.

17\. DeNardo, D. 1995. Amphibians as laboratory animals. ILAR J.
37:173‑181.

18\. Greene, H. W. 1995. Nonavian reptiles as laboratory animals. ILAR
J. 37:182‑186.

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**Contemporary Topics. 1996**; 35(5):53‑56. Model for Performing
Institutional Animal Care and Use Committee: Continuing Review of Animal
Research

GWENN S.F. OKI, MPH (1), ERNEST D. PRENTICE, PHD (2), NELSON L. GARNETT,
DVM (3), DALE F. SCHWINDAMAN, DVM (4), and CAROL Y. WIGGLESWORTH (5)

\[(1) Director, Research Subjects Protection, Research Administration,
City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA
91010-3000; (2) Associate Dean for Research, University of Nebraska
Medical Center, 600 South 42nd Street, Omaha, NE 68198-6810; (3)
Director, Division of Animal Welfare, Office for Protection from
Research Risks, 6100 Executive Boulevard, Suite 3B01, MSC 7507,
Rockville, MD 20892; (4) Deputy Administrator, United States Department
of Agriculture, Animal and Plant Health Inspection Service, Regulatory
Enforcement and Animal Care, 4700 River Road, Unit 97, Riverdale, MD
20737-1234; (5) Senior Policy Analyst, Division of Animal Welfare,
Office for Protection from Research Risks, 6100 Executive Boulevard,
Suite 3B01, MSC 7507, Rockville, MD 20892\]

[Abstract]{.underline}: Although institutional animal care and use
committee (IACUC) continuing review of ongoing animal related activities
is a requirement imposed by the Public Health Service Policy (PHS
Policy) and United States Department of Agriculture (USDA) animal
welfare regulations, there is lack of uniform understanding and
application of these federal requirements. This paper endeavors to
clarify the purpose and substance of continuing review through
exploration of the requirements of the PHS Policy and the USDA
regulations. It proposes a model that incorporates a practical,
meaningful, and reasonable method of performing continuing review which
institutions can adopt or modify to suit their individual needs.

The Public Health Service Policy (PHS Policy) (1) and the United States
Department of Agriculture Rules (USDA regulations) (2) require the
institutional animal care and use committee (IACUC) to perform initial
and continuing review of animal related activities. The term \"animal
related activities\" refers to research, testing, teaching, training and
related activities, which involve use of animals. As a result of
discussions with IACUC administrators, the Office for Protection from
Research Risks (OPRR) and the USDA, it has become evident that there is
a lack of uniform understanding of the PHS and USDA requirements for
continuing review of ongoing activities involving animals. Through
exploration of the regulatory requirements, we sought to clarify the
meaning of continuing review and to propose a review model that
institutions can use or adapt to their own specific needs and
circumstances. Thus, this review model is presented with the
understanding that institutions must be allowed flexibility in designing
and implementing continuing review processes that are suited to their
individual animal care and use programs.

**REGULATORY REQUIREMENTS**

The PHS Policy at IV.C.5. states \"the IACUC shall conduct continuing
review of activities covered by this policy at appropriate intervals as
determined by the IACUC but not less than once every three years (3)\".
The USDA regulations 9 CFR 2.31(a)(5) (4) use similar language, except
that continuing review must be performed not less than annually.

The OPRR has interpreted the PHS Policy provision for continuing review
as a requirement for a \"de novo\" review (5-7). In this context, \"de
novo\" means that the criteria and procedures for review of projects
specified in IV.C. of the PHS Policy must be applied not less than once
every three years. The IACUC must make the determination that the
project conforms with the criteria at IV.C.1.a-g. of the PHS Policy.
These criteria address such factors as pain and distress, pain relief,
animal husbandry, veterinary care, personnel qualifications and methods
of euthanasia. In addition to confirmation that projects are in
compliance with the PHS Policy, the IACUC must also determine that the
project is being conducted in a manner consistent with the \"Guide for
the Care and Use of Laboratory Animals\" (Guide), unless departure is
justified.

The preamble to the USDA regulations provides guidance on the USDA
requirement for annual continuing review as follows: \"We are adding a
provision to the Final Rule to require that the Committee conduct
continuing review of activities covered by the Animal Welfare
Regulations at appropriate intervals, and at least annually \[Final Rule
2.31(d)(5)\]. This review\...is intended to provide current information
to the Research Facility regarding all ongoing activities so it can
remain in compliance\" (8).

The USDA interprets the role and purpose of the annual continuing review
as one form of monitoring the use of animals. Monitoring can be
accomplished by the use of a standard form containing basic protocol
information to be provided by the investigator (status of the project,
assurance that activities are being conducted in accordance with the
approved protocol, and proposed departures from the protocol in the
upcoming year). It should be noted that the USDA regulations \[9 CFR
Part 2, Subpart C, 2.31(c)(7); 2.31(d)\] and the PHS Policy \[IV.C.1\]
require that proposed significant changes to the currently approved
protocol be reviewed and approved by the IACUC prior to implementation.

**THE PURPOSE AND SUBSTANCE OF CONTINUING REVIEW**

On the basis of the aforementioned regulatory requirements and our
collective interpretation, the purpose of continuing review appears to
be threefold: to inform the IACUC of the current status of the project;
to ensure continued compliance with PHS, USDA and institutional
requirements; and to provide for re-evaluation of the animal activities
at appropriate intervals. Federal requirements, research ethics, and
moral obligations of the scientific community to society demand that
IACUCs conduct appropriate and meaningful reviews of ongoing animal
protocols in the same responsible manner that initial reviews are
effected. This means that IACUCs should not \"rubber stamp\" a
previously approved protocol during continuing review just because it
has undergone a thorough initial review. In a society where use of
animals in research, testing and teaching is viewed with increasing
concern (9), high standards of oversight must be maintained. Within the
framework of federal regulations and policies, however, there is need
for institutions to develop review procedures that are reasonable,
meaningful and efficient, and that do not burden IACUCs or investigators
with unnecessary requirements that do not contribute directly to the
welfare of the animals or provide significant information relevant to
the role of the IACUCs.

**Current status of the project:** Information concerning the current
status of the project should be provided by the investigator to the
IACUC. Logically, this information would include funding status, number
of animals used, and proposed amendments. In addition, some IACUCs may
choose to ask the investigator to submit a brief report that will update
the Committee on the progress being made on achieving the specific aims
of the protocol. In general, however, progress reports or updates should
not be used in the context of an assessment or evaluation unless there
is an indication that the animal use is not consistent with good
science.

**Compliance with PHS, USDA and institutional requirements:** The
investigator should provide assurance that the animal activity has not
deviated from the current IACUC approved protocol. Although it may
generally be assumed that the initial review constituted a thorough and
in depth assessment of the protocol for compliance with the requirements
in place at the time, changes may have occurred in IACUC policies and
procedures, the \"state of the art\", as well as in the PHS Policy and
the USDA regulations. Therefore, protocols should be updated and
reviewed, as necessary, to comply with the current standards.

**Ethical cost-benefit analysis:** Animal activities are most frequently
justified from an ethical cost-benefit perspective. This means that any
animal pain, morbidity and mortality must be outweighed or at least
balanced, by the potential benefits of the project in terms of its
relevance to human or animal health, advancement of knowledge or the
good of society (10). Ethical cost-benefit assessment should be a major
focus during initial and continuing review by the IACUC (10,11). This
assessment should not, however, be misconstrued as the equivalent of an
NIH study section review of scientific merit. Instead, it represents a
threshold level of review which documents that the use of animals
continues to be justified. Without such assessment, there is lack of
accountability, which negates the purpose of continuing review,
particularly for projects not funded by the PHS or other funding
agencies with rigorous peer review.

The obvious question which arises is why an ethical cost-benefit
relationship would change over time. After a protocol is initially
approved by the IACUC it is possible that new information may have
become available, which allows application of one of the \"three Rs\"
(reduction, refinement, replacement). For example, new in vitro
techniques or statistical methods may be discovered that could reduce
the number of animals required. Or an investigator may find that a
lesser degree of morbidity can be used as an experimental end point.
Conversely, in some situations, it may be necessary for scientific
reasons to increase the number of animals or to allow animals to reach a
more advanced stage of morbidity than originally specified in the
protocol. In either case, the ethical cost-benefit ratio will be altered
and the IACUC should, therefore, re-evaluate this new relationship.
Proposed changes in the protocol can be considered during continuing
review and approved as warranted. Admittedly, there are considerations
related to scientific continuity and grant requirements that may dictate
whether changes in a protocol are possible. Nonetheless, it is incumbent
on investigators and IACUCs alike to determine during continuing review
whether the 3Rs can be applied further to the protocol.

**ONE METHOD FOR PERFORMING CONTINUING REVIEW**

**Combining PHS and USDA review procedures:** Many institutions have
sought to simplify their continuing review process by combining the
requirements of both the PHS Policy and the USDA regulations. At some
institutions, this can be accomplished most easily by satisfying the
admittedly more stringent PHS Policy continuing review requirements, on
an annual basis rather than triennially, thereby eliminating the dual
tracking system for the one- and three-year cycles. However,
comprehensive annual reviews may not be administratively feasible at
large institutions, although, it should be remembered that both the PHS
Policy and the USDA regulations also specify that continuing review be
performed \"at appropriate intervals\...\". Thus, it is possible that an
IACUC may decide that a project should be reviewed more often than
annually.

To satisfy the requirements of the PHS Policy, the method of performing
continuing review must conform to one of the two procedures described in
the PHS Policy \[IV.C.2.\], that is: review by the \"full committee\" or
use of the \"designated reviewer\" process. The OPRR accepts the review
as being \"de novo\" if it includes, in accordance with IV.C. of the PHS
Policy, a review of complete, current information about the animal
activity and follows one of the two procedures described previously.
Accordingly, if nothing has changed in the original protocol, review and
approval of the continuing review form and the original protocol at
appropriate intervals, following the prescribed procedures, also
satisfies the PHS Policy requirement for triennial \"de novo\"
continuing review as well as the USDA annual review requirements.

**The IACUC continuing review form:** To conduct practical, reasonable,
and meaningful continuing review of animal activities, which would
satisfy both USDA regulatory and PHS Policy requirements, two of the
authors (GSFO, EDP) propose the use of the following form (which has
been labeled with section and item numbers, and corresponding
explanations).

**INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC)**

***CONTINUING REVIEW FORM***

PROTOCOL
TITLE:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

IACUC#:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ DATE OF INITIAL
APPROVAL:\_\_\_\_\_\_\_\_\_\_\_\_\_\_

PRINCIPAL INVESTIGATOR:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

DEPARTMENT:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

CAMPUS
ADDRESS:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
PHONE: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

> . **RECORD OF ANIMAL USAGE**

  ----------------------------- -------------------- --------------------
  **Species**                   **Total \#           **\# Used to Date**
                                Approved**           

                                                     

                                                     

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

> **. NATURE OF THE PROTOCOL/STUDY. (Check \[ X \] all applicable
> items.)**

  ---- ------------------- ---- ----------------- ---- -------------------------
  \[   Survival (Chronic)  \[   Prolonged         \[   Inducement of a Disease
  \]   Study               \]   Restraint         \]   State

  \[   Terminal (Acute)    \[   Neuromuscular     \[   Inducement of Behavioral
  \]   Study               \]   Blockers          \]   Stress

  \[   Multiple Surgeries  \[   Antibody          \[   Blood/Tissue Collection
  \]                       \]   Production        \]   

  \[   Transgenic Breeding                             
  \]                                                   
  ---- ------------------- ---- ----------------- ---- -------------------------

> . **\[USDA\] PROJECT (Pain) CATEGORY \[ X \]:** \[ \] C \[ \] D \[ \]
> E
>
> \- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
> -
>
> . **PROTOCOL STATUS.** Please indicate ( X ) the status of this
> project.
>
> [Request Protocol Continuance]{.underline}
>
> A. Active - project ongoing.
>
> B. Currently inactive - project was initiated but is presently
> inactive.
>
> C. Inactive - project never initiated but anticipated start date is
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
>
> [Request Protocol Termination]{.underline}
>
> D. Inactive - project never initiated.
>
> E. Currently inactive - project initiated but project has not/will not
> be completed.
>
> F. Completed - no further activities with animals will be done.
>
> **FUNDING SOURCE:** Specify the funding source.
>
> **PROJECT PERSONNEL.**

  ---- ------ ---------------------------------------------------------------
  \[   Yes:   Have there been any personnel/staff changes since the last
  \]          IACUC

              approval was granted?
  ---- ------ ---------------------------------------------------------------

  ---- ----- ---------------------------------------------------------------
  \[   No:   If yes, please complete the following sections
  \]         (Additions/Deletions).

             For additions, please submit a completed Personnel
             Qualification

             Statement with this Continuing Review Form and make
             arrangements

             with the Animal Resources Center staff for inservice training
             on the

             proper care and handling of laboratory animals.
  ---- ----- ---------------------------------------------------------------

> **Additions:** Name/Role/Responsibility for Project
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

  ---------------- ------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------------------------------------------------------------------------
  **Deletions:**   Name\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_   Effective
                                                                                                                                                              Date\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

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

> **PROGRESS REPORT.** If the status of this project is 4.A. (active;
> project ongoing) or 4.B. (project was initiated, but is presently
> inactive), provide a brief update on the progress made in achieving
> the specific aims of the protocol.
>
> **PROBLEMS/ADVERSE EVENTS.** If the status of this project is 4.A.
> (active; project ongoing) or 4.B. (project was initiated, but is
> presently inactive), describe any unanticipated adverse events,
> morbidity or mortality, the cause(s), if known, and how these problems
> were resolved. If NONE, this should be indicated.
>
> **ALTERNATIVES TO ANIMAL USE.** Alternatives to the use of animals
> should be considered and used when possible. Since the last IACUC
> approval, have alternatives to the use of animals become available
> that could be substituted to achieve your specific project aims?
>
> **ALTERNATIVES TO POTENTIALLY PAINFUL PROCEDURES.** (Address the
> following if your project involves USDA Category D or Category E.)
> Procedures that cause the least amount of pain or distress to the
> animals should be considered and used when possible. Since the last
> IACUC approval, have alternatives which are potentially less painful
> or distressful become available that could be used to achieve your
> specific project aims?
>
> **DUPLICATION.** Activities involving animals must not unnecessarily
> duplicate previous experiments. Provide written assurance that the
> activities of this project remain in compliance with the requirement
> that there must be no unnecessary duplication.
>
> **FUTURE PLANS.**
>
> No changes are planned and the project will continue as previously
> approved by the IACUC.
>
> Changes are planned. Provide a full description and justification for
> the proposed changes. (A copy of the IACUC Protocol Amendment Form has
> been included for this purpose.)
>
> \[Please note that if the modifications are significant, you may be
> required to complete a new application. If you have questions or
> require assistance in making this determination, please contact the
> IACUC Office and/or the Attending Veterinarian.\]
>
> Other. Provide a brief explanation.

**CERTIFICATION OF THE PRINCIPAL INVESTIGATOR.** Signature certifies
that the Principal Investigator understands the requirements of the PHS
Policy on Humane Care and Use of Laboratory Animals, applicable USDA
regulations and the Institution\'s policies governing the use of
vertebrate animals for research, testing, teaching or demonstration
purposes. Signature further certifies that the investigator will
continue to conduct the project in full compliance with the
aforementioned requirements.

  ---------------------------------------------------------------------------------------- ------------------------------------------------------------------------------
  **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**   **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

  Signature of the Principal Investigator                                                  Date
  ---------------------------------------------------------------------------------------- ------------------------------------------------------------------------------

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--
\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

Section 1 would be completed by the IACUC Office via database generation
of the report form. The information captured in this section is
considered to be basic protocol-identifying data, which may be helpful
to any designated reviewer, as well as to the Committee, in their
assessment. In addition, certain items, such as the pain category and
nature of the protocol may prompt the IACUC to look more closely at the
continuing review update.

Item 4\--Protocol Status; 5\--Funding Status; and 6\--Project Personnel.
The status of the protocol, funding source, and changes in project
personnel are fairly standard questions to which the investigator is
expected to provide responses.

Item 7\--Progress Report. The progress in achieving the specific aims of
the protocol should be described. The information in this section should
be provided as an update to help the IACUC document the continued
approvability of the research. For example, if 50 dogs were used and the
investigator had no progress to report, in light of the specific aims of
the protocol, it would be reasonable for the IACUC to request
clarification. It should, however, be recognized that scientific inquiry
may involve \"blind alleys\", and failed experiments, thus resulting in
little progress in the short- versus long-term.

Item 8\--Problems/Adverse Events. Any unanticipated problems or adverse
events that have occurred should be reported, as well as an explanation
of how these events/problems were resolved. Depending on the information
provided here, this response may also need to be factored into the
IACUC\'s assessment of the ethical cost-benefit justification.

Item 9\--Alternatives to Animal Use. This section raises the question of
whether any viable alternatives to use of live animals have become
available since the last IACUC review.

Item 10\--Alternatives to Potentially Painful Procedures. This section
asks whether there are any alternatives to USDA Category D or E
procedures that are potentially less painful and could be used to
achieve any of the specific aims of the research. The USDA Category D
and E procedures are defined as follows. Animal activities in Category D
involve \"procedures that may cause more than momentary or slight pain
or distress\" for which appropriate sedatives, analgesics, or
anesthetics will be administered (12,13). Category E is similarly
defined, with the exception that sedatives, analgesics, or anesthetics
cannot/will not be administered due to scientific
considerations/requirements (13).

Item 11\--Duplication. This section requests assurance that the animal
activities do not unnecessarily duplicate previous experiments, as
required by USDA regulations.

Item 12\--Future Plans. The investigator is asked to indicate future
plans for continuation of his/her project. This would include an
indication as to whether the research would continue as originally
approved; or conversely, if changes are planned, an outline,
description, and brief justification of the proposed changes should be
provided.

Finally, the investigator is asked to sign the Continuing Review Form,
which contains a certification of his/her understanding and
responsibility for conduct of animal activities in accordance with the
PHS Policy, USDA regulations and the institution\'s (IACUC) policies.
Signature here also attests to the accuracy of the investigator\'s
responses. Requiring completion of this form, at least annually,
indicates to the investigator the seriousness of the IACUC\'s review and
the importance of investigator accountability for his/her research
activity; for reporting it accurately; and for justifying continuance of
the research project for another year. Accordingly, the IACUC, through
its designated reviewer mechanism, is also held accountable for
appropriate and responsible review of the IACUC protocol file, and for
continuation approval of ongoing animal research, if it is still
justified.

**Method of IACUC continuing review.** All IACUC members would be
provided a copy of the completed Continuing Review Form, and would have
access to the corresponding IACUC protocol file on request. Any IACUC
member could ask for a full committee review of the Continuing Review
Form and the protocol. Utilizing the \"designated reviewer\" process, if
none of the IACUC members requests full committee review, the IACUC
Chair would then designate at least one qualified member (i.e.,
designated reviewer) to conduct an in-depth review of the current
protocol in conjunction with the Continuing Review Form. This review
would include consideration of the previously described continuing
review criteria in accordance with PHS Policy IV.C. The designated
reviewer would then review and be authorized to approve, require
modifications in order to approve, or require full committee review of
the protocol in question. By conducting such a comprehensive \"de novo\"
review on an annual basis, using this model, there is no further PHS
Policy requirement for continuing review at three-year intervals.

The way in which an institution chooses to implement the PHS Policy and
USDA regulations is subject to change over time. Changes in IACUC
membership may result in different perceptions and judgments regarding
animal use issues. These changes may affect the outcome of continuing
review, as will the evolutionary changes in protocol review forms, new
regulations and guidelines, and precedents set by ongoing regulatory
compliance activities, internal and external to the institution. Oki and
Prentice, therefore, recommend that, in addition to the procedures
outlined previously, a complete new IACUC protocol review form (i.e.,
new IACUC application form) be submitted if a project will extend beyond
six years. There is, however, no federal requirement for resubmission of
a new application for IACUC review within any time frame.

In summary, the review process and report form described in this section
meet the requirements of the PHS Policy and the USDA regulations for
continuing review. Use of this model for performing IACUC continuing
review would rely upon yearly comprehensive \"de novo\" reviews for
institutions desiring to comply with both sets of requirements (PHS
Policy and USDA regulations).

**DISCUSSION**

The PHS Policy and USDA regulations were intentionally written to avoid
a great deal of specificity with regard to institutional procedures.
This has provided institutions with a needed degree of flexibility in
designing, implementing and adjusting their own individual systems of
ensuring compliance with the PHS Policy and the USDA regulations. Many
provisions of the PHS Policy and USDA regulations are, therefore, open
to variable methods of implementation. Over the last decade,
academicians, administrators and federal regulators have struggled with
the imperative to interpret and apply the PHS Policy and USDA
regulations in a practical, meaningful and reasonable way to ensure the
highest possible standards of laboratory animal welfare while
facilitating valuable research for the benefit of humans and/or animals.
As a result, our understanding of what constitutes appropriate animal
welfare in a research context has grown tremendously. Today, the IACUC
is a far more sophisticated and effective review body than it was in
1985 when the PHS Policy was first promulgated.

It is not surprising that there has not always been agreement between
the academic/research community and federal regulators. Some have
publicly criticized the OPRR and the USDA for failing to provide \"black
and white\" guidance on exactly how the PHS Policy and USDA regulations
should be interpreted and implemented. In response, however, it is our
contention that laboratory animal welfare is best promoted by engaging
in a partnership of communication and problem solving between the
federal regulators of animal welfare, the IACUCs, and the investigators
who use animals in research and other activities. In addition, the
philosophy and message of animal welfare groups who oppose animal-based
research should be given thoughtful consideration as we struggle to
achieve the appropriate balance between the needs of science and
fulfillment of our moral and ethical responsibility to animals and
society. Our joint and mutually accepted understanding of the meaning of
the \"letter\" and the \"spirit\" of the PHS Policy and USDA regulations
has evolved and continues to do so in the interest of promoting animal
welfare and facilitating valuable research.

**CONCLUSIONS**

The model for continuing review presented in this paper represents a
comprehensive approach and should not be confused with a minimalist\'s
approach to the task (i.e., compliance with only the \"letter of the
law\" without attempting to address \"the spirit of the law\"). To
achieve the highest possible standards of laboratory animal welfare,
institutions should view the PHS Policy and USDA regulations as
establishing standards that serve as a platform on which to build as our
understanding of science, animal welfare and research ethics increases.
We think the institution\'s animal care and use program should be
dynamic and evolving in nature as we identify ways in which laboratory
animal welfare can be improved. It is important to note that although
the model described herein by Oki and Prentice was designed principally
to meet PHS requirements for triennial review, it also complies with
and, indeed, exceeds the USDA requirements for annual review. Finally,
we point out that institutions may adopt other models for performing
continuing review that may be equally acceptable from regulatory and
ethical viewpoints.

**REFERENCES**

\_ National Institutes of Health, 1986. Public Health Service Policy on
Humane Care and Use of Laboratory Animals.

\_ Code of Federal Regulations, 1989. Title 9, Parts 1, 2, and 3, Animal
Welfare Final Rules, Federal Register, 54 (168): 36112 - 36163.

\_ National Institutes of Health, 1986. Public Health Service Policy on
Humane Care and Use of Laboratory Animals, p. 8.

\_ Code of Federal Regulations, 1989. Title 9, Parts 1, 2, and 3, Animal
Welfare Final Rules, Federal Register, 54 (168): 36153.

\_ Office for Protection from Research Risks, Division of Animal
Welfare, 1991. Issues for Institutional Animal Care and Use Committees
(IACUCs): \"The PHS Responds to Commonly Asked Questions\", ILAR News,
33 (4): 68-70.

\_ Office for Protection from Research Risks, Division of Animal
Welfare, 1993. Issues for Institutional Animal Care and Use Committees
(IACUCs): \"Frequently Asked Questions About the Public Health Service
Policy on Humane Care and Use of Laboratory Animals\", ILAR News, 35
(3-4): 47-49.

\_ National Institutes of Health, 1992. ARENA/OPRR Institutional Animal
Care and Use Committee Guidebook. NIH Publication No. 92-3415, p. A-3.

\_ Code of Federal Regulations, 1989. Title 9, Parts 1, 2, and 3, Animal
Welfare Final Rules, Federal Register, 54 (168): 36133.

\_ Singleton, R., Jr., 1994. \"Wither Goest Vivisection? Legislative and
Regulatory Perspectives\", Pers. Biol. Med., 38: 41-57.

\_ Prentice, E.D., Crouse, D.A., and Mann, M.D., 1992. Scientific Merit
Review: The Role of the IACUC. ILAR News, 34 (1-2): 15-19.

\_ Prentice, E.D., Crouse, D.A., and Rings, R.W., 1990. Approaches to
Increasing the Ethical Consistency of Prior Review of Animal Research.
Invest. Radiol., 25(3): 271-274.

\_ Code of Federal Regulations, 1989. Title 9, Parts 1, 2, and 3, Animal
Welfare Final Rules, Federal Register, 54 (168): 36152.

\_ United States Department of Agriculture, 1991. APHIS Form 7023,
Interagency Report Control No. 0180-DOA-AN.

![](media/image1.wmf){width="6.55in" height="6.25e-2in"}

**ILAR Journal. 1995**; 37(4):190‑192. Use of Electronic Communications
for IACUC Functions

\[Nelson Garnett, D.V.M. is Director, Division of Animal Welfare, Office
for Protection from Research Risks, National Institutes of Health.
Stephen Potkay, V.M.D. is Chief, Compliance Branch, Division of Animal
Welfare, Office for Protection from Research Risks, National Institute
of Health.\]

**INTRODUCTION**

The Public Health Service (PHS) Policy on Humane Care and Use of
Laboratory Animals (Policy) describes eight basic Institutional Animal
Care and Use Committee (IACUC) functions (PHS 1986, IV.B.1. - 8.). These
functions vary in complexity and include reviewing the overall animal
program and inspecting the animal facilities every 6 months; reviewing
and approving animal study proposals initially and at least once every 3
years thereafter (annually under U.S. Department of Agriculture Animal
Welfare regulations \[9 CFR 1-3\]); reviewing concerns about the animal
care and use program; making recommendations to the institutional
official about any aspect of the institution\'s programs, facilities, or
training; and suspending activities involving animals under certain
circumstances.

Traditionally, these activities have been accomplished through meetings
physically attended by members of the IACUC. The traditional meeting
provides the kind of environment which is most conducive to thoughtful
deliberation and interaction and is still regarded as the optimum forum
for many of the IACUC functions.

With the advent of technological advances in communication capabilities,
however, questions have arisen about the acceptability of using
telephone conference calls, audio-visual conferencing, facsimile
transmission (fax), and electronic mail (e-mail) as well as postal mail,
in lieu of face-to-face meetings for the conduct of IACUC business.

Because of the diversity of activities that IACUCs are called upon to
engage in, it is not possible to anticipate every situation in which
each alternative to a traditional meeting may be applicable.
Nevertheless, the Office for Protection from Research Risks (OPRR) of
the PHS considers that there may be circumstances in which one or more
of the foregoing options may be used. A discussion of several such
circumstances, grouped by categories, is as follows:

**GENERAL ISSUES**

*Animal Welfare Assurance*

The Animal Welfare Assurance (Assurance) on file with OPRR must contain
a description of the procedures that the IACUC will follow to fulfill
the requirements of the PHS Policy. OPRR expects that all approved
Assurances are complete and accurate and that they reflect the use of
any nontraditional procedures for conducting IACUC business.

*Distribution of Information*

The conveyance, by fax or e-mail, of information such as the
institutional Assurance; animal study proposals; agendas and minutes of
meetings; institutional policies and standard operating procedures;
reports, announcements or correspondence from oversight or regulatory
agencies; and other matters related to the institutional animal care and
use program for consideration and review by IACUC members would be
regarded as appropriate.

A \"convened quorum\" generally means a meeting of more than 50 percent
of the members of a group, that is, the minimum number necessary to
conduct official business. As a standard operating procedure, this
should be the traditional gathering of people in a meeting room at the
same time. Other forums that provide the same opportunities for members
to deliberate interactively with a quorum of other members of the
committee may be functionally equivalent. Conference calls, audio-video
conferences, and possibly some forms of highly interactive on-line
computer discussion groups may qualify in exceptional circumstances.

As an operating standard, the conduct of IACUC meetings should allow
greater opportunity for members to interact than is permitted by simple
fax or e-mail messages. However, in exceptional circumstances, telephone
and audio-visual conferencing may be appropriate alternatives to
face-to-face meetings. To be considered a valid IACUC meeting, all
members must be given ample prior notice to participate, and at least a
quorum of the voting members must be convened on the same conferencing
(telephone or audio-visual) line. In addition, the quorum of IACUC
members must be in direct communication with each other and be given
full opportunity to participate for the duration of the meeting. In
either case, minutes of the meetings must be compiled and maintained on
file as required by oversight and regulatory agencies.

IACUC meetings at which voting occurs warrant special consideration.
While telephone conferencing and audio-visual conferencing may be
appropriate alternatives to face-to-face meetings in exceptional
circumstances, members must be given ample prior notice to participate
and be provided in advance with the materials or information on which
they will vote. The meeting must consist of at least a quorum of the
voting members convened on the selected telephone or audio-visual
network who are in direct communication with each other and given a
genuine opportunity for deliberation and interaction for the duration of
the meeting. It is especially important to note that using individual
one-on-one meetings, the telephone, fax, or e-mail to poll or otherwise
obtain members\' votes outside of a convened quorum does not meet PHS
Policy requirements. As with other IACUC functions, documentation must
be compiled and kept on file in accordance with oversight and regulatory
agencies.

*Polling*

Polling is defined as sequential, one-on-one communication, either in
person or via telephone, e-mail, fax, U.S. mail, or by other similar
means. Polling is an appropriate mechanism for providing all committee
members with the opportunity to call for full review of a protocol prior
to initiating the \"designated reviewer\" method of protocol review
described below. It may also be appropriate as a mechanism for
distributing and reviewing drafts of meeting minutes or reports.

The simple polling of IACUC members does not, however, satisfy the
definition of a meeting of a convened quorum and should not be used for
conducting IACUC business that requires the vote of a convened quorum of
the committee. For example, polling should not be considered a valid
method of voting under the \"full committee\" review method of protocol
review and is not an acceptable substitute for having a vote of a
convened quorum on the suspension of a previously approved activity
involving animals.

*Security*

Institutions utilizing innovative modes of communication must be aware
of the potential security problems inherent in the method chosen. Some
material considered by IACUCs should be treated as privileged or
confidential, especially prior to final committee action. In the case of
trade secrets, such information may be protected by law (7 USC 2157,
section 27). Because of widespread reports of unauthorized access to
computer records, the use of available computer security measures such
as passwords, controlled access, and encryption should be considered.

*Signatures*

Many IACUC activities involve the need for documenting votes or
verifying committee approval. Letters and reports often require
signatures in order to be legally binding. Techniques for providing such
legally acceptable \"electronic signatures\" are being developed by the
computer industry to address this problem. Currently, electronic
communication is frequently used to facilitate the rapid conduct of
business with signed original documents to follow for the permanent
record.

**PROTOCOL REVIEW**

Both the PHS Policy and the USDA regulations recognize 2 methods of
protocol review. Although institutions frequently introduce procedural
variations and assign different names to their processes, all protocol
review must be consistent with one of the following prescribed methods:

*Full Committee Review*

Full committee review requires a meeting of a convened quorum of the
IACUC. As outlined in the definition of convened quorum, full committee
review is an example of an IACUC function that requires committee
deliberation, interactivity, and voting, and which could be
accomplished, in exceptional circumstances, through a carefully devised
mechanism using telephone conferencing, audio-visual conferencing, or
some other form of highly interactive electronic communication.

*Designated Member Review*

The other recognized procedure for protocol review is called designated
member review. In this method, prior to review, all members are provided
with the necessary information concerning the proposed research
projects. All members are then given the opportunity to request full
committee review. If no member calls for full committee review, then the
IACUC Chair may designate one or more qualified IACUC members to review
proposed research projects and to have authority to approve, require
modifications in (to secure approval), or request full committee review
of those research projects.

Polling is an acceptable mechanism for providing all IACUC members with
the *prior opportunity* to call for full review. It should be noted that
the polling of IACUC members in this instance is not an approval vote on
the proposed research. Records of such polling, however, are useful to
document that the opportunity for members to call for full committee
review has been provided.

**SUSPENSION OF AN ACTIVITY**

The PHS Policy and USDA regulations prescribe procedures that must be
followed in order to suspend a previously approved activity. Such action
requires a review of the matter at a convened quorum of the IACUC and a
suspension vote by a majority of the quorum present. Innovative
mechanisms that meet the description of convened quorum could be used to
perform this IACUC function.

**REPORTING**

All official IACUC reports are considered to be the result of \"full
committee\" action. Thus, endorsement of final reports issued under the
IACUC aegis should include the opportunity for full participation and
the opportunity for minority views to be expressed and recorded. This
function should normally occur at a meeting of a convened quorum of the
IACUC. Alternate methods of achieving a convened quorum may also be
applicable to this IACUC function.

**SEMIANNUAL REVIEW AND INSPECTION**

Semiannual program review and facility inspection may be conducted in a
variety of ways, as described in the PHS Policy and USDA regulations.
However, final reports must be reviewed and endorsed by a convened
quorum as described above.

**SUMMARY**

The PHS Policy concept of institutional self-regulation with local IACUC
oversight evolved from similar mechanisms applied to the protection of
human subjects in research. As with the Institutional Review Board (IRB)
for human subjects, assumptions regarding the general environment in
which oversight of animal related research takes place were included in
the design of prescribed oversight mechanisms. One of those assumptions
was that committees normally function through periodic meetings where
members would consider, deliberate, and vote on matters within their
purview. This model did not anticipate the technological advances that
would make it possible to approximate the traditional meeting
environment from greater distances and with greater ease and speed than
was the norm at that time.

Although the traditional meeting is still seen as the optimum
environment for fulfilling the intent of the PHS Policy, OPRR recognizes
the new communications tools available and the need for flexibility in
the ways that institutions may comply with the PHS Policy in the many
diverse settings encountered. For these reasons, several criteria have
been provided for establishing alternate methods that may be considered
functionally equivalent to meetings of a convened quorum under
exceptional circumstances. Two of those criteria are that the alternate
approach must include a high degree of interactivity and allow for
careful deliberation of sensitive issues. Another is that a quorum of
IACUC members must be in direct communication with each other and be
given full opportunity to participate for the duration of the meeting.
Institutions are reminded that details of their IACUC procedures,
especially those that may vary from those outlined in the PHS Policy,
should be thoroughly described in the institutional Assurance and
submitted for OPRR review.

**REFERENCES**

Animal Welfare Act of 1966 (P.L. 89-544) inclusive of amendments; 1970
P.L. 91-579); 1976 (P.L. 94-279); 1985 (P.L. 99-198).

Animal Welfare Regulations. Code of Federal Regulations, Title 9
(Animals and Animal Subproducts), Subchapter A (Animal Welfare), Parts
1-3 (9 CFR 1-3). (Available from Regulatory Enforcement and Animal Care,
U.S. Department of Agriculture, 4700 River Road, Room 2D01, Riverdale,
MD 20737)

Public Health Service (PHS). 1986. Public Health Service Policy on
Humane Care and Use of Laboratory Animals. Washington, D.C.: U.S.
Department of Health and Human Services. (Available from: Office for
Protection from Research Risks, 6100 Executive Blvd., MSC 7507,
Rockville, MD 20892-7507. Tel: 301/496-7163; Fax: 301/402-2803.)

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**Lab Animal. 1995**; 24(9):24‑26. FAQs about the PHS Policy on Humane
Care and Use of Laboratory Animals

Feature Article by Stephen Potkay, VMD, Nelson L. Garnett, DVM, John G.
Miller, DVM, Cynthia L. Pond, DVM, MS, and Denis J. Doyle

\[The article was prepared by staff members of the Division of Animal
Welfare, Office for Protection from Research Risks, National Institutes
of Health, 6100 Executive Boulevard, Suite 3B01, MSC 7507, Rockville, MD
20892-7507. Send reprint requests to Stephen Potkay at the address
listed above.\]

The Office for Protection from Research Risks (OPRR) of the National
Institutes of Health (NIH) develops, implements, and oversees compliance
with the Public Health Service (PHS) Policy on Humane Care and Use of
Laboratory Animals (Policy).^1^ The PHS Policy and the U.S. Department
of Agriculture\'s (USDA) Animal Welfare Regulations,^2^ are the two
principal federal documents that set forth requirements for animal care
and use by institutions using animals in research, testing, and
education. One of OPRR\'s primary functions is to assist institutions in
implementing PHS Policy by responding to policy-related questions
^3,\ 4^. The following represent several frequently asked questions from
institutions and the OPRR responses:

*1. The Institutional Animal Care and Use Committee (IACUC) at our
institution is uncertain about what criteria to use in determining what
constitutes a \"significant change\" to an approved research protocol,
so that it can implement the appropriate review mechanism. How should we
interpret the PHS Policy in this regard?*

Owing to the great diversity of research performed at assured
institutions, it is not possible for this Office to anticipate all of
the changes that investigators might potentially make to approved
protocols and provide an exhaustive listing of those considered
significant. However, institutions have requested OPRR to evaluate a
variety of situations in which the significance of protocol changes was
a primary concern. As a result, we have identified several kinds of
significant changes that may serve as examples to guide the IACUC in its
determinations. They include but are not limited to: changes in the
objectives of a study; proposals to switch from nonsurvival to survival
surgery; changes in the degree of invasiveness of a procedure or
discomfort to an animal; changes in species or in the approximate number
of animals used; changes in personnel involved in animal procedures; and
changes in anesthetic agent(s), the use or withholding of analgesics,
and methods of euthanasia. Additional factors may involve changes in the
duration, frequency, or number of procedures performed on an animal.
Based on these considerations, IACUCs should develop guidelines to
follow at their institution and ensure they inform each principal
investigator. It must become institutional policy that no one may
implement changes categorized as significant prior to IACUC review and
approval.

*2. Our institution purchases antibodies from commercial sources for use
in various PHS-supported studies conducted in its facilities. Does the
PHS Policy require that the commercial source have an Animal Welfare
Assurance on file with the OPRR?*

In the case that standard reagent antibodies (*e.g.* mouse-antihuman)
are produced by a commercial supplier using their own resources and
offering them for general sale, for example, through a catalogue, the
institution may consider the antibodies to be \"off-the-shelf\"
reagents, and the supplier is not required to file an Assurance with
OPRR. If, on the other hand, a supplier or contractor produces custom
antibodies using antigen(s) provided by or at the request of a principal
investigator, the antibodies are considered \"customized\" and the
vendor or subcontractor must file an Assurance with OPRR.

Usually it is known in advance that someone intends to perform this kind
of work under a PHS grant. In such cases, the applicant must mark the
PHS Grant Application (PHS Form 398) \"yes\" for vertebrate animal
involvement and include the appropriate Animal Welfare Assurance
number(s), verification of project-specific date of IACUC protocol
review, and the identification of all project performance sites. All
animal-related activities supported by the PHS must be conducted at
Assured institutions and must be reviewed and approved by an IACUC. When
both the PHS Grantee and its Contractor hold OPRR-approved Assurances,
some latitude is allowed in determining which IACUC (if not both) will
review the proposal. However, the institution which subcontracts or
subgrants any animal activity retains partial accountability for
providing effective oversight mechanisms to ensure compliance with the
PHS Policy. Part of that responsibility includes ensuring that
subgranted/subcontracted animal-related activities are conducted only at
an Assured institution.

*3. How extensive must the animal care and use training program be in
our small institution, and at what frequency should it be offered?*

Each Assured Institution is responsible for training its staff to meet
the performance requirements cited in paragraph IV.C.1.a.- g. of the PHS
Policy, and guidelines have been developed to assist institutions to
meet these objectives. ^5,\ 6^ OPRR recognizes research programs vary
from one institution to another, and are relative to the size and nature
of the institution, staffing, numbers of species and individual animals
maintained, and the kinds of research conducted. Therefore, the scope
and depth of instructional programs and the frequency at which they are
offered will also vary. At a minimum, however, the Policy requires
institutions to ensure that individuals who use or provide care for
animals are trained and qualified in the appropriate, species-specific
housing methods, husbandry procedures, and handling techniques. The
institution must ensure that research staff members performing
experimental manipulation, including anesthesia and surgery, are
qualified through training or experience to accomplish such procedures
humanely and in a scientifically acceptable fashion. They must also
provide training or instruction in research and testing methods that
minimize the number of animals required to obtain valid results and
minimize animal distress. Institutions must also ensure that
professional staff whose work involves hazardous biological, chemical,
or physical agents have training or experience to assess potential
dangers and select and oversee the implementation of appropriate
safeguards. Finally, OPRR strongly recommends that institutions offer
their staff access to training leading to certification in animal
technology such as that available from AALAS or a formally designated
academic program. Institutions should also know and ensure compliance
with any initial and continuing education State requirements for the
licensing of veterinary or animal health technicians.

*4. In the event that our IACUC reports a serious noncompliance with the
PHS Policy or deviation from the **Guide**, we understand that the
report must fully explain the circumstances and actions taken to correct
the situation. How soon after the noncompliance or deviation is
identified must we submit the report? How closely is our institution
held to meeting its self-imposed schedule for correction?*

The PHS Policy requires institutions report promptly any serious or
continuing noncompliance with the Policy or serious deviation from the
provisions of the *Guide*. Examples of noncompliance and deviations
include: conducting an animal-related activity without appropriate IACUC
review and approval; the temporary or permanent interruption of an
activity involving animals by the IACUC; and conditions that jeopardize
the health or well-being of an animal. The USDA\'s Animal Welfare
Regulations are more specific, requiring institutions report such
matters to the Animal Plant and Health Inspection Service (APHIS) and
the funding agency if not resolved within 15 business days of the
completion date specified in the IACUC\'s initial corrective plan and
schedule. The IACUC should use the interval to investigate and develop a
definitive corrective plan and a schedule for implementation. In many
cases, it also provides ample opportunity for total resolution of the
problem. One should note, however, that solution of the problem does not
dismiss the institution\'s obligation to file a report with OPRR and
APHIS. When the IACUC cannot completely resolve the noncompliance or
deviation within the allotted time, the institution must present a
specific and reasonable corrective plan and schedule. If the situation
directly involves animals and threatens their health and safety, such
plans are to contain interim measures, including possible relocation of
the animals at risk. OPRR\'s acceptance of a plan and schedule is
usually conditioned on notification when the corrective action is
complete. It is recognized that circumstances which are beyond the
institution\'s control may arise and prevent the scheduled completion of
the plan. In such cases, OPRR will consider requests to extend the
schedule if the circumstances are adequately described and the proposed
new deadline is reasonable.

*5. Our institution receives funding from PHS and non-PHS sources. Must
we include those programs, projects, and facilities which are not
supported by the PHS in our Assurance of Compliance?*

OPRR advises institutions that the maintenance of uniform and consistent
standards is an essential ingredient in the development and
implementation of a quality animal care and use program. Only when an
institution can document that the animal care and use program funded by
a non-PHS source is entirely separate and distinct, physically and
programmatically, from PHS-supported activities will OPRR consider its
exclusion from the Institutional Assurance. Unless there is such total
separation, OPRR cannot accept the potential risks presented to animals
involved in PHS-funded research. Institutions should also keep in mind
the public perception that institutions not wishing to conduct portions
of their animal research programs in accordance with the Policy may be
applying a double standard of animal care to the detriment of overall
animal health and well-being.

*6. Our institution uses animals as sentinels in the animal disease
surveillance program, in breeding programs, and as donors for blood and
blood products. Since these animals are not used in research per se, is
it necessary to develop protocols for the review and approval of our
IACUC?*

PHS Policy applicability is not limited to research. It also includes
all activities involving animals including testing and teaching. OPRR
has determined that although animals used as sentinels, breeding stock,
chronic donors of blood and blood products, or for other similar
objectives may not be part of specific research protocols, their use for
these purposes contributes significantly to the institutional research
program and constitutes activities involving animals. Consequently, the
IACUC must receive and approve of protocols and appropriate systems to
monitor the use of animals prior to the commencement of such activities,
and should then perform reviews at the appropriate intervals (IV.C. of
the PHS Policy).

*7. Could you describe the kind and extent of the employee health
program required by the PHS Policy?*

Principal requirements for an institutional occupational health program
are outlined in the **Guide for the Care and Use of Laboratory
Animals**. Institutional research programs vary regarding the animal
species used and the potential hazards presented by them. The
biological, chemical, or physical agents employed in the course of the
research likewise vary. Thus, the institution must base their health
program on an assessment of the risks present in its particular animal
research program, including those in cage washing and other support
activities. Basic elements of any health program, however, should
provide: a pre-employment medical evaluation and history; immunization
against tetanus; detailed training on how to perform required procedures
safely; instruction in personal hygiene, zoonoses, and precautions for
pregnant women and others at risk; protective clothing and devices;
instruction in first aid procedures appropriate to potential hazards;
and access to medical attention for the treatment of animal bites,
scratches, allergies and other job-related injuries or illnesses. When
there is risk of exposure to rabies through the use of random-source
dogs and cats and certain wildlife species, the institution should offer
preexposure immunization, and should regularly schedule tuberculin
testing for all personnel exposed to nonhuman primates. The institution
should have precautions in place and a zoonoses surveillance mechanism
established when work involves exposure to nonhuman primates and species
likely to harbor the causative agents of diseases such as Q fever,
tularemia, hantavirus pulmonary syndrome, and plague. When research
involves infectious diseases, such as hepatitis B, for which there are
safe and effective vaccines, the use of prophylactic immunizations
should also be considered. A health program is required not only for
persons having \"frequent contact with animals,\" but for all
\"personnel who work in laboratory animal facilities.\" These include
not only animal caretakers, technicians, students, volunteers,
investigators, and veterinarians but facilities maintenance engineers,
housekeepers, security, and other staff. OPRR recommends that the
foregoing phrases be interpreted in the context of the potential risks
to which the persons are exposed. For example, those working full time
in closed, pathogen-free rodent colonies where no hazardous agents are
employed are at considerably less risk than individuals exposed for
brief periods to nonhuman primates, random source dogs and cats, or to
hazardous biological, chemical, or physical agents. Each institution\'s
risk assessment and the implementation of its health program should rely
heavily on input from persons knowledgeable in occupational safety and
health, biosafety, and radiation safety, and include both preventive as
well as diagnostic and treatment features.

Received 8/18/95; accepted 9/7/95

References

1\. Public Health Service (PHS). Public Health Service Policy on Humane
Care and Use of Laboratory Animals. US Department of Health and Human
Services. (Available from: National Institutes of Health, Office for
Protection from Research Risks, 6100 Executive Boulevard, Suite 3B01,
MSC 7507, Rockville, MD 20892-7507) Washington, DC, 1986.

2\. Animal Welfare Regulations. Code of Federal Regulations, Title 9
(Animals and Animal Subproducts), Subchapter A (Animal Welfare), Parts
1-3 (9 CFR 1-3). (Available from Regulatory Enforcement and Animal Care,
U.S. Department of Agriculture, Unit 84, 4700 River Road, Riverdale, MD,
20737).

3\. Division of Animal Welfare, Office for Protection from Research
Risks. The Public Health Service Responds to Commonly Asked Questions.
*ILAR News* **33:**68-70, 1991.

4\. Division of Animal Welfare, Office for Protection from Research
Risks. Frequently Asked Questions about the Public Health Service Policy
on Care and Use of Laboratory Animals. *ILAR News* **35:**47-49, 1993.

5\. *Education and Training in the Care and Use of Laboratory Animals: A
Guide for Developing Institutional Programs*. Committee on Educational
Programs in Laboratory Animal Science, ILAR, Commission on Life
Sciences, National Research Council. Washington: National Academy Press,
Washington, DC, 1991.

6\. Bennett BT, Brown MJ, Schofield. *Essentials for Animal Research: a
primer for research personnel*, 2nd Ed. 1994. AWIC, National
Agricultural Library, Beltsville, MD, 1994.

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**Lab Animal. 1994**; 23(8):28‑29. Compliance at the Institutional Level

*By Axel V. Wolff, MS, DVM and Paul D. Smith PhD*

\[At the time this article was published the authors, Axel V. Wolff, MS,
DVM and Paul D. Smith PhD, were affiliated with the NIH National Center
for Research Resources. Axel Wolff is now Senior Assurance Officer,
Division of Assurances, Office of Laboratory Animal Welfare, NIH.\]

Although this commentary focuses on institutions funded through the
Public Health Service (PHS), it is generally applicable to all
institutions because PHS policy requires institutions to comply with the
Animal Welfare Act and other Federal statutes and regulations relating
to animals. The PHS policy does not affect those state or local laws or
regulations which impose more stringent standards for the care and use
of laboratory animals. Animal facilities not supported by the PHS come
under USDA jurisdiction, follow the regulations outlined in the Animal
Welfare Act, and are administered thorough the Animal and Plant Health
Inspection Service (APHIS) via the Regulatory Enforcement and Animal
Care Unit (REAC).

Institutions achieve compliance through the assurance statement filed
with The Office for Protection from Research Risks (OPRR). OPRR is
responsible for implementation and interpretation of PHS Policy,
negotiating Animal Welfare assurances, and evaluating compliance. The
Institutional Animal Care and Use Committee (IACUC) performs a critical
element of assuring compliance by evaluating, at least semi-annually,
the institution's animal program and the facilities used in supporting
the research. The evaluation must describe the institution's adherence
to the *Guide for the Care and Use of Laboratory Animals (Guide),*
identify and provide reasons for any departures from the *Guide,*
distinguish significant *(i.e.,* one that may be a threat to the health
or safety of the animal) and minor deficiencies, and provide a plan and
schedule for correcting the deficiencies. The report is submitted to the
institutional official responsible for implementing the provisions of
the Animal Welfare Act and PHS Policy.

The IACUC may not exclude any member from participating in any aspect of
an evaluation, and it may use subcommittees of no less than two members.
The report must be signed by a majority of the members and must include
any minority views. The IACUC must address such issues as: the
institution's commitment to supporting an accreditable animal program;
the organizational structure and staff in place to support the research;
the mechanisms in place for addressing the human health needs of the
employees; the training programs available to scientists, animal
technicians, and other personnel involved with animal care, treatment,
and use; the procedures established for routine daily operations; the
mechanisms available for reporting irregularities; and other aspects of
the animal program. All facilities used for holding animals and all
animal procedure space must be inspected for compliance with the
standards established in the *Guide,* PHS policy, and the Animal Welfare
Act. The report must include a reasonable and specific plan and schedule
with dates for correcting any deficiency. If the institution fails to
adhere to the plan and schedule, the IACUC must report in writing within
15 business days through the institutional official to OPRR and any
federal agency funding that activity.

The IACUC is authorized to suspend any activity involving animals if it
determines that the activity is not being conducted in accordance with
the previously approved animal study proposal, provisions of the Animal
Welfare Act, PHS Policy, the *Guide,* or the institution's assurance.
Usually, the IACUC will initiate suspension of an activity and report
through the institutional official to OPRR.

**Program Compliance**

The Animal Study Proposal (ASP) is the first official step a principal
investigator takes to initiate an animal study, and it is usually the
first interaction with the IACUC. Reviewing ASPs is one of the IACUC's
mandates, and it allows assurance of numerous compliance issues such as
humane animal use, suitability of facilities, training qualifications,
*etc.* We will discuss the items which a typical ASP should address
using the standard NIH form *(see* reference NIH 3040-2).

The first section deals with administrative data that encompasses
information such as the principal investigator's name, address, title of
the project, and names of all individuals who will be conducting animal
procedures. The animal requirements (species, sex, numbers of animals to
be used) follow, allowing inquiry into one of the three Rs, reduction in
the number of animals used in research.

The next section deals with transportation of animals, and if deliveries
from commercial vendors are involved, the IACUC can assess Animal
Welfare Act shipping regulation compliance. In the section outlining
study objectives, the investigator explains the purpose of the study and
the necessity for animal use. The other Rs - refinement and
replacement - can be addressed here. A description of the experimental
design and the actual procedures performed follows, and is probably the
most important description used by the IACUC to assess actual care and
use. The investigator must address very specific issues including: what
types of inoculations are given; how animals are restrained; whether the
animal will experience pain or discomfort; and the experimental
end-point. In this vein, the next section specifically addresses the
details of survival surgery and ascertains the surgeon's qualifications,
adherence to the *Guide,* and the performance of multiple major
procedures.

In a separate category, the investigator must again address pain or
distress by placing study animals in the USDA pain categories 8 '
minimal or no pain, D ' pain relieved by appropriate measures, E '
unrelieved pain) and give the numbers of animals in each column over the
course of the year. This information is specifically reported to USDA in
the yearly report, and at this point the principal investigator attaches
additional justification for any Column E studies.

The next section covers in detail the types and amounts of anesthetics,
analgesics, and tranquilizers used during the course of the study to
alleviate pain and distress. The veterinary representative on the IACUC
can determine appropriateness of the drug for the species studied. A
separate section deals with euthanasia, and comparison with the most
recent AVMA Panel on Euthanasia guidelines determines the
appropriateness of the method.

The investigator addresses compliance with related non-animal
regulations in the hazardous agent or biosafety section. Here, questions
regarding radioisotopes, biohazards, dangerous chemicals or drugs,
recombinant DNA, and biosafety level are examined. The institutional
safety official determines the application of the various guidelines for
these agents to the study. Another small section addresses the question
of passing biological material through rodent species and whether rodent
pathogens are present.

Finally, the signatures of the principal investigator, laboratory chief,
IACUC chairperson, and others affirm the institution's commitment to the
provisions of the Animal Welfare Assurance statement and PHS policy. In
this last section, the principal investigator, in accord with PHS
policy: certifies attendance at a training course on animal
investigation and that staff have been adequately trained in animal
handling and use of proper techniques; states that a literature search
was conducted to determine if alternative procedures exist for Column D
and E studies; and, finally, promises to inform the IACUC of any
proposed significant changes in the study.

By means of the ASP document, the IACUC can assess the effect of the
study on the well-being of the research animals and receives assurances
from the investigator that all applicable rules and regulations will be
followed. During review of the document, the IACUC can ask the
investigator questions on any aspects of the proposal. The unique
composition of the IACUC allows it to address veterinary, safety, public
concerns, and research questions. The IACUC ensures compliance by
thorough examination of the proposal prior to approval and subsequent
communication with the investigator after initiation of the work. During
the semi-annual inspection of facilities, the work areas are evaluated,
and every year the ASP is renewed and questions or changes are
expressed. Throughout the course of the study, the IACUC is at liberty
to send a representative to visit the animal research area, and in the
case of a possible infraction any employee, is encouraged to approach
the IACUC with concerns. In this fashion, the IACUC oversees the animal
studies performed at the institution.

*Received 5/17/94; accepted 7/20/94.*

**References *Laws ***Animal Welfare Act 7 USC 2131 *et. seq.* (PL
89-544, August 24, 1966; amended PL 91-579, December 24, 1970; amended
PL 94-279, April 22, 1976; amended PL 99-198, December 23, t985).

The Public Health Services Act as amended by the Health Research
Extension Act, PL 99-158, November 20, 1985 (42 U.S.C. 289d).

***Regulations*** Animal Welfare, 9 CFR, Parts 1,2, and 3.

***Policies*** Public Health Service Policy on Humane care and Use of
Laboratory Animals, September 1986.

*Guide for the Care and Use of laboratory Animals.* NIH Publication No.
85-23. Revised 1985.

US Government Principles for the Utilization and care of Vertebrate
Animals Used in Testing, Research and Training. Federal Register, Vol.
20, No. 97, May 20, 1985.

National Institutes of Health. NIH Policy Manual Chapter 3040-2: Animal
Care and Use in the Intramural Program. Appendix 1 - Animal Study
Proposal.

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**ILAR News. 1993**; 35(3‑4):47‑49. FAQs about the PHS Policy on Humane
Care and Use of Laboratory Animals

Prepared by the staff of the Division of Animal Welfare, Office for
Protection from Research Risks, National Institutes of Health, Bethesda,
Maryland

The Office for Protection from Research Risks (OPRR) of the National
Institutes of Health (NIH) develops, implements, and oversees compliance
with the Public Health Service Policy on Humane Care and Use of
Laboratory Animals (PHS Policy) (PHS, 1986). The PHS Policy and the U.S.
Department of Agriculture\'s (USDA\'s) Animal Welfare Regulations, are
the two principal federal documents setting forth requirements for
animal care and use by institutions using animals in research, testing
and education. One of OPRR\'s primary functions is to assist
institutions in implementing PHS Policy by responding to policy-related
questions.

The following represent several frequently asked questions from
institutions and the OPRR responses:

*1. What standards does the PHS Policy require our institution to follow
in conducting survival rodent surgery, and how do they differ from those
applicable to other species?*

The PHS Policy requires that the recommendations of the *Guide for the
Care and Use of Laboratory Animals* (*Guide*) (NRC, 1985) be adhered to
regarding survival surgical procedures and the environments in which
they are conducted. The *Guide* presents slightly different standards
for rodent and nonrodent species. Briefly, the current requirements are
as follows. Survival surgery may be conducted on rodents in an area that
is used solely for this purpose while the surgery is being performed
(such as a room or a portion of a room). The surgery must be performed
using sterile instruments, surgical gloves, and aseptic procedures
designed to prevent contamination of the operative site. In addition to
the above requirements, survival surgery involving higher vertebrate
species must use aseptic surgical techniques such as wearing sterile
surgical gloves, gowns, caps, face masks; using sterile instruments; and
preparing an aseptic surgical field. Furthermore a separate, dedicated
surgical area, subdivided into a surgical support area, preparation
area, and operating room is mandated. Safeguards against hazards
surrounding the use of explosive gases are required, and anesthesia
scavenging devices or exhaust hoods must be used to eliminate waste
anesthetic gases regardless of the species on which surgery is being
performed.

*2. In the experience of OPRR, what form of administrative organization
works best for directing the animal programs and ensuring compliance
with the PHS Policy?*

It has been OPRR\'s observation that organizations having simple, clear,
direct lines of responsibility and corresponding authority function well
and are better able to respond quickly and effectively to the
requirements of the PHS Policy. The key components in such organizations
are the Institutional Official (IO), the IACUC, and the participating
veterinarian. The IO should have the authority to allocate
organizational resources needed to maintain a smoothly functioning
animal care and use program based on recommendations and advice received
from the IACUC and the veterinarian. The IO should also clearly define
and assign responsibilities and reporting channels for other essential
program elements such as training, occupational health, and maintenance.
The IACUC, appointed by the organization\'s chief executive officer,
usually reports directly to the IO and is empowered to perform its
duties without undue interference. OPRR\'s experience suggests that it
is usually best for the veterinarian also to report directly to the IO
in connection with his or her responsibilities for implementing those
parts of the animal care and use program that are set forth in the PHS
Policy, the Animal Welfare Act (Animal Welfare Act of 1966), and the
*Guide*.

OPRR recognizes that the size and complexity of Assured institutions
vary, and that no single organizational or administrative structure will
be compatible with the needs of all institutions. While the Policy
allows for such institutional flexibility, OPRR strongly recommends that
its organizational channels for implementation be as direct and
straightforward as possible. In OPRR\'s experience, unclear or
inappropriate lines of authority and responsibility have been the
underlying cause for serious cases of programmatic failure.

*3. What is the difference between IACUC animal study proposal review in
a convened meeting and \"expedited\" review, and when is it appropriate
to use the latter?*

Paragraph IV. C. 2. of the PHS Policy and Part 2, Section 2.31 (d)(2) of
the USDA\'s Animal Welfare Regulations require that, as a minimum, all
IACUC members be given for their review a list of proposed research
protocols involving the care and use of animals and that written
descriptions of the projects be available to them. Any member of the
IACUC may then request full review of any protocol by the full
committee. In the absence of such a request, the chairperson may
appropriately designate at least one qualified person to review,
approve, require modifications, or request full committee review.

This process, protocol review by less than the full committee in a
convened meeting, is often referred to as an \"expedited\" review. This
does not correspond, however, to the expedited review process of the
Institutional Review Board applicable to Human Subjects Protection. In
order to comply with the PHS Policy, *no* animal work may begin before
the full committee has either been given the opportunity to review the
protocol and call for a full committee review or before the protocol has
been approved by (1) the majority of a quorum of the members or (2) the
designated reviewer in the absence of a call for full committee review.
In this regard, it should be kept in mind that neither the PHS Policy
nor the Animal Welfare Regulations recognize \"provisional\" or
\"interim\" approval of any animal study proposal.

*4. Does the PHS Policy place any proscriptions on filling the positions
of IO, attending veterinarian, and IACUC Chairperson with the same
individual?*

While there are no specific prohibitions, OPRR strongly recommends
against having more than one of these positions filled by the same
individual. OPRR considers that the responsibilities and authorities
vested in each of the aforementioned positions are distinct, often
requiring different skills. Also, the assignment of more than one of
these roles to the same individual circumvents the intended checks and
balances designed by the framers of the PHS Policy. Circumstances
arising from having the same person serving as the IACUC Chair, the
institutional veterinarian, and the IO have, in the past, been an
underlying factor in some of our most serious cases of noncompliance
with the PHS Policy. In addition, the mere perception of conflict of
interest may lead to allegations of improprieties from various sources.
However, the intent of the PHS Policy is to provide levels of
responsibility and authority within institutions which would provide an
optimal environment for its implementation. Hence, the attending
veterinarian, as the only member appointed by virtue of position, serves
on the IACUC under the IACUC Chairperson, with the later reporting
directly to the IO. This arrangement, however, should not preclude the
veterinarian from performing the appropriate management and
administrative functions as the institutional veterinarian with direct
access to (and preferably reporting channels to) the IO.

*5. Under the conditions of the Animal Welfare Assurance, is it
necessary for our IACUC to report to OPRR any suspensions of
animal-related activities or other sanctions imposed by the IACUC if the
subject activities are not PHS supported?*

While a few institutional laboratory animal care and use programs can be
subdivided into physically and operationally distinct entities, program
oversight is almost always exercised *institution-wide* under a single
institutional standard for animal care and use. OPRR has found that
deviations from IACUC policies and procedures, whether sufficiently
serious to impose protocol suspensions or minor in nature, generally
include issues that have bearing on compliance with the PHS Policy.
Unless OPRR has approved an Institutional Assurance that exempts
specific facilities or programs, it is expected that protocol
suspensions or other sanctions imposed by the IACUC on non-PHS supported
work will be reported. This will allow an evaluation of the potential
impact of the infraction on studies that are conducted with PHS support.
An additional reason for such reporting is to provide OPRR with advanced
knowledge of an incident *prior* to having it appear in the form of an
official complaint or congressional inquiry. This knowledge allows OPRR
to respond positively to outside inquiries that the system of animal
welfare oversight is working as intended.

*6. Our institution\'s animal care and use program is constantly
undergoing modification, much of which we consider to be minor. In its
Annual Report to OPRR, how extensively must institutional facility and
program changes be described?*

The approved Animal Welfare Assurance is the key document in defining
the relationship between the institution and the PHS. Institutions
should therefore consider any program or facility modification that
results in a change to any item described in its Assurance to OPRR as
reportable. Facility modifications generally involve changes in gross
square footage resulting from the addition (either newly-constructed or
otherwise acquired) or elimination of animal space.

Normally, it is not necessary to report preventive maintenance items or
remodeling that does not result in changes to the gross square footage
or carrying capacity of the facility. Annual Reports should identify the
affected areas, the number of square feet involved, and resultant
changes in the average daily animal populations. Concerning program
matters, OPRR needs to be kept informed of any modifications in
institutional lines of authority and responsibility and of any changes
in key personnel such as the institutional official, the IACUC
chairperson, and the veterinarian. Another consequential programmatic
consideration includes changes in the composition and procedures of the
IACUC that represent departures from those described in the Assurance.
Similarly, any significant changes made in the occupational health and
training or instruction programs should be brought to the attention of
OPRR in the annual report. Finally, the Report should include
significant changes in the numbers and species of animals maintained by
the institution. These elements are especially important in OPRR\'s
evaluation of the adequacy of veterinary resources, credentials, and
support facilities.

The extent to which program or facility modifications or changes need to
be described in an annual report will depend on the degree to which they
differ from the corresponding items described in the Assurance. OPRR
recommends that the descriptions be comprehensive and in sufficient
detail to allow replacement of the affected items as they were described
in the original Assurance.

*7. Implementing regulations of the Animal Welfare Act require that
animal study protocols be reviewed and acted upon by the IACUC annually.
The PHS Policy requires that such reviews be conducted every three
years. For the purpose of complying with OPRR\'s oversight policy, how
frequently must our IACUC perform such reviews?*

The PHS Policy requires that *de novo* IACUC reviews of all
PHS-supported protocols be conducted on a triennial basis. The Policy
also states that \"\... institutions are required to comply \... with
the Animal Welfare Act, and other Federal statutes and regulations.\" To
be compliant with the USDA\'s Animal Welfare Regulations, the IACUC must
review those protocols involving dogs, cats, nonhuman primates, rabbits,
guinea pigs, and hamsters each year to assure active status and to
identify significant changes. Although annual reviews of protocols
involving other species are not required under the PHS Policy, many
institutions will choose to establish a uniform method covering all
vertebrate species that satisfies the USDA\'s requirement for annual
review and the PHS requirement to review and approve proposals for
significant changes to ongoing protocols. A relatively simple monitoring
mechanism, which meets USDA requirements and serves to monitor animal
activities covered by the PHS Policy, can be implemented by the use of a
standard form containing basic protocol information (including title,
approval number, date, and species). This form is then sent to the PI to
(1) verify active status, (2) verify that completed activities were
conducted in accordance with the approved protocol, (3) describe any
proposed departures from the approved protocols, and (4) solicit
information about activities projected for the upcoming year.
Information pertaining to the future would indicate either that no
changes were proposed or describe changes that the PI would like to
implement. Any proposed changes deemed to be significant would then be
brought before the IACUC for its consideration and documented as an
official IACUC action. Such a monitoring system, however, does not
preclude the requirement for triennial review or for PIs to seek IACUC
approval when they want to make significant changes in approved
protocols at other than the regularly scheduled monitoring periods. Such
approval must be obtained *prior* to implementing the changes. Both the
USDA and PHS requirements, of course, may also be satisfied by
conducting complete *de novo* reviews of all animal study proposals on
an annual basis.

REFERENCES

NRC (National Research Council). 1985. Guide for the Care and Use of
Laboratory Animals. A report of the Institute of Laboratory Animal
Resources Committee on Care and Use of Laboratory Animals. Washington,
D.C.,: U.S. Department of Health and Human Services.

Public Health Service (PHS). 1986. Public Health Service Policy on
Humane Care and Use of Laboratory Animals. Washington, D.C.: U.S.
Department of Health and Human Services. (Available from: Office for
Protection from Research Risks, Building 31, Room 4B09, National
Institutes of Health, Bethesda, MD 20892).

Health Research Extension Act of 1985. P.L. 99-158.

Animal Welfare Act of 1966 (P.L. 89-544) inclusive of amendments; 1970
(P.L. 91-579; 1976 (P.L. 94-279); 1985 (P.L. 99-198).

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**ILAR News. 1991**; 33(4):68‑70. The PHS Responds to Commonly Asked
Questions.

\[This report was prepared by the staff of the Division of Animal
Welfare, Office for Protection from Research Risks, National Institute
of Health, in Bethesda, Maryland.\]

The National Institutes of Health\'s (NIH\'s) Office for Protection from
Research Risks (OPRR) is responsible for developing, implementing, and
overseeing compliance with the Public Health Service (PHS) Policy on the
Humane Care and Use of Laboratory Animals (Policy). The PHS Policy,
along with the U.S Department of Agriculture\'s (USDA\'s) Animal Welfare
Regulations, are the two principal federal documents setting forth
requirements for animal care and use by institutions using animals in
research, testing, and education. A primary function of OPRR in
assisting institutions in implementing PHS Policy is to respond to
policy-related questions.

The following represent a few of the most commonly asked questions from
institutions and the OPRR responses:

*1. Are avian embryos covered by the PHS Policy, i.e., must their
proposed use be reviewed and approved by institutional animal care and
use committees (IACUCs)?*

PHS Policy is applicable to proposed activities that involve live
vertebrate animals. While embryonal stages of avian species develop
vertebrae at a stage in their development prior to hatching, OPRR has
interpreted \"live vertebrate animal\" to apply to avians (e.g., chick
embryos) only after hatching.

*2. May our institution apply the requirements of the PHS Policy
exclusively to activities that are supported by the PHS? In other words,
may we apply different requirements for application and proposal review
when the proposed work is funded by another agency or is it to be
conducted with internal institutional funds?*

Institutional adherence to PHS Policy is a requirement for all
activities supported by the PHS, most commonly through NIH grants or
contracts, but also including other forms of PHS support such as
collaborations and postdoctoral stipends. Since the 1985/1986 revisions
to the PHS Policy, the vast majority of institutions filing Animal
Welfare Assurances with OPRR have chosen to apply the Policy
requirements to all activities involving animals at their institution.

Until 1989, dual mechanisms with PHS-supported and non PHS-supported
activities were theoretically possible. With the finalization in 1989 of
Part 2 of the USDA regulations, which includes administrative
requirements for proposal review, veterinary care, and personnel
qualifications, such dual systems are impractical. Part 2 of the USDA
regulations are virtually identical to the PHS Policy. Thus,
institutions using species covered by the USDA regulations (which
currently exclude mice and rats) must establish programs and follow
procedures identical to those required by the PHS Policy in order to
meet USDA requirements. A more pragmatic reason for having a uniform
institutional policy has to do with the public relations dilemma of
trying to defend a double standard of humane care for animals.
Accordingly, institutional policies should be designed with an emphasis
on the desired outcome of appropriate humane care and use of all animals
at the institution.

*3. Our institution requires that when the IACUC meets, not only must a
majority of the members be present, but that the quorum must include the
institutional veterinarian and a nonaffiliated member. Is this
requirement in keeping with PHS Policy?*

Two issues are actually contained in this question: (1) Must the
veterinarian and/or nonaffiliated member be present for all formally
convened meetings of the IACUC? and (2) May an institution impose
requirements more stringent than the corresponding provision of the PHS
Policy? The PHS Policy is silent on the first question. OPRR has
interpreted the Policy to provide that, with respect to the IACUC, all
members are equal. Thus there is no requirement that the veterinarian
and/or the nonaffiliated member be present for every IACUC meeting.
Attention should be paid by institutions to attendance at IACUC meetings
ensuring that an appropriate mix of members attends all meetings and
that frequent absences from such meetings by any member are avoided. No
member may be excluded from any IACUC function (e.g., semiannual
reviews). A history of nonattendance by IACUC members, especially those
required by statute, will always arouse the suspicion of a site visitor
or inspector.

With regard to the second question, institutionally imposed requirements
that exceed those of the PHS Policy are not proscribed by the Policy.
Additional requirements may be imposed by the institution at its
discretion, bearing in mind that the spirit of the PHS Policy is to
promote humane care and use of animals, while facilitating the pursuit
of legitimate scientific objectives.

*4. Is it permissible under PHS Policy to reimburse the nonaffiliated
member of the IACUC?*

Meeting fully the letter and spirit of the PHS Policy (and USDA
regulations) requires that the nonaffiliated IACUC member be completely
disinterested in the institution\'s profit or benefit from proposed
activities that involve animals. While in the vast majority of instances
effective nonaffiliated IACUC members may be willing to serve without
reimbursement, in other instances remuneration may allow for
participation by effective individuals that would not otherwise be
possible. Both OPRR and USDA maintain that nominal compensation is
permissible without jeopardizing a member\'s nonaffiliated status, if it
is only in conjunction with service on the IACUC. The level of
reimbursement varies from payment of travel and related expenses, such
as parking and meals, to modest monetary payments for participation in
this capacity. The dollar amount of compensation, if any, should not be
so substantial as to be considered an important source of income or to
influence voting on the IACUC.

*5. In fulfilling its requirements under PHS Policy and USDA
regulations, must the IACUC inspect every laboratory or other site where
investigators use animals?*

When considering IACUC responsibilities for semiannual review, it is
important to keep in mind that the institution, usually acting through
the IACUC and/or the facility veterinarian, is responsible for all
animal-related activities of the institution, regardless of where
animals are maintained or the duration of their stay. The PHS Policy
allows institutions some discretion regarding specific methods to assure
compliance, but the institution is clearly responsible for what happens
to animals in investigators\' laboratories. The degree, method, and
frequency of IACUC oversight depends a great deal on the nature of the
activity. For example, satellite holding facilities or areas where
surgical manipulation is conducted should always be included in the
semiannual review. Other activities, such as routine dosing, weighing,
or immunization of animals in laboratories, may be monitored using other
methods such as random evaluation.

Inclusion of these laboratories in the semiannual IACUC review would be
another way to satisfy the PHS Policy requirements. In any case, the
IACUC must have access to all investigators\' laboratories for the
purpose of verifying that activities involving animals are conducted in
accordance with the proposal approved by that committee.

*6. The PHS Policy requires semiannual IACUC inspection of all
facilities where animals are held for 24 hours or more, while the USDA
regulations require such inspections of sites where animals are kept for
12 hours or more. How should our IACUC deal with this discrepancy?*

The PHS Policy requires compliance with the Animal Welfare Act. The USDA
regulations apply to animal study areas where USDA-covered species are
maintained for more than 12 hours. These areas of the facility must be
included in the semiannual review. The PHS Policy definition of
satellite facility and duration of stay requirements remain unchanged,
and may be applied to species such as rats and mice that are covered by
the Policy but not by USDA regulations. The important point to remember
is that the institution remains accountable for all activities involving
animals, regardless of any technical differences in definitions and time
limits. Again, institutional policies should be designed with an
emphasis on the desired outcome of appropriate humane care and use of
all animals at the institution.

7\. *To what extent, if any, is the IACUC responsible for assessing the
scientific merit of proposals it reviews?*

Peer review of the scientific merit of a proposal is considered to be
the purview of the PHS funding component, acting through an initial
review group (IRG). The PHS Policy requires the funding component to
verify that the IACUC has reviewed and approved animal activities before
the PHS awarding unit makes an award. Additionally, the IRG has the
authority to raise specific animal concerns. The primary focus of the
IRG is scientific merit, whereas the primary focus of the IACUC is
animal welfare. It is evident, however, that there is some overlap of
function between the two bodies.

Although not intended to conduct peer review of research proposals, the
IACUC is expected to include consideration of the *U.S. Government
Principles for the Utilization and Care of Vertebrate Animals in
Testing, Research, and Training* (PHS Policy) in its proposal review
process. Principle II calls for an evaluation of the relevance of a
procedure to human or animal health, the advancement of knowledge, or
the good of society. Other references (sections IV.C. I and IV.D. 1.)
include language such as \"consistent with sound research design,\"
\"rationale for involving animals,\" and \"in the conduct of
scientifically valuable research,\" which presumes that the IACUC will
consider in its review the general scientific relevance of the proposal.
The presumption is that a study that could not meet these basic tests
would be inherently invalid or wasteful and, therefore, not justifiable.

*8. The PHS Policy requires that the IACUC \"conduct continuing review
of activities\" at least every 3 years, while the USDA regulations
require such review annually. How can our IACUC best meet both these
requirements?*

The frequency of IACUC consideration of approved, ongoing activities is
one of the few areas in which the PHS and USDA have differing
requirements, that is, PHS requires it at least once every 3 years,
whereas USDA requires it annually. While USDA\'s exclusion of rats,
mice, and birds allows for dual mechanisms of IACUC monitoring of
activities involving USDA- covered species annually and activities
involving all other species triennially, many institutions will choose
to establish uniform procedures that satisfy both of these federal
requirements.

It is helpful in considering this issue to refer to the evaluation of
ongoing activities by use of the term monitoring, as opposed to the
function that the IACUC performed at the outset of a new activity and at
the expiration of an approved activity, which may be called review. OPRR
has interpreted the PHS Policy to require an institutional process that
provides review of proposed activities, with committee approval for a
specified period of time not to exceed 3 years. This review and approval
may be accomplished by either convened committee action or by a
designated reviewer/expedited review process that meets the PHS Policy
requirements of Section IV.C.2.

During this period of approval, monitoring may be done on an annual
basis to meet USDA requirements. The purpose of monitoring is to ensure
that no changes have taken place inadvertently in the approved activity
that might require further review by the IACUC and that any new
requirements of the PHS, USDA, or the institution are transmitted to the
investigator. Monitoring need not require convened IACUC or designated
reviewer/expedited action. A relatively simple mechanism to meet both
federal requirements is to circulate annually to all investigators with
IACUC-approved activities a standard form giving current basic
information, such as IACUC approval number, IACUC approval date, title
of project, and species used. The investigator then notes that either no
changes have taken place, or he/she describes any changes that have
occurred. Responses are reviewed by an IACUC-designee for assessment of
the changes reported. Any changes to the approved activity that are
deemed of sufficient magnitude to merit further consideration may then
be presented to the IACUC. All of these dispositions should be
documented as official IACUC actions.

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