02. PHS policy

Which entity administer/ enforce/ over see The Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy)?

Office of Laboratory Animal Welfare (OLAW)

What are the two principle federal laws that govern animal welfare in the US?

1. Animal Welfare Act (United States Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) or the USDA)

2. Health Research Extension Act of 1985 (Office Laboratory Animal Welfare (OLAW) of the National Institutes of Health (NIH))

What is the public law that provides statutory mandate for PHS policy?

Health Research Extension Act of 1985

What is the purpose of 21ST Century Cures Act?

is designed to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently. reduce administrative burden

In 21ST Century Cures Act, there are 3 paragraphs that are pertinent to veterinarians; what are the three main things

1. Reducing administrative Burden for researchers

2. Enhancing the rigor and reproducibility of scientific research

3. Clarifying Food and Drug Administration emergency use authorization

Based on 21ST Century Cures Act, how often should protocol occur based in the updated AWR?

Protocol Review - AWR changed requirement for annual review to complete review every 3 years in harmony with PHS Policy.

Based on 21ST Century Cures Act, how often should reporting occur? What other changes were made to alleviate administrative burden?

1) Annual Report to OLAW changed to DEC 1st (same as USDA)

2) USDA - online portal for reports

3) USDA - instead of renew q3yr, include relavent info on annual report

4) USDA - no longer need CEO/IO signature on annual report

5) Domestic animal assurance - can use parts of AALAC program description

Who administers the PHS policy (who is it under)?

OLAW (Office of laboratory animal welfare)

What is the administrative hierarchy of PHS policy and OLAW? Which office is OLAW under?

PHS policy →

Office of Extramural Research →

Secretary acting through Director of the National Institutes of Health (NIH) →

US Dept of Health and Human Service

The IACUC should follow PHS policy if an institution receives funds from what two institutions?

NIH (National Institute of Health)

NRI (National Research Institute)

Where does PHS policy apply?

All PHS conducted or supported activites involving animals in

US, Peurto Rico, any territory or possession of US (Awardee institution, PHS agency, any other institutions)

What if the awardee of NIH money is in a foreign country? Do they need to comply with PHS policy? Whose laws apply?

Institution must comply with PHS policy or provide evidence of other similar standards being met

if more stringent laws/regs locally - follow those

NO PHS support will be provided to individuals unless affiliated with or sponsored by ____

an institution that assumes responsibility for compliance with the Policy

In addition to the PHS policy, awardees must also comply with what other regulation?

AWA

According to PHS Policy, who appoints the IACUC committee?

Chief Executive Officer of Entity

PHS- Who appoint the IACUC members? How many member and what role?

PHS IACUC - 5 members - appointed by CEO

a veterinarian

a scientist

a non - scientist

a not affiliate

(AWA - 3 members - Chair & AV & non affiliate)

PHS- What is considered an animal?

Any live vertebrate animal used or intended for

use in research

research training

experimentation

biological testing

or for related purposes

doesn't cover embryos until hatched

cover zebrafish right after hatch

doesn't cover the dead (AWA does)

PHS - Definition of an animal facility?

 any and all buildings, rooms, areas, enclosure, or vehicles, including satellite facilities, used for animal confinement, transport, maintenance, breeding, or experiments inclusive or surgical manipulations

PHS-What is the definition of satellite facility? housing animal for more than ____hrs? How does this differ from the AWA?

is any containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 24 hours.

AWA is if animals are housed for more than 12 hours

Who administers the AWA?

USDA

PHS- What is animal welfare assurance? Where do the insurance get sent to?

Documentation from an institution assuring institutional compliance with PHS Policy.

OLAW

PHS - what is an institution?

Any public or private organization, business, or agency (including parts of Federal, State, and Local governments)

PHS - Who is the institutional official?

individual who signs and has the authority to sign the institution’s assurance, making a commitment on behalf of the institution that the requirements of the policy are met

What are PHS agencies?

Agency for Health Care Research and Quality;

Agency for Toxic Substances and Disease Registry;

Biomedical Advanced Research and Development Authority;

Centers for Disease Control and Prevention;

Food and Drug Administration;

Health Resources and Services Administration;

Indian Health Service;

National Institutes of Health; and

Substance Abuse and Mental Health Services Administration.

PHS - define a Quorum

majority of IACUC members are present

PHS-In the assurance, what is it based on (PHS mandates institutions to use _____ as base)? What regulations does the assurance have to comply to?

Guide

USDA under animal welfare act

Euthanasia consistent with AVMA Guidelines

U.S. Government Principles

Who signs the written assurance to OLAW, NIH?

Institutions must submit a written assurance to OLAW, NIH signed by the IO that it will comply with the PHS Policy

PHS - once the assurance is submitted, OLAW will do one of three things

approve, disapprove, or negotiate and approvable version of the Assurance

PHS-How long is assurances approved for?

Assurances are approved for a specified period of time, no longer than 5 years (Domestic assurances 4 years per FAQs)

PHS- What are the 3 types of assurances?

-Domestic Assurances are negotiated with U.S. institutions that control their own animal facilities, conduct animal research on-site, and have an animal care and use program with an Institutional Official, an IACUC, and a veterinarian with program authority.

-An Interinstitutional Assurance is required if the grantee organization has no animal facility and will do the work at an Assured performance site. The Interinstitutional Assurance binds the awardee institution with the Assured performance site to ensure the humane care and use of animals.

-A Foreign Assurance is required if the direct award is made to an institution outside the U.S, or if the domestic awardee has a foreign performance site. In the situation where there is collaboration between a domestic awardee and a foreign institution, the domestic institution must provide IACUC approval.

PHS-What is the annual report to OLAW and when is it due?

-Annual Report is a document prepared by the IACUC and submitted to OLAW through the Institutional Official.

-It describes any changes in the institution's program of animal care and use, AAALAC International accreditation status, changes of Institutional Official and in IACUC membership, the dates that the IACUC conducted its semiannual evaluations of the program and facilities, and any minority views.

-Due on December 1st

PHS-When is the annual report to OLAW due?

Beginning in 2021, the reporting period for the Annual Report to OLAW is the Federal fiscal year, October 1 to September 30, with the Annual Report due on or before December 1 (but no earlier than September 30).

PHS assurance Program of Animal Care & Use Components cover?

1. IACUC

2. IACUC procedures (SOPs)

3. Vet Care

4. Personnel Qualifications & Training

5. Occupational Health & Safety

6. Animal Facilities & Husbandry

7. Disaster & Emergency Preparedness

• List of every branch and major component of institution and any other institution included under Assurance. 

• Lines of authority and responsibility for administering the program and ensuring compliance with Policy. 

• Qualifications, authority, and responsibility of vets and % time contributed to program.

• IACUC committee members list. 

• Procedures IACUC will follow to fulfill requirements of Policy.

• Health program for personnel who work in lab or frequently contact animals. 

• Synopsis of training or instruction in humane practice of animal care and use, research or testing methods that minimize # of animals and distress – should be offered to scientists, animal techs, others involved in care, tx, or use. 

• Gross square footage of each facility (incl satellites), species housed, average daily inventory of animals (by species).

• Any other info requested by OLAW.

PHS-There are two categories of institution status. What does each entail?

Category One

-Evaluated and accredited by AAALAC

-Evaluated by the IACUC once every 6 month

-semi annual IACUC inspection doesn't need to be submitted to OLAW

Category Two

-NOT AAALAC accredited

-Evaluated by the IACUC once every 6 month

-Required to submit their most recent IACUC Semiannual Inspection report with Assurance

PHS- How many IACUC members are required and their roles?

At least five members

-at least one Vet with training or experience in laboratory ---animal science, who has direct or delegated responsibility for animals

-one practicing scientist w/ animal research experience

-one nonscientific member

-one individual who is not affiliated with the institution

Individuals may fulfill more than one requirement, but must have at least 5 members

PHS- Who appoints IACUC members? Who is considered the highest operating official of the organization?

CEO

PHS- What are the 8 functions of IACUC? (same as AWA)

1. Review the institution's program every 6 months using the Guide as the basis for evaluation

2. Inspect the facility every 6 months using Guide

3. Prepare reports to the IO; significant vs minor deficiencies, departures from Guide & Policy

-Significant deficiency: in the judgement of the IACUC AND the IO is or may be a threat to health and safety of animals

-Plan and schedule to correct each deficiency

-Reasons for departures

4. Review concerns involving care and use

5. Make recommendations to the IO animal program, facilities, personnel training

6. Review proposed activities

7. Review proposed significant changes

-Approve

-Require modification to secure approval

-Withhold approval

8. Be authorized to suspend activities

PHS - What 7 things must comply with the assurance to approve a protocol or amendment?

• Procedures avoid or minimize discomfort, distress, and pain (sound research design).

• Appropriate sedation, analgesia, or anesthesia provided if procedures cause more than momentary or slight pain or distress (unless justified).

• Animals that would otherwise experience unrelieved severe/chronic pain or distress will be painlessly euthanized at end of procedure or during. 

• Living conditions are appropriate for each species and contribute to health and comfort.  Vet or other trained scientist will direct housing, feeding, and nonmedical care. 

• Qualified vet will be available and provide medical care.

• Personnel will be qualified and trained to perform procedures.

• Euthanasia will be consistent with AVMA euthanasia guidelines (unless justified).

PHS- What is the fulfilment of full committee review? Who must be present to vote?

Must have:

Convened meeting of quorum

Approval vote of majority of the quorum

PHS- What is the definition of quorum? Quorum is required when _____ or _____an activity

A quorum is a majority of the total number of voting members of the IACUC.

-A quorum must be convened, and there must be a vote of the members present, in order for the IACUC to (1) conduct full committee review and approval of a proposed project or of a significant change to a project, and (2) suspend an activity.

Abstentions (abstaining voter) don't affect quorum number and do not change the number of votes required for approval

Conflict of interest may not contribute to the quorum for the vote on that project

PHS-Who designate designated member review of a protocol?

IACUC chair

PHS - Prior to each review, each IACUC member should get what?

-list of proposed protocols and written descriptions available

PHS - who can request a full committee review (FCR)?

Any committee member

PHS- DMR (may/may not) result in withholding of approval. FCR (may/may not) result in withholding of approval.**

DMR may NOT result in withholding of approval

FCR may result in withholding of approval

If FCR is not requested what must happen for the protocol or amendment to be approved?

one member (designated by chairperson and qualified) should approve, require modifications or request FCR

If FCR is requested what must happen for the protocol or amendment to be approved?

approval is granted after review at quorum meeting and approval of majority of quorum is present. No reviewing or contributing to quorum by members with conflicts excused in interest except to provide information

In an IACUC review, the IACUC can invite consultants to assist with reviewing complex issues, but consultants may NOT do what?

approve or withold approval or vote unless they are members of the IACUC

Once a protocol or amendment is approved, the IACUC shall notify investigators and institution ____ of decision. If the IACUC is withholding approval this correspondence should include what?

-in writing

-reason for withholding approval and allow response from investigator

PHS and AWA: How often does de novo review for protocol occurs? What else should happen?

at least once every 3 years; same as the Triennial review of protocol

review ongoing activities at appropriate intervals (post approval monitoring)

PHS-What does it take to suspend a protocol? Who is responsible to take corrective action and report to OLAW?

-an activity requires a convened meeting of a quorum of the IACUC with majority vote to suspend

-IO & IACUC shall take corrective action and report to OLAW

PHS - Protocols may be subject to additional approval ____ but that does not replace IACUC approval. This means that…

by officials of institution

officials may not approve activities that the IACUC has not approved

PHS-What is Vertebrate Animal Section? What must be included for non competing applications/contract proposals?

VAS includes

Description of procedures

Justifications for species and why no alternatives

Description of pain interventions

Euthanasia consistent/not with AVMA guidelines

Must have Assurance and signed verification of IACUC approval to receive $

non competing applications/contract proporsals - need not repeat information IF completed in last application - must state significant changes and reasons for them if application.

Prior to $ disbursement - For institutions that have approved assurance - applications and proposals should include verification of approval by IACUC including what?

date of approval

Prior to $ disbursement - For institutions that have approved assurance and this is a competing application - when can IACUC verification be filed? What if verification of IACUC approval is submitted after the application for $?

-any time prior to award unless required earlier by funding component

-verification must state any changes required by IACUC

-verifications must be signed bu individual authorized by institution (does NOT have to be IO)

Prior to $ disbursement - For institutions that do not have approved assurance - what must happen?

-signature of official signing for applicant organization should constitute a decleration that institution will submit an assurance when requested by OLAW

-upon OLAW request, assurance must be submitted after IACUC review

What is the take home message about $ disbursement in regards to institution?

You can apply for PHS funds before you have assurance by can’t actually get the money until you have assurance

PHS- Who is responsible for Congruence? (ensure that grant animal activity and animal use activity in the protocol agree)

institutional responsibility

PHS- Which studies require a VAS? Vertebrate Animal Section

You must provide a VAS if your work involves the use of live vertebrate animals, including generating custom antibodies and obtaining tissue from live vertebrate animals.

PHS- How many years should all animal related records be kept?

Institution shall maintain ALL records for a minimum of at least 3 years OR duration of activity and 3 years thereafter

-Proposals

-Significant changes

PHS- What is the IACUC reporting requirement? how often should the report to OLAW occur?

The IACUC, through the IO, must report every 12 months to OLAW

PHS- What is reportable in the annual report to OLAW?

-Changes that would alter Category 1 or 2 Assurance

-Any changes in the institution's facilities or program

-Changes in IACUC membership

-Any deviation/noncompliance/suspension and actions taken

-The dates of the semiannual program evaluation and reports to IO

-If no changes to report, tell them

-Include minority views

PHS-Must maintain records of Minority views recorded in which 2 situations?

1. Recommendations to the IO

2. Semiannual inspections

Minority veiws may be of the program, facilities, or personnel training.

PHS- 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

c. any suspension of an activity by the IACUC.

The PHS awarding Unit may NOT give an award unless the institution has ______.

-approved assurance on file with OLAW

-AND verification of protocol approval by IACUC is submitted

-If institution does not have approved assurance - awarding unit will ask OLAW to negotiate an assurance BEFORE award can be made

PHS - Awardee institutions are subject to review when?

ANY TIME by PHS staff and advisors, including site visits

PHS - Institutions may request a waiver of a provision or provisions of the Policy by submitting _____  - No waiver will be granted unless ____ is provided and the waiver is approved _____.

request to OLAW

sufficient justification and waiver approved in writing by OLAW

PHS/Guide- What deviations should be reported in the categories of MUST, SHOULD or MAY?

MUSTs are Minimum Standards

-Deviations w/ IACUC approval = departures 🡪 Semiannual report

-Deviations w/OUT IACUC approval = noncompliance 🡪 report PROMPTLY to OLAW through IO

SHOULDs are somewhere in between

-Well-established performance standards NOT departures

-Deviations w/ IACUC approval = departures 🡪 Semiannual report

-Deviations w/OUT IACUC approval = noncompliance 🡪 report PROMPTLY to OLAW through IO

MAYs are Suggestions

-Deviations 🡪 NOT included in semiannual report

PHS (FAQs)- Should institutions apply the PHS Policy to all animal activities regardless of the source of funding?

Impractical to separate based on funding but you could as long as it's in your assurance

The Assurance should explicitly reflect the exclusion of any specific area or activity.

Significant changes to AUP must be approved by ______.

valid IACUC approval method.

What are significant changes to an AUP that require IACUC approval?

• From nonsurvival to survival surgery

• Resulting in greater pain, distress, or degree of invasiveness

• In housing and or use of animals in a location that is not part of the animal program overseen by the IACUC

• In species 

• In study objectives

• In PI

• That impact personnel safety

Significant changes that may be handled administratively in consultation with a vet (VVC) with documentation (still subject to IACUC review if requested by Vet for any reason) include:

• Anesthesia, analgesia, sedation, or experimental substances

• Euthanasia to any method approved in AVMA guidelines 

• Duration, frequency, type, or number of procedures performed on an animals

Significant changes that may be handled administratively without a vet include:

• Increase in previously approved animal numbers 

• Correction of typos and grammar

• Contact information updates

• Change in personnel, other than PI

PHS (FAQs)- Does the PHS Policy apply to the production of custom antibodies or to the purchase of surgically modified animals?

Yes. It involves animals in research, so PHS policy applies and needs IACUC oversight and be covered in an assurance.

PHS - a nonaffiliated member must not be what 3 things?

• A laboratory animal user or former user

• Affiliated with the institution

• An immediate family member of an individual affiliated with the institution

PHS policy must be followed if funding is from what 3 major organizations?

-NIH

-CDC

-Other government funding (Health and Human services)

PHS (FAQs)- Does the PHS Policy apply to use of animal tissue or materials obtained from dead animals?

The use of dead animals or parts of animals is not covered by the PHS Policy unless the activity involves (1) killing animals or (2) project-specific antemortem manipulation of animals prior to killing them.

PHS (FAQs)-Does the PHS Policy apply to live embryonated eggs?

only after hatching.

PHS (FAQs)-Does the PHS Policy apply to larval forms of amphibians and fish?

Yes, larval forms of fish and amphibians have vertebrae and are covered by the PHS Policy. Zebrafish larvae, for example, typically hatch 3 days post-fertilization.

PHS (FAQs)- Does the PHS Policy apply to animal research that is conducted in the field?

If the IACUC determines that the proposed activity is likely to alter or influence the activity of the study animals or other species found in the study area, then protocol review and approval is required.

PHS (FAQs)- Does the IACUC need to approve research studies that use privately owned animals, such as pets?

Yes. The PHS Policy and the Animal Welfare Act and Regulations (AWAR) do not distinguish between animals owned by the institution and privately owned animals. Pets used in research must be covered under an IACUC-approved protocol.

PHS (FAQs)-How can the IACUC determine if activities involving privately owned animals constitute veterinary clinical care or research activities?

If the activity includes collection or generation of data for research purposes, it needs IACUC oversight.

If it's PHS funded, it needs an assurance.

PHS (FAQs)-What are the IACUC membership criteria?

5 members appointed by the CEO, filling 4 roles

Veterinarian

Scientist experienced in animal research

A non-scientist

Unaffiliated member

PHS (FAQs)-May the IACUC have alternate members?

Yes, must meet the qualification of the member they are replacing and can't be an alternate to multiple members

PHS (FAQs)-Must certain members be present in order to conduct official business?

No

PHS (FAQs)- Is a certain level of meeting attendance required of IACUC members?

No, Chronic non-attendance = looks bad

PHS (FAQs)- What is Recusal?

Members may not participate in the review or approval of a project in which they have a conflict of interest, except to provide information, and may not contribute to the quorum for the vote.

PHS (FAQs)-What information should be in IACUC minutes?

-records of attendance, activities of the Committee, and Committee deliberations.

-Documentation of major issues discussed by the IACUC and the outcome of the discussions in sufficient detail for an outsider to ascertain the nature of the discussion and the conclusions reached. Written transcripts or tape not req'd.

PHS (FAQs)-May an IACUC conduct business on a teleconference call?

Yes but must be given notice and meet all requirements of an in person meeting.

teleconference must allow real time verbal interaction and accurate count of any vote.

PHS (FAQs)-May an IACUC suspend (stop) animal activities that it did not initially approve?

Yes, and subsequently reported to OLAW because it constitutes serious noncompliance.

PHS (FAQs)-Does the Institutional Official have authority to halt an activity that was previously approved by the IACUC, or to approve one that was not initially approved by the IACUC?

The Institutional Official (or another authorized official) may unilaterally halt, terminate, or impose sanctions on any animal activity. The IO may not approve or reinstate any animal activity without IACUC approval.

IO can stop a project, but they can’t start it w/o IACUC approval

PHS (FAQs)-May the institution pay or reimburse expenses incurred by nonaffiliated members?

Yes. Nominal compensation for service on the IACUC, or reimbursement for expenses.The institution pay for IACUC training of nonaffiliated members.

PHS (FAQs)-How does OLAW define nonscientific IACUC member?

The nonscientific member is one who's primary concerns are in a nonscientific area (for example, ethicist, lawyer, member of the clergy). Want a diversity of perspectives and an individual with a naïve attitude with regard to science and scientific activities.

PHS (FAQs)-Does OLAW expect the IACUC to notify NIH when there is a change in an animal activity supported by PHS funds? What are the two types of changes? Who is responsible for requesting approval of a change in scope?

Change in scope = new protocol, Significant change = major amendment

-Change in scope refers to a change in the direction, type of research or training from the aims, objectives, or purposes of the approved project (ie Protocol). A change in an animal activity can be both a significant change requiring IACUC review and a change in scope (report to NIH). However, a significant change is not necessarily a change in scope.

Significant changes that require IACUC approval do not required to notify OLAW or the NIH funding component of this type of change.

The IACUC is not responsible for notifying the NIH of changes in scope; rather the Principal Investigator (PI) and the Authorized Organizational Official (AOO) are responsible for requesting approval of a change in scope.

PHS (FAQs)-How does OLAW define nonaffiliated IACUC member?

The nonaffiliated member is (1) not a laboratory animal user or former user, (2) not affiliated with the institution, or (3) not an immediate family member of an individual affiliated with the institution. Real or perceived conflicts of interest must be avoided.

PHS (FAQs)-May one individual fulfill the requirement for both a nonaffiliated and a nonscientific member?

Yes, as long as that individual meets the requirements for each position.

PHS (FAQs)-What is the annual report to OLAW?

Prepared by the IACUC and submitted to OLAW through the IO. It describes any changes in the institution's program of animal care and use, AAALAC accreditation status, changes of IO and in IACUC membership, dates of semiannual evaluations of the program and facilities, and any minority views.

PHS (FAQs)-When is the annual report to OLAW due?

The report covers the Fiscal Year (October 1 to September 30) with the report due to OLAW December 1 for the preceding fiscal year.

PHS (FAQs)-What kinds of situations should be reported to OLAW under IV.F.3. of the PHS Policy, and when, where, and how should they be reported?

Reported without delay:

Any noncompliance with this Policy

Any deviation from the Guide

Any suspension of an activity by the IACUC

If any question, call and ask.

PHS (FAQs)-Are all documents submitted to OLAW subject to the Freedom of Information Act?

Yes. All documents submitted to OLAW are subject to the FOIA.

PHS (FAQs)-Should the IACUC report sanctions other than suspensions that are imposed by the Committee or by other institutional officials?

Yes. Sanctions imposed by the IACUC or by an institutional official due to serious or continuing noncompliance or serious deviations from the Guide must be reported to OLAW.