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) that require institutions to establish and maintain proper measures to ensure the appropriate care and use of all vertebrate animals involved in research, research training, and biological testing activities conducted or supported by the U.S. Federal Government.

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

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 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?

Reporting

Annual Report to OLAW changed to DEC 1st and covers fiscal year in harmony with USDA report

USDA has created an online portal for reports that will be update with user feedback

USDA removed the need to renew registration every 3 years but instead include relevant info in annual report

USDA eliminated requirement of CEO/IO signature on annual report

Domestic animal assurance can use parts of AALAC program description

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

PHS policy requires that the IACUC consist of at least five members, including: a veterinarian, a scientist with animal research experience, a member from a non-scientific area, and one not affiliated with the institution; appointed by CEO (AWA requires at least three members including the attending veterinarian and a member not affiliated with the institution)

What is the administrative hierarchy of OLAW? Which office is OLAW under?

The PHS Policy is administered by the Office Laboratory Animal Welfare (OLAW) under the Office of Extramural Research by the Office of the Director of the National Institutes of Health (NIH) of the US Dept of Health and Human Service.

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- 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-What is the definition of satellite facility? housing animal for more than ____hrs?

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

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-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; consistent with the 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-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?

The 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

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

Category One Institute's are

-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 Institute's are

-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

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 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 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- 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

PHS and AWA: How often does de novo review for protocol occurs?

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

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 shall take corrective action and report to OLAW

PHS-What is Vertebrate Animal Section?

VAS includes

Description of procedures

Justifications for species and why no alternatives

Description of pain interventions

Consistent/not with AVMA guidelines

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

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

If directly related to an animal activity then it must be kept for the duration of the activity and then for an additional 3 years

-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;13 or

c. any suspension of an activity by the IACUC.

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.

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 (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.

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.

PHS (FAQs)-Are institutions required by FOIA to release information about their research, animal care programs, and IACUCs?

No, but... State or local laws, sometimes referred to as "Sunshine Laws" may govern the release of information by institutions.

Federal institutions are subject to FOIA

PHS (FAQs)-What are PHS requirements for recording and reporting minority views? What is the difference between minority view versus dissenting vote?

-Maintain records of minority views expressed (1) as recommendations to the IO and/or (2) during semiannual inspections. Included in the Annual Report to OLAW.

minority view vs. dissenting vote.

• A dissenting vote on protocol/amendments must be recorded in the minutes, this does not constitute a minority view.

•A minority view to OLAW is addressing any aspect of the institution's animal program, facilities, or personnel training.

PHS (FAQs)-How frequently should the IACUC review research protocols?

Under PHS Policy the maximum interval between IACUC review and approval is three years - a complete de novo review is required at least every three years.

PHS (FAQs)-May the IACUC administratively extend approval of a project that has expired?

No. Continuation of animal activities in the absence of valid approval is a serious and reportable violation of PHS Policy.

PHS (FAQs)-What are the possible methods of IACUC approval?

Two valid methods of IACUC review: (1) full-committee review or (2) designated member review.

PHS (FAQs)-What are the possible outcome of full committee review?

approval, a requirement for modifications (to secure approval), or withholding of approval

PHS (FAQs)-What are the possible outcome of designated member review?

approval, a requirement for modifications, or referral to the full committee (not withholding approval).

PHS (FAQs)-May the IACUC grant conditional or provisional approval?

No, applying descriptors, such as conditional, provisional or interim, when referring to IACUC approval is unclear, confusing, and should be avoided.

PHS (FAQs)-May the investigator begin animal work before receiving IACUC approval?

No

PHS (FAQs)-What criteria should the IACUC consider when reviewing protocols?

IACUCs must confirm that the protocol:

1) is consistent with the Guide unless a scientific justification for a departure is presented and is acceptable to the IACUC;

2) conforms with the institution's Assurance;

3) will be conducted in accordance with the USDA Animal Welfare Regulations if applicable.

4)meets the requirements of the PHS Policy.

PHS (FAQs)-What are the 9 things in U.S. Government Principles?

1.AWA

2.Relevance to human and animal health

3.Appropriate species and number

4.Minimization of distress and pain

5.Appropriate sedation, analgesia or anesthesia

6.Euthanasia

7.Living conditions

8.Training

9.Exceptions

PHS (FAQs)-When institutions collaborate, or when the performance site is not the awardee institution, which IACUC is responsible for review of the research activity?

-Institutions should have a formal written understanding (e.g., memorandum of understanding) that addresses responsibilities for animal care and use, ownership, and IACUC review and oversight.

-PHS Policy requires that awardees and performance sites hold an approved Assurance. If both the awardee institution and the performance site have Domestic Assurances, they may exercise discretion in determining which IACUC reviews activities and under which program the research will be performed.

PHS (FAQs)-May the IACUC approve pilot studies?

Yes

PHS (FAQs)-Is the IACUC required to review the grant application?

No. However, institutions are responsible for ensuring that the information the IACUC reviews and approves is congruent with what is in the application/proposal.

PHS (FAQs)-Is the IACUC responsible for judging the scientific merit of proposals?

No. The primary focus of the IACUC is animal welfare.

PHS (FAQs)-Is IACUC approval required for the collection of samples in foreign countries from captive wild animals or research colonies?

Yes. Collection of biological samples from any live vertebrate animal for the purpose of a PHS-supported activity is covered by the PHS Policy.

PHS (FAQs)-If an animal activity will be performed outside of the US (either by a foreign awardee or by a foreign institution as a subproject for a domestic awardee), is the awardee's IACUC required to review and approve that activity?

When the awardee is a domestic institution (i.e., domestic award with a foreign component), PHS animal welfare requirements are applicable. Accordingly, the awardee remains responsible for animal activity conducted at a foreign site and must provide verification of IACUC approval. If the prime awardee is a foreign institution, IACUC approval is not required.

PHS (FAQs)-May standard operating procedures (SOPs) or blanket protocols that cover a number of procedures be utilized in lieu of repeating descriptions of identical procedures in multiple protocols?

IACUCs may approve SOPs that can be cited by investigators in their protocols in order to avoid needless repetition. SOPs should be reviewed by the IACUC at appropriate intervals (at least once every three years).

PHS (FAQs)-Is IACUC approval required for the use of animals in breeding programs, as blood donors, as sentinels in disease surveillance programs, or for other non-research purposes?

Yes

PHS (FAQs)-What guidelines should IACUCs follow for fishes, amphibians, reptiles, birds, and other nontraditional species used in research?

PHS Policy is intentionally broad in scope allowing for professional judgment. The Guide can generally be adapted to the care and use of various kinds of nontraditional research animals. Appendix A of the Guide references many such publications.

PHS (FAQs)-Is it acceptable to have different individuals named as PI on the grant application and the IACUC protocol?

Yes

PHS (FAQs)-Can a quorum of the IACUC decide to establish the DMR subsequent to FCR policy?

No. Only by unanimous consent of all members of the IACUC.

PHS (FAQs)-What does "in advance, in writing" mean?

The IACUC-approved policy must be in place prior to the first meeting at which it is used.

PHS (FAQs)-When can the IACUC start using DMR subsequent to FCR?

As soon as all members agree to the process and the IACUC-approved, written DMR subsequent to FCR policy and procedures are in place.

PHS (FAQs)-May an IACUC use designated member review (DMR) to review an animal study protocol subsequent to full committee review (FCR) when modifications are needed to secure approval?

1) If all members of the IACUC are present at a meeting, the committee may vote to require modifications to secure approval and have the revised research protocol reviewed and approved by designated member review, or returned for FCR at a convened meeting.

2) If all members of the IACUC are not present at a meeting, the committee may use DMR subsequent to FCR if a)All IACUC members agree in advance in writing that the quorum of members present at a convened meeting may decide by unanimous vote to use DMR subsequent to FCR.

b)Institutions should specify its intention to conduct reviews in this manner in its Assurance with OLAW.

3)If all members are not present and the IACUC lacks written standard procedures as described above, the committee has the option to vote to return the protocol for FCR at a convened meeting or to employ DMR. All members, including the members not present at the meeting, must have the revised research protocol available to them and must have the opportunity to call for FCR.

PHS (FAQs)-Should the IACUC inspect laboratories or other sites where investigators use animals?

Institutions are responsible for oversight of all animal-related activities; this includes housing area, satellite facilities, surgical manipulation area

PHS (FAQs)-What is the definition of animal study areas by USDA?

USDA requires semi-annual inspection of "animal study areas" defined as areas where USDA covered animals are housed for more than 12 hours.

PHS (FAQs)-How does the IACUC distinguish between significant and minor deficiencies?

1) A significant deficiency is defined as one which is or may be a threat to the health or safety of animals. Significant deficiencies require a timeline for remedy

2) minor deficiency refers to a problem for which an immediate solution is not necessary to protect life or prevent distress

PHS (FAQs)-May the IACUC use an AAALAC International site visit as its semiannual evaluation?

Yes, if you meet req. of AAALAC site visit and 2 IACUC members are present for site visit

PHS (FAQs)-Is the IACUC required to inspect field study sites?

Not required. IACUCs should be apprised of the circumstances under which studies are conducted

PHS (FAQs)-Is the use of carbon dioxide an acceptable euthanasia agent?

Yes, must follow AVMA Guidelines for the Euthanasia of Animals.

A gradual displacement rate of 30% to 70% to minimize aversion and distress. It is important to verify death after CO2 exposure.

PHS (FAQs)-Is the IACUC responsible for tracking animal usage?

This implicitly requires that institutions establish mechanisms to document and monitor numbers of animals acquired and used, including any animals that are euthanatized because they are not needed

PHS (FAQs)-May an investigator transfer animals and research to an institution different than the grantee institution?

Requires the prior approval of the funding component. The proposed new grantee institution must have or obtain an Animal Welfare Assurance

PHS (FAQs)-May investigators use non-pharmaceutical-grade substances in animals?

OLAW and USDA agree that pharmaceutical-grade substances, when available, must be used.

PHS (FAQs)-May investigators use expired pharmaceuticals, biologics, and supplies in animals?

Not consistent with acceptable veterinary practice or adequate veterinary care. Euthanasia, anesthesia and analgesia agents should not be used beyond their expiration date, even if a procedure is terminal. Other expired materials should not be used unless the manufacturer verifies efficacy beyond the expiration date, or the investigator is able to document to the satisfaction of the IACUC