PHS Policy on Humane Care and Use of Laboratory Animals
Frequently Asked Questions
Posted: September 11, 2006

References are to previously published guidance or commentary in Dear Colleague Letters, Lab Animal Magazine, Contemporary Topics, and ILAR News which may provide additional elaboration or commentary.  The information in this document is updated and supersedes previous guidance or commentary.

OLAW will update this page with new FAQs as necessary.

For questions about Assurances, email olawdoa@mail.nih.gov.
For questions about Compliance Oversight, email olawdco@mail.nih.gov
For general questions, email olaw@od.nih.gov

1.	Should institutions apply the PHS Policy to all animal activities regardless of the source of funding?
2.	Does the PHS Policy apply to the production of custom antibodies, or to the purchase of surgically modified animals?
3.	Does the PHS Policy apply to use of animal tissue or materials obtained from dead animals?
4.	Does the PHS Policy apply to live embryonated eggs?
5.	Does the PHS Policy apply to larval forms of amphibians and fish?
6.	Does the PHS Policy apply to animal research that is conducted in the field?

IACUC Composition, Functions and Authority

1.	What are the IACUC membership criteria?
2.	May the IACUC have alternate members?
3.	Must certain members be present in order to conduct official business?
4.	Is a certain level of meeting attendance required of IACUC members?
5.	What is a quorum and when is a quorum required?
6.	Does the IACUC have authority over activities not supported by PHS?
7.	What information should be in IACUC minutes?
8.	May an IACUC conduct business on a teleconference call?
9.	May an IACUC suspend (stop) animal activities that it did not initially approve?
10.	Does the Institutional Official have authority to suspend an activity that was previously approved by the IACUC, or to approve one that was not initially approved by the IACUC?
11.	May the institution pay or reimburse expenses incurred by nonaffiliated members?

1.	What is the annual report to OLAW and when is it due?
2.	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?
3.	Should the IACUC report sanctions other than suspensions that are imposed by the Committee or by other institutional officials?
4.	Are all documents submitted to OLAW subject to the Freedom of Information Act?

1.	How frequently should the IACUC review research protocols?
2.	May the IACUC administratively extend approval of a project that has expired?
3.	What are the possible methods of IACUC approval?
4.	May the IACUC grant conditional or provisional approval?
5.	May the investigator begin animal work before receiving IACUC approval?
6.	What criteria should the IACUC consider when reviewing protocols?
7.	Should the IACUC consider the three “Rs” of alternatives when reviewing protocols? (Refinements to research, Reduction of animal numbers, and Replacement with non-animal models)
8.	When institutions collaborate or when the performance site is not the grantee institution, which IACUC is responsible for review of the research activity?
9.	What is considered a significant change to a project that would require IACUC review?
10.	Is the IACUC required to review the grant application?
11.	May the IACUC approve pilot studies?
12.	Is the IACUC responsible for judging the scientific merit of proposals?
13.	If an animal activity will be performed outside of the US (either by a non-US grantee or by a foreign institution as a subproject for a domestic grantee), is the grantee’s IACUC required to review and approve that activity?
14.	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?
15.	Is IACUC approval required for the collection of samples in foreign countries from captive wild animals or research colonies?
16.	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?
17.	What guidelines should IACUCs follow for fishes, amphibians, reptiles, birds, and other nontraditional species used in research?

1.	Should the IACUC inspect laboratories or other sites where investigators use animals?
2.	How does the IACUC distinguish between significant and minor deficiencies?
3.	May the IACUC use an AAALAC inspection as its semiannual evaluation?
4.	Is the IACUC required to inspect field study sites?

Animal Use and Management

1.	Is the use of carbon dioxide an acceptable euthanasia agent?
2.	Is the IACUC responsible for tracking animal usage?
3.	May an investigator transfer animals and research to an institution different than the grantee institution?
4.	May investigators use non-pharmaceutical grade compounds in animals?
5.	May investigators use expired pharmaceuticals, biologics, and supplies in animals?
6.	How can institutions assure animal welfare when HVAC systems malfunction or fail?
7.	What are the requirements for conducting rodent survival surgery?
8.	Is the mouse ascites method an acceptable method of monoclonal antibody production?
9.	Are major multiple survival surgical procedures permitted on a single animal?
10.	May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density?

Institutional Responsibilities

1.	What kind of training is necessary to comply with the PHS Policy and how frequently should it be provided?
2.	What is required for an occupational health and safety program?
3.	Do grantee institutions need animal facility disaster plans?
4.	What kind of administrative organization works best for ensuring compliance?
5.	What is the difference between the Institutional Official and the Chief Executive Officer?
6.	Is post approval monitoring required?
7.	May institutions utilize the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (Ag Guide) if their program includes traditional farm animals?

Applicability of the PHS Policy

1. Should institutions apply the PHS Policy to all animal activities regardless of the source of funding?

   There are many valid reasons for institutions to perform program oversight institution-wide using uniform and consistent standards for animal care and use.  Likewise, it is generally impractical to separate activities based on the source of funding.  Institutions must implement the PHS Policy for all PHS supported activities involving animals, and must ensure that any standards that might not be consistent with PHS Policy do not affect or pose risks to PHS supported activities.  

   It is permissible for institutions to delineate animal areas that are programmatically and functionally separate and that do not support PHS animal activities such as a herd of beef cattle used for food production or a stable of riding horses.  The Assurance should explicitly reflect the exclusion of any specific area or activity.  [A1, A3, A4]
   

   
   

2.  Does the PHS Policy apply to the production of custom antibodies, or to the purchase of surgically modified animals?

   The generation of custom antibodies is considered an activity involving vertebrate animals and covered by PHS Policy.  Antibodies are considered customized if produced using antigen(s) provided by or at the request of the investigator (i.e., not purchased off-the-shelf).   An organization producing custom antibodies for a grantee must have or obtain an Assurance, or be included as a component of the grantee’s Assurance.  In addition, the applicant must provide the date (verification) of project-specific IACUC approval for the production of the antibodies. 

   The same guidance applies if surgery is conducted in response to a specific, custom request (as opposed to animals previously modified and available prior to the request).  An organization conducting custom surgery for a grantee must have or obtain an Assurance, or be included as a component of the grantee’s Assurance.  In addition, the grantee must provide the date (verification) of project-specific IACUC approval for conducting the surgery. 

   When both the grantee and subcontractor hold Assurances, some latitude is allowed in determining which IACUC will review the proposal.  However, the grantee always retains primary responsibility for ensuring compliance with PHS Policy.   [D6, A4, A11]
   

   
   

3.  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 for the purpose of obtaining or using their tissues or other materials, or (2) project-specific antemortem manipulation of animals prior to killing them.  If either circumstance is applicable to the acquisition of dead animals, body parts or tissues, prior IACUC protocol review and approval are required.
   

   

4. Does the PHS Policy apply to live embryonated eggs?
   

   Although avian and other egg-laying vertebrate species develop backbones prior to hatching, OLAW interprets the PHS Policy as applicable to their offspring only after hatching.  (The female egg-laying animal would be covered by the Policy.)  [A1] 

   
   

5. 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.

   

6. Does the PHS Policy apply to animal research that is conducted in the field?

   If the activities are PHS-supported and involve vertebrate animals then the IACUC is responsible for oversight in accord with PHS Policy.  IACUCs must know where field studies will be located, what procedures will be involved, and be sufficiently familiar with the nature of the habitat to assess the potential impact on the animal subjects.  Studies with the potential to impact the health or safety of personnel or the animal’s environment may need IACUC oversight, even if described as purely observational or behavioral.  When capture, handling, confinement, transportation, anesthesia, euthanasia, or invasive procedures are involved, the IACUC must ensure that proposed studies are in accord with the Guide.  The IACUC must also ensure compliance with the requirements of pertinent state, national and international wildlife regulations.

   A study on free-living wild USDA covered species that involves invasive procedures, harms or materially alters the behavior of an animal under study is covered by USDA animal welfare regulations and requires IACUC review and approval.

   See also question 4 under Program Review and Inspection of Facilities.

   
   

IACUC Composition, Functions and Authority

1. What are the IACUC membership criteria?

   The IACUC must consist of at least 5 members who are appointed by the institution's chief executive officer ( CEO ). If the CEO delegates appointment authority, the delegation must be specific and in writing.

   The appointed members must be qualified through experience and expertise to provide oversight for the institution's animal programs, facilities, and procedures. At a minimum the IACUC 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 (sometimes referred to as a public member). An individual who qualifies to fill more than one of the specified categories may be appointed to do so, but the committee must still consist of at least 5 members.

   The unaffiliated member should have no discernable ties or ongoing affiliation with the institution, and may not be a member of the immediate family of a person who is affiliated with the institution. Immediate family includes parent, spouse, child and sibling. Appointment of an individual who is unambiguously unaffiliated is the best way to fulfill the letter and spirit of this provision. PHS Policy incorporates the Guide which does not permit the nonaffiliated member to be a laboratory animal user. The veterinarian on the IACUC must have direct or delegated program responsibility for animal-related activities and therefore is always considered to be affiliated with the institution.

   If an appointed member who fulfills one of the required specified positions (i.e., scientist, nonscientist, veterinarian, or unaffiliated) leaves the committee so that that position is no longer filled, the IACUC is not properly constituted and may not conduct official business until a member who fulfills the required position is appointed by the CEO (or designee).

   OLAW strongly discourages filling the position of IACUC Chair, Institutional Official and veterinarian with the same individual due to the unique responsibilities and authorities of each position and the need for appropriate checks and balances. [A2, A7, A11, D5]
   

   

2. May the IACUC have alternate members?
   

   Provisions for appointing alternate members are addressed in the NIH Guide for Grants and Contracts NOT-OD-01-017.

   NOT-OD-01-017does not preclude designation of one alternate for multiple regular members, provided the alternate for a member fulfilling a specific membership requirement (e.g., nonscientist) also fulfills that requirement. An alternate may not represent more than one member at any one time. Conversely, it is permissible to appoint more than one alternate to represent a particular member, but again, if the member fulfills a specific membership requirement then the alternate must also fulfill that requirement.
   

   

3. Must certain members be present in order to conduct official business?

   The presence of any one specific member is not necessary in order to conduct official business or to meet the quorum requirement. [A1]
   

   

4. Is a certain level of meeting attendance required of IACUC members?

   Attention should be paid to attendance at IACUC meetings to ensure that an appropriate mix of members attends meetings. Chronic nonattendance by IACUC members, especially those explicitly required by PHS Policy or USDA regulations, implies a lack of participation in the oversight responsibilities of the IACUC. [A1]

   
   

5. What is a quorum and when is a quorum required?

   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. 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 on that project.

   Abstentions from voting (for reasons other than conflict of interest) do not alter the quorum and do not change the number of votes required for approval. Recusal of a member due to a conflict of interest does alter the quorum and IACUCs must ensure that the necessary number of members are present if a quorum is required.

   

6. Does the IACUC have authority over activities not supported by PHS ?

   Institutions have discretion to subject animal activities to IACUC oversight regardless of the source of funding. This practice ensures uniform standards, appropriate oversight and accountability, and therefore is often in the best interest of the institution. (See question 1 in Applicability of the PHS Policy).

   USDA requires IACUC oversight of any covered animal activity where (1) the animal has been acquired or transported by the facility, or (2) the research is being supported by any Federal funding source.

   

7. What information should be in IACUC minutes?

   PHS Policy requires that minutes of IACUC meetings, records of attendance, activities of the Committee, and Committee deliberations, be maintained by the institution. Accordingly there should be 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 recordings of meetings are not required.

   

8. May an IACUC conduct business on a teleconference call?

   Provisions for conducting convened meetings via tele- or videoconferencing are addressed in the NIH Guide for Grants and Contracts NOT-OD-06-052.

   

9. May an IACUC suspend (stop) animal activities that it did not initially approve?
   

   Yes. The PHS Policy, Guide, and the USDA Animal Welfare Regulations presume that all ongoing animal activities have received the required prospective review and approval. An activity that has been undertaken without prior approval should be halted and subsequently reported to OLAW because it constitutes serious noncompliance.

   

10. Does the Institutional Official have authority to suspend an activity that was previously approved by the IACUC, or to approve one that was not initially approved by the IACUC?

    Nothing in the PHS Policy precludes the Institutional Official or another authorized official from unilaterally suspending, terminating, or imposing sanctions on any activity involving animals, regardless of whether it was previously approved by the IACUC. However, no institutional official may approve animal activities or reinstate animal activities that were suspended by the IACUC.
    

    

11. May the institution pay or reimburse expenses incurred by nonaffiliated members?

    Nominal compensation for service on the IACUC, or reimbursement for expenses such as parking and travel costs, is generally not viewed as jeopardizing the nonaffiliated status of a member. Any compensation for participation should not be so substantial as to influence voting or reflect an important source of income. It is acceptable for the institution pay for IACUC training of nonaffiliated members (e.g., attendance at IACUC 101). [A1]

    

Institutional Reporting to OLAW

1. 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 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.

   Descriptions of program changes should be comprehensive and in sufficient detail to replace information in the currently approved Assurance.  If there are no changes then a statement to that effect must be provided.  Annual reports must represent the consensus of the Committee, and include any minority views filed by members of the IACUC.

   The report covers a 12 month time period, and is due at the end of the month immediately following the end of the institution’s reporting period.  OLAW encourages institutions to use the calendar year as the reporting period (January 1 – December 31) with the report due to OLAW January 31 for the preceding calendar year. Institutions that prefer a different 12 month reporting period may do so by indicating the preferred period in their Assurance or by notifying OLAW.  Institutions that do not select a specific reporting period will be defaulted to the calendar year and their annual report will be due January 31.
   
   See NIH Guide for Grants and Contracts NOT-OD-04-052 concerning reporting periods and annual report due dates, and http://grants.nih.gov/grants/olaw/sampledoc/report.htm for a sample annual report format.
   

   

2. 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?

   Guidance on reporting noncompliance is in the NIH Guide for Grants and Contracts NOT-OD-05-034. 
   

   

3. Should the IACUC report sanctions other than suspensions that are imposed by the Committee or by other institutional officials?

   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.   Guidance on reporting noncompliance is in the NIH Guide for Grants and Contracts NOT-OD-05-034. 
   

   

4. Are all documents submitted to OLAW subject to the Freedom of Information Act?

   The Freedom of Information Act (FOIA), 5 U.S.C.522, provides individuals with a right of access to records in the possession of the federal government.  All documents submitted to OLAW are subject to the FOIA.  However, the government may withhold information pursuant to the exemptions and exclusions contained in FOIA.

   In a ruling by the US District Court for the District of Columbia Div. No 99-3024, In Defense of Animals v. Department of Health and Human Services (HHS), 9/28/2001, the Court ruled that HHS (NIH’s parent organization) may withhold IACUC members’ names.  NIH does release the names of the IACUC Chairperson, veterinarian, and Institutional Official as reported in Assurances.

   Note also that footnote 6 in the PHS Policy allows institutions to represent the name of IACUC members other than the chair and veterinarian by using numbers or other symbols, provided there is sufficient information to allow OLAW to determine that appointees are appropriately qualified.  Identities of members must be readily ascertainable by the institution and available to OLAW upon request.
   
   In providing the facility and species inventory as part of the Assurance submitted to OLAW, institutions may identify animal areas in any manner, e.g., initials, ID number.  It is not necessary to provide OLAW with detailed diagrams of facilities or room numbers, unless specifically requested by OLAW.

   Institutions are also advised to consult the Guidance on Prompt Reporting to OLAW under the PHS Policy (NIH Guide for Grants and Contracts NOT-OD-05-034) with respect to what information is expected to be reported when reporting noncompliance.  Disciplinary documents (e.g. letters of reprimand) and correspondence between the IACUC and investigators are generally not required by OLAW, although they may be requested.

   Additional information about the FOIA, including guidelines for submitting FOIA requests, is available at:  http://www.nih.gov/icd/od/foia/index.htm

   

Protocol Review

1.  How frequently should the IACUC review research protocols?

   Under PHS Policy the maximum interval between IACUC review and approval is three years, i.e., a complete de novo review is required at least every three years.  The review must encompass all of the criteria in the Policy at IV.C.1.a.-g.  See references at A1, A2 and A6 for detailed guidance in how to satisfy this Policy requirement and the USDA requirement for annual review.  [A1, A2, A6]
   

   

2. May the IACUC administratively extend approval of a project that has expired?

   No.  IACUCs do not have authority to administratively extend approval beyond three years.  When IACUC approval expires the protocol lacks valid approval.   Continuation of animal activities in the absence of valid approval is a serious and reportable violation of PHS Policy (see NOT-OD-05-034). [A1, A6, A11]

   

3. What are the possible methods of IACUC approval?

   There are only two valid methods of IACUC review allowed by the PHS Policy: (1) full-committee review by a convened quorum of the members of the IACUC, or (2) designated member review by one or more members, employed only after all voting members have been provided an opportunity to call for full-committee review.   

   Full IACUC review may result in approval, a requirement for modifications (to secure approval), or withholding of approval.  Full committee review must occur during a convened meeting of a quorum of the IACUC members, and with a formal vote.  It is insufficient to poll each member individually in lieu of a convened quorum when using the full committee method of review.  See NIH Guide for Grants and Contracts NOT-OD-06-052 regarding use of tele- or videoconferencing when a convened meeting is required.

   Designated member review may be utilized only after all members have been provided the opportunity to call for full-committee review.  If any member requests full committee review then that method must be used.  If not, the IACUC Chairperson may appoint one or more appropriately qualified IACUC members to serve as the designated reviewer(s).  Designated review may result in approval, a requirement for modifications (to secure approval), or referral to the full committee for review.  Designated review may not result in withholding of approval.

   If a protocol is assigned more than one designated reviewer, the reviewers must be unanimous in any decision.   They must all review identical versions of the protocol and if modifications are requested by any one of the reviewers then the other reviewers must be aware of and agree to the modifications.

   The specific method of review for a given protocol must be documented, along with the outcome of the review.  [D1, A2, A5, A10, A11,] 
   

   

4. May the IACUC grant conditional or provisional approval?

   The PHS Policy recognizes that the IACUC may approve, require modifications, or withhold approval.  If the IACUC determines that a protocol is approvable, contingent on receipt of a very specific administrative modification or clarification (e.g., a contact telephone number), the Committee may handle the issue as an administrative detail that an individual (e.g., IACUC Chair or Administrator) may verify.  Requests for substantive modifications should result in the protocol coming back to the Committee.  Protocols that lack substantive information necessary for the IACUC to make a judgment (e.g.,justification for withholding analgesics in a painful procedure) should be considered incomplete and the IACUC should defer review until the requisite information is provided by the investigator. Applying descriptors, such as conditional, provisional or interim, when referring to IACUC approval is unclear, confusing, and should be avoided.  [A2, A11]

   

5. May the investigator begin animal work before receiving IACUC approval?
   
   No.

   

6. What criteria should the IACUC consider when reviewing protocols?
   

   IACUCs must confirm that:

   • the protocol is consistent with the Guide unless a scientific justification for a departure is presented and is acceptable to the IACUC;
   • the protocol conforms with the institution's Assurance;
   • the protocol will be conducted in accordance with the USDA Animal Welfare Regulations if applicable; and
   • the protocol meets the requirements of the PHS Policy at IV.C.1.a.-g.
     
     
   For further guidance, the IACUC should refer to the U.S. Government Principles.
   

   

7. Should the IACUC consider the three “Rs” of alternatives when reviewing protocols? (Refinements to research, Reduction of animal numbers, and Replacement with non-animal models)
   
   The federal mandate in U.S. Government Principle IV to avoid or minimize discomfort, distress, and pain in experimental animals consistent with sound scientific practices, is synonymous with a requirement to implement refinements (e.g., less invasive procedures or use of analgesia).  Similarly, the mandate in U.S. Government Principle III to use the minimum number of animals necessary to obtain valid results is synonymous with a requirement to reduce animal numbers.  U.S. Government Principle III further states that mathematical models, computer simulation, and in vitro biological systems should be considered, and is synonymous with a requirement to replace non-animal models wherever possible.  Thus, consideration of the three “Rs” should be incorporated into IACUC review, as well as other aspects of the institution’s program (e.g., investigator training).  [D6]
   

   

8. When institutions collaborate, or when the performance site is not the grantee institution, which IACUC is responsible for review of the research activity?
   
   See the paragraph entitled “No Requirement for Duplicate Review” in NIH Guide for Grants and Contracts NOT–OD-01-017.
   

   

9. What is considered a significant change to a project that would require IACUC review?
   
   Examples of changes considered to be significant include, but are not limited to, changes:
   
   • in the objectives of a study
   • from non survival to survival surgery;
   • resulting in greater discomfort or in a greater degree of invasiveness;
   • in the species or in approximate number of animals used;
   • in Principal Investigator;
   • in anesthetic agent(s) or the use or withholding of analgesics;
   • in the method of euthanasia; and
   • in the duration, frequency, or number of procedures performed on an animal. [A4, A7]

   Changes in personnel other than the Principal Investigator need not be considered significant 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. See NIH Guide for Grants and Contracts NOT OD-03-046. The IACUC has some discretion to define what it considers a significant change, or to establish a mechanism for determining significance on a case-by-case basis. Because significant changes require IACUC approval (using one of the valid methods described in question 3 under Protocol Review, and using the criteria described in question 6 under Protocol Review) it is critical that the IACUC clearly define and communicate to investigators its policy and mechanism for determining significance.

   

10. Is the IACUC required to review the grant application?
    
    PHS Policy and the NIH Grants Policy Statement (Part II, Terms and Conditions) require 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.  There is not an explicit requirement for the IACUC to do a side-by-side comparison of an application/proposal and the IACUC protocol.  However, institutions are responsible for ensuring that the information the IACUC reviews and approves is congruent with what is in the application/proposal. 

    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 PHS and that on the IACUC protocol is to implement a procedure for direct comparison.  Some institutions have delegated this responsibility to a particular office or position (e.g., sponsored programs or compliance office); others ask departmental chairs to verify consistency.  [A11]

    

11.  May the IACUC approve pilot studies?
    
    Yes.  Pilot studies may be appropriate to determine the technical feasibility of larger studies or to make initial assessments of the effect of procedures on animals (Guide, page 10).  Whether proposed by investigators or required by the IACUC, pilot studies require review and approval by the IACUC in accordance with the PHS Policy. 

    

12. Is the IACUC responsible for judging the scientific merit of proposals?
    

    Peer review of the scientific and technical merit of an application is considered the purview of the NIH Scientific Review Groups (SRGs), which are composed of scientific experts from the extramural research community in a particular area of expertise. However, SRGs also have authority to raise specific animal welfare concerns that can require resolution prior to a grant award.

    Although not intended to conduct peer review of research proposals, the IACUC is expected to include consideration of the U.S. Government Principles in its review of protocols. 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 PHS Policy review criteria refer to sound research design, rationale for involving animals, and scientifically valuable research. Presumably a study that could not meet these basic criteria is inherently unnecessary and wasteful and, therefore, not justifiable.
    
    The primary focus of the SRG is scientific merit and the primary focus of the IACUC is animal welfare. The two bodies have differing constitutions, mandates and functions. However, since it is not entirely possibly to separate scientific value from animal welfare some overlap is inevitable. SRGs may raise concerns about animal welfare and IACUCs may question the scientific rationale or necessity for a procedure. [ A1 ]

    

13. If an animal activity will be performed outside of the US (either by a foreign grantee or by a foreign institution as a subproject for a domestic grantee), is the grantee’s IACUC required to review and approve that activity?
    
    When the grantee is a domestic institution (i.e., domestic grant with a foreign component), PHS animal welfare requirements are applicable.  Accordingly, the grantee remains responsible for animal activity conducted at a foreign site and must provide verification of IACUC approval.  That approval certifies that the activity, as conducted at the foreign performance site, is acceptable to the grantee.   The grantee IACUC may accept, as its own, the approval of a foreign entity's IACUC; however, the grantee IACUC remains responsible for the review.  Additionally, the foreign entity must complete the “Statement of Compliance with Standards for Humane Care and Use of Laboratory Animals by Foreign Institutions” available from OLAW.  This document certifies that the institution will comply with the applicable laws, regulations, and policies of the jurisdiction in which the research will be conducted, and that the institution will be guided by the International Guiding Principles for Biomedical Research Involving Animals.

    If the grantee is a foreign institution then IACUC approval is not required.  The institution completes the Statement of Compliance referenced above.  OLAW encourages foreign institutions to use the standards in the Guide, which is available in a number of foreign translations (see http://dels.nas.edu/ilar_n/ilarhome/guide.shtml).

    

14. 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?
    
    The IACUC must review and approve activities on a project-specific basis, taking into account a number of factors, e.g., the aims of the study, consideration of alternatives, minimization of pain and distress.  For routine aspects of research (e.g., species specific techniques for immunization and titer determinations during antibody production), 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) to ensure they are up-to-date and accurate.

    

15. Is IACUC approval required for the collection of samples in foreign countries from captive wild animals or research colonies?
    
    Collection of biological samples from any live vertebrate animal for the purpose of a PHS-supported activity is covered by the PHS Policy.  If the grantee is a domestic institution, the IACUC should consider the species involved, nature of the specimens, invasiveness of the procedure, risks to personnel, and qualifications of the individual(s) taking the sample(s).  (For further information concerning foreign performance sites see question 13 under Protocol Review.) 

    Grantee institutions should also consult with other agencies of the federal government as appropriate, e.g., US Fish and Wildlife Service, USDA-APHIS-Veterinary Services, and the CDC for specimen importation requirements.   [A7]
    

    

16. 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?
    
    Although animals used as sentinels, breeding stock, blood and blood product donors, or for other similar purposes may not be part of specific research protocols, their use is part of the institutional research program and directly supports research activities.  Consequently, the IACUC should review protocols and SOPs that involve animals for such purposes, initially and at appropriate intervals (at least once every three years).  [A4]

    

17. What guidelines should IACUCs follow for fishes, amphibians, reptiles, birds, and other nontraditional species used in research?

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 can generally be adapted to the care and use of various kinds of nontraditional research animals.  IACUCs may seek the advice of experts when necessary, and refer to scientific-based publications prepared by professional organizations with interest in various species.  Appendix A of the Guide references many such publications.  [A7]

Program Review and Inspection of Facilities

1. Should the IACUC inspect laboratories or other sites where investigators use animals?
   

   Institutions are responsible for oversight of all animal-related activities regardless of how long or where the activity occurs.   Satellite facilities (defined by PHS Policy as a containment outside a core or centrally managed area in which animals are housed for more than 24 hours) and areas where any form of surgical manipulations (minor, major, survival, non-survival) are performed must be inspected at least once every six months by the IACUC as part of the semiannual evaluation.  Institutions have discretion with regard to how they oversee areas used for routine weighing, dosing, immunization, or imaging, but should monitor such areas on a random or fixed schedule to effectively oversee activities at the institution.  USDA requires semi-annual inspection of “animal study areas” defined as areas where USDA covered animals are housed for more than 12 hours.   [A1, A7]

   

2. How does the IACUC distinguish between significant and minor deficiencies?
   

   PHS Policy requires the IACUC to make this distinction in its semiannual reports to the Institutional Official.   A significant deficiency is defined as one which is or may be a threat to the health or safety of animals.   Examples include inoperable HVAC, electrical or watering systems, failure of such systems sufficient to affect critical housing and operational areas, and situations such as natural disasters that cause injury, death, or severe distress to animals.  Significant program deficiencies can result from an institution's failure to fully understand or implement some aspect of its animal care and use program required by the PHS Policy, or failure to function according to commitments made in its Assurance, and may reach the level of reportable noncompliance.  Generally, a minor deficiency refers to a problem for which an immediate solution is not necessary to protect life or prevent distress (e.g., peeling or chipped paint).  Ongoing inattention to a minor deficiency may result in a chronic problem indicative of a programmatic failure and may constitute a significant deficiency.  [A7]

   

3. May the IACUC use an AAALAC inspection as its semiannual evaluation?

   See paragraph entitled “Utilization of AAALAC activities as Semiannual Program Evaluation” in the NIH Guide for Grants and Contracts NOT OD-00-007.

   

4. Is the IACUC required to inspect field study sites?  

   While semiannual IACUC inspections of field study sites are not required and in many circumstances are impractical, IACUCs should be apprised of the circumstances under which studies are conducted so that they can consider risks to personnel, and impact on study subjects. This may be partially accomplished by written descriptions, photographs, or videos that document specified aspects of the study site. The IACUC should also ensure that appropriate permits are in place. USDA animal welfare regulations exempt areas containing free-living wild animals in their natural habitat from inspection [See 9 CFR, Part 2, Section 2.31(c)(2)].

   

Animal Use and Management

1. Is the use of carbon dioxide an acceptable euthanasia agent?
   
   Although CO2 is generally considered an acceptable euthanasia agent for small animals when properly administered, its acceptability is predicated on a number of critical factors that are delineated in the NIH Guide for Grants and Contracts NOT-OD-02-062.

   

2. Is the IACUC responsible for tracking animal usage?
   

   Although the PHS Policy does not explicitly require a mechanism to track animal usage by investigators, it does require that proposals specify a rationale for the approximate number of animals to be used and be limited to the appropriate number necessary to obtain valid results. 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. Monitoring should not exclude the disposition of animals inadvertently or necessarily produced in excess of the number needed or which do not meet criteria (e.g., genetic) established for the specific study proposal. Institutions have adopted a variety of administrative, electronic, and manual mechanisms to meet institutional needs and PHS Policy requirements. [A7

   

3. May an investigator transfer animals and research to an institution different than the grantee institution? 
   

   The transfer of PHS-supported research to a different institution requires the prior approval of the funding component. The proposed new grantee institution must have or obtain an Animal Welfare Assurance and possess all the resources necessary to fulfill the conditions of the grant, and its IACUC must review and approve the animal activities. The original IACUC approval is void when the original grantee formally relinquishes the award. The receiving institution must provide verification of IACUC approval prior to receiving funding. Note that the conditions of approval by the IACUC at the receiving institution may differ from those required by the original grantee’s IACUC.

   

4.  May investigators use non-pharmaceutical grade compounds in animals?
   
   OLAW and USDA consider that the use of non-pharmaceutical grade compounds should be based on:

   • scientific necessity;
   • no availability of an acceptable veterinary or human pharmaceutical-grade compound; and
   • specific review and approval by the IACUC.
     
   
   Investigators and IACUCs should consider relevant animal welfare and scientific issues including safety, efficacy, and the inadvertent introduction of new variables. 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 non-survival studies, the scientific issues remain the same and the principles and need for professional judgment outlined above still apply. [A11]

   

5. May investigators use expired pharmaceuticals, biologics, and supplies in animals? 

   The use of expired pharmaceuticals, biologics, and supplies is 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 that such use would not negatively impact animal welfare or compromise the validity of the study.  The veterinarian and IACUC must maintain control over the use of expired medical materials in order to meet their responsibilities to avoid or minimize discomfort, pain or distress to animals. 

   

6. How can institutions assure animal welfare when HVAC systems malfunction or fail?
   

   Institutions that conduct PHS -supported research, testing, or training have a responsibility to ensure animal welfare and an obligation to protect the federal investments in these activities. The Guide provides recommendations regarding temperature, humidity, and ventilation for common laboratory animals and briefly discusses parameters regarding heating, ventilating, and air conditioning (HVAC) that need to be considered. It also states “In the event of a partial HVAC system failure, systems should be designed to supply facility needs at a reduced level. It is essential that life-threatening heat accumulation or loss be prevented during mechanical failure.” (Guide , pages 75-76)
   
   Monitoring HVAC equipment performance is important to ensure timely identification of local or regional power disruptions or system malfunctions. Institutions are strongly encouraged to consider using available electronic technology to measure temperature in each animal room on a continuous basis. Appropriately installed and powered sensors and electronic alarm systems can rapidly notify maintenance and animal care staff of the need to take immediate action to prevent harm to animals. Sole reliance on employees to identify changes in animal room conditions or the use of high-low thermometers to track changes in temperature may not be sufficient to allow timely intervention and prevent catastrophic loss.
   
   The Guide also recommends that institutions develop disaster plans that take into account both personnel and animals. Such plans should consider HVAC and alarm malfunctions, as well as failures in primary and emergency power sources, mechanisms for maintaining appropriate temperatures and ventilation, and a scheme for relocating animals when power cannot be restored or repairs effected promptly. Designations of responsibilities, consideration of personnel absences, training, and institutional policies and procedures are important aspects of a disaster plan.

   The same requirements apply to fishes, amphibians, and other vertebrates whose environment is aquatic, the emphasis being on water temperature and quality, including oxygenation, circulation and filtration.
   
   OLAW provides a Disaster Planning and Response Resources web page to assist institutions in planning and responding to natural and other disasters affecting animal facilities.

   

7. What are the requirements for conducting rodent survival surgery?

   In accord with the Guide, the species of animal influences the components and intensity of the surgical program and modification of standard techniques might be desirable or even required, but should not compromise the well-being of the animals. It further notes that some characteristics of common laboratory-rodent surgery, such as smaller incision sites, fewer personnel in the surgical team, manipulation of multiple animals at one sitting, and briefer procedures, can make modifications in standard aseptic techniques necessary or desirable. For most rodent surgery, a facility may be small and simple, such as a dedicated space in a laboratory appropriately managed to minimize contamination from other activities in the room during surgery. (Guide, pages 63 and 78)
   

   

8. Is the mouse ascites method an acceptable method of monoclonal antibody production? 

   The NIH concurs with the findings and recommendations in the 1999 report of the National Research Council Monoclonal Antibody Production which indicates that during the accumulation of ascites there is likely to be pain and distress, particularly when some cell lines that are tissue-invasive are used and in situations of significant ascites development.  The Report concluded that there is and will continue to be scientific necessity for this method, but that as tissue-culture systems are further developed, tissue-culture methods for the production of monoclonal antibodies should be adopted as the routine method unless there is a clear reason why they cannot be used. 

   Accordingly, IACUCs are expected to critically evaluate the proposed uses of the mouse ascites method.  Prior to approval of such protocols 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. [D6]

   

9. Are major multiple survival surgical procedures permitted on a single animal?

   The Guide discourages multiple major survival surgical procedures on a single animal but provides that if scientifically justified by the user and approved by the IACUC they may be permitted.  Guide examples of justifications include (1) procedures that are related components of a research project; (2) conservation of scarce animal resources, and (3) clinical necessity.  The Guide does not consider cost savings alone an adequate reason for performing major multiple survival surgical procedures.  [A7]
   
   Note that under the AWA regulations, major multiple survival surgical procedures are permitted only if the multiple procedures are included within one proposal, justified for scientific reasons, and approved by the IACUC.   The AWA requires prior authorization of the USDA Administrator, Animal and Plant Health Inspection Service, for an exemption from this requirement.  [See 9 CFR, Part 2, Section 2.31 (d)(1)(x)]

   

10. May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density?

    OLAW supports the Guide’s approach to applying performance standards to achieve specified outcomes, and expects institutions to use the Guide’s engineering standards as a baseline.  The Guide clearly states that the need for adjustments to the recommendations for primary space enclosures should be made at the institutional level by the Institutional Animal Care and Use Committee (IACUC) and should be based on performance outcomes.  The Guide further identifies examples of performance indices to assess adequacy of housing, including health, reproduction, growth, behavior, activity, and use of space (Guide, pages 25-26).  IACUC determinations of the need for adjustments in the space recommendations should be based on veterinary considerations or scientific justification relative to the nature of the protocol and its requirements.    Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non animal welfare considerations are not acceptable.  IACUC approved deviations from the Guide must be clearly documented and reflect the scientific or veterinary justification relevant to the action. 

    For example, the Guide notes that space allocations should be reviewed and modified as necessary to address individual housing situations and animal needs such as prenatal and postnatal care.  One way to address housing for maternally dependent litters of mice and rats is to consider them as single entities with their  parent(s) until the pups begin actively moving about the cage, at which point multiple parental/litter groups should then be housed according to housing conditions recommended in the Guide.

    

Institutional Responsibilities

1. What kind of training is necessary to comply with PHS Policy, and how frequently should it be provided?

   The institution is responsible for the training of its staff.  The size and nature of institutional research programs varies significantly and accounts for the corresponding variation in the scope and depth of instructional programs and the frequency at which they are offered.
   
   At a minimum, the PHS Policy and Guide require 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;
   • 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;
   • provide training or instruction in research and testing methods that minimize the number of animals required to obtain valid results and minimize animal distress;
   • 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; and
   • ensure compliance with any initial and continuing education regarding State requirements for the licensing of veterinary or animal health technicians.   [A4]

   

2. What is required for an occupational health and safety program?
   
   The Guide states that “An occupational health and safety program must be part of the overall animal care and use program” and provides an outline of the principal requirements for such a program.  Institutional research programs vary regarding the species used, the potential hazards presented, and the biological, chemical, or physical agents employed in research.  Thus, the institution must base its health program on an assessment of the risks present in its particular animal research and support program.

   Risk assessment and the implementation of health programs 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.  Guidance regarding basic health program elements, recommendations concerning zoonoses surveillance and prophylactic immunizations, and advice on which categories of personnel to include in light of potential exposure to risks is provided in the reference at A4.

   Institutions should make clear that personal medical records are confidential documents and ensure that their contents are treated appropriately.  To avoid placing individuals and institutions at risk, prior clearance to work in specific areas or conduct specific activities can be provided by safety and health, biosafety, and/or radiation safety professionals.  If individuals decline to participate in the health program, institutions can restrict their participation to activities that pose no
   identified occupational health-related risks as determined by a health professional.  [A4]

   See the NRC publication Occupational Health and Safety in the Care and Use of Research Animals for additional information.
   

   

3. Do grantee institutions need animal facility disaster plans?
   
   The requirement for institutional disaster planning is found in the Guide (p. 46) which states “A disaster plan that takes into account both personnel and animals should be prepared as part of the overall safety plan for the animal facility.”    See OLAW’s Disaster Planning and Response Resources.  [A9]

   

4. What kind of administrative organization works best for ensuring compliance?

   Direct, clear and straight forward lines of responsibility and corresponding authority function well and allow organizations to respond quickly and effectively when necessary.  Key components in such organizations are the Institutional Official (IO), the IACUC, and the attending 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 and occupational health.  The IACUC, appointed by the organization's chief executive officer, reports directly to the IO and is empowered to perform its duties without undue interference. It is recommended that the veterinarian 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, and the Guide. [A2]

   

5. What is the difference between the Institutional Official and the Chief Executive Officer?

   The Institutional Official (IO) signs the Assurance and is the person in the organization with the administrative and operational authority to commit institutional resources to ensure that the animal care and use program will comply with the requirements of the PHS Policy.  The PHS Policy requires the chief executive officer (CEO) to appoint the IACUC in accord with specified qualifications and membership criteria, although the CEO may delegate this authority in writing.  In some institutions, the IO 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. [A7]

   

6. Is post approval monitoring required?

   Monitoring of animal care and use is required, though neither the PHS Policy nor the Guide explicitly address or require specific or separate post approval monitoring (PAM) procedures to compare the practices described in approved protocols and SOPs against the manner in which they are actually conducted.

   IACUCs are charged, however, with program oversight and as such are responsible for program evaluations, reviews of protocols, reporting noncompliance, ensuring that individuals who work with animals are appropriately trained and qualified, and addressing concerns involving the care and use of animals at the institution. The veterinarian with program authority and responsibility for animal activities along with the animal care and technical staff, add another important level of program supervision.

   Related components of institutional programs provide monitoring by a multi-disciplinary team of individuals.  Examples of such components include daily observation of animals by trained animal care personnel and communication to the veterinary staff for follow-up, facility monitoring by facility maintenance personnel, post operative care by trained personnel, evaluation of outcomes of animal procedures by investigators and staff, hands-on training in animal procedures, and appropriate reporting of incidents involving occupational health and safety.  All of these functions and responsibilities imply a level of monitoring.  Ultimately the institution has flexibility in how it achieves compliance. 

   Some institutions have developed PAM programs with dedicated staff that physically monitor procedures and practices associated with animal use protocols. This is one acceptable method that institutions may elect to adopt, but it is not a federally mandated requirement.  Whatever methods an institution incorporates, it is important that the authority and responsibility of the IACUC not be contravened by a PAM program, institutional compliance officials, or other mechanism established to monitor animal care and use.

   

7. May institutions utilize the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (Ag Guide) if their programs include traditional farm animals?

   PHS Policy mandates that institutions use the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for developing and implementing a program for activities involving animals.  The Guide states that it “…applies to farm animals used in biomedical research, including those maintained in typical farm settings.”  It further emphasizes that the use of farm animals in research should be subject to the same ethical considerations as the use of other animals in research.  (Guide, page 4)

   The Ag Guide primarily refers to agricultural animals used in agricultural research for which the scientific objectives are to improve understanding of the animals’ use in production agriculture.  It is therefore inappropriate to substitute the Ag Guide for the Guide based on the species of animal.  However, there may be circumstances where it is appropriate to follow the standards of the Ag Guide in biomedical research (e.g., transmission studies of avian influenza under simulated or actual (commercial) poultry production conditions).  Proposals to conduct such activities should be reviewed on a case by case basis and any approval to depart from provisions of the Guide must be based on scientific justifications acceptable to the IACUC.

   

REFERENCES  

• Please send email to mailto:GWAS@mail.nih.gov.