Key Dates

Related Announcements

NOT-OD-12-148 - Guidance on Departures from the Provisions of the Guide for the Care and Use of Laboratory Animals

NOT-OD-19-136 - Report on Reducing Administrative Burden for Researchers: Animal Care and Use in Research

Issued by

Office of The Director, National Institutes of Health (OD)

Purpose

Through this Request for Information (RFI), the NIH Office of Laboratory Animal Welfare (OLAW) is seeking input on clarifying guidance to Assured institutions regarding the Institutional Animal Care and Use Committee (IACUC) reporting requirements for departures from the Guide for the Care and Use of Laboratory Animals (Guide).

Background

The 21^st Century Cures Act, Section 2034(d), directed the NIH to conduct a review of applicable regulations and policies for the care and use of laboratory animals and to make revisions, as appropriate, to reduce administrative burden on investigators while maintaining the integrity and credibility of research findings and protection of research animals. The public identified departures from the Guide as an area to reduce administrative burden by eliminating the Public Health Service (PHS) requirement for compliance with the Guide. Because the PHS Policy on the Humane Care and Use of Laboratory Animals (Policy) IV.A.1. requires institutions to use the Guide as a basis for developing and implementing an institutional program for activities involving animals, the requirement for adherence to the Guide remains in effect for Assured institutions. The PHS Policy IV.B.3. requires, among other things, that semiannual reports to the Institutional Official (IO):

• contain a description of the institution's adherence to the Guide and the PHS Policy,
• identify any departures from the Guide and the PHS Policy, and
• state the reasons for each departure.

IACUC-approved departures from the Guide must be based on scientific, veterinary medical, or animal welfare issues. The PHS Policy IV.F.3. requires that Assured institutions report noncompliant, unapproved departures from the Guide to OLAW.

The public also recommended that deviations from should statements no longer be considered departures and therefore, not be reportable. The PHS Policy incorporates by reference the Guide, which is a widely accepted and respected primary reference on animal care and use, written by the Institute for Laboratory Animal Research of the National Academy of Sciences. It provides the best practice standards for biomedical animal care and use programs. The purpose of the Guide is to assist institutions in caring for and using animals in a scientifically, technically, and humanely appropriate manner. It also assists investigators in fulfilling their obligation to plan and conduct animal experiments according to the highest scientific and ethical principles. Recommendations in the Guide, including should statements, are based on published data, scientific principles, expert opinion, and experience with methods and practices that have proven to be consistent with both high-quality research and humane animal care and use. These recommendations should be used as a foundation for the development of a comprehensive animal care and use program, recognizing that the concept and application of performance standards, according to the goals, outcomes, and considerations defined in the Guide, are essential to this process. In the report Reducing Administrative Burden for Researchers: Animal Care and Use in Research, developed in response to the 21^st Century Cures Act, OLAW committed to clarifying the guidance for the reporting requirements of departures from the Guide.

The provisions of the Guide are stated as standards that:

• must be met, which OLAW considers are minimum standards required of all Assured institutions,
• should be met, which indicate a strong recommendation for achieving a goal, and
• may be met, which indicate a suggestion to be considered.

The Guide is written in general terms so that its recommendations can be applied across diverse institutions and settings. It encourages a balance of engineering and performance standards, setting a target for optimal practices, management, and operations while encouraging flexibility and judgment, if appropriate, based on individual situations. This approach requires that users, IACUCs, veterinarians, and technicians apply professional judgment in making decisions regarding animal care and use.

Information Requested

The NIH is seeking input on the following:

1. Guide Exceptions list
2. Guide Must Statements checklist
3. IACUC reporting requirements in the Guide

The NIH is seeking input on the following clarifications to IACUC reporting requirements for departures from must, should, and may statements in the Guide.

Reporting to the Institutional Official (IO) in the semiannual report is not required for:

1. Deviations from may statements in the Guide.
   May statements in the Guide are suggestions that institutions choose to implement if suitable for their program. Deviations are not reported in the semiannual report to the IO.
    
2. A specifically described Guide exception from a should statement.
   The Guide establishes exceptions for specific should statements, which are not departures from the Guide. There are no Guide exceptions for must statements. Exceptions are not reported in the semiannual report to the IO.

   Example: A PI requests single housing for her rats to measure individual urine output post-treatment with a test article. After considering the specific details of the proposed experiment, the IACUC approves the protocol.

• Guide: “Social animals should be housed in stable pairs or groups of compatible individuals unless they must be housed alone for experimental reasons or because of social incompatibility” (p 51).
• Discussion: This is a deviation from a should statement according to a specifically established exception in the Guide (experimental reasons). Exceptions are not departures from the Guide and need not be reported in the semiannual report to the IO. 

3. Deviations from a should statement in the Guide using established performance standards.

   OLAW and the Guide advocate using outcome-based performance standards by applying professional judgement and experience to should statements to ensure humane animal care and use. Performance standards can only be applied to should statements. They cannot be applied to must statements.

   A performance standard means a standard or guideline that, while describing a desired outcome, provides flexibility in achieving this outcome by granting discretion to those responsible for managing the animal care and use program, the researcher, and the IACUC. The performance approach requires professional input, sound judgment, and a team approach to achieve specific goals. Performance standards can be advantageous because they accommodate the consideration of many variables, such as the species and previous history of the animals, facilities, staff expertise, and research goals, to optimize animal welfare. Implementation of performance standards allows the recommendations of the Guide to be tailored to meet unique needs of the research and the animal care and use program. Performance standards are one of the most important components of the infrastructure of PHS oversight of animal programs at Assured institutions. They can be applied to virtually any area of animal care and use, including veterinary care, environmental enrichment, training, exercise, and housing.

   Development and validation of performance standards need not be complex and should objectively determine the appropriate assessment outcomes using data and facts. Institutions that do not currently have performance standards that meet the following criteria are expected to use the benchmarks provided by the Guide to develop performance-based policies and procedures. A performance standard should:

   • • support scientific objectives,
     • support the health and welfare of the animals,
     • include a justified performance index, and
     • have associated outcome criteria.

   The National Academy of Sciences workshop Design, Implementation, Monitoring and Sharing of Performance Standards for Laboratory Animal Use summarized the following important considerations. When developing a performance standard, it is essential to first clearly define the desired outcomes and goals (p 7). This can involve conducting a review of the current literature and industry best practices to identify appropriate performance measures to evaluate the alternative method (p 54). The IACUC should compare the alternative approach to the Guide recommendations by critically evaluating the objective measures of outcome-based performance and identifying performance indices to assess the adequacy of the performance standard while ensuring that it does not negatively impact animal well-being. The IACUC then reviews and requires revisions as needed. Once the IACUC is satisfied with the revisions and allows implementation of the performance standard, a plan is developed to regularly monitor the established performance outcome.

   Example 1: A PI proposes to forgo cage sanitization for a 5-week study because mice are exposed to a biohazardous infectious agent. A standard operating procedure (SOP) was developed based on data collected at the institution addressing species, cage density, parameters for sanitary conditions, regular ammonia level testing, and use of specialized bedding that facilitates cleanliness. Both the SOP and protocol were reviewed and approved by the IACUC.

   • Guide: “Sanitization of enclosures and accessories, such as tops, should be performed at least once every 2 weeks” (p 70).
   • Discussion: This is a deviation from a should statement that follows a performance standard using data established at the institution, is not a departure from the Guide, and is not reported in the semiannual report to the IO.

   Example 2: All mouse wire bar lids are sanitized once every 4 weeks according to performance standards established by the institution. The SOP was reviewed and approved by the IACUC.

   • Guide: “In general, enclosures and accessories, such as tops, should be sanitized at least once every 2 weeks” (p 70).
   • Discussion: This is a program-wide institutional, rather than a study-specific deviation from a should statement that follows a performance standard using data established by the institution. It is not a departure from the Guide and is not reported in the semiannual report to the IO.

Reporting in the semiannual report to the IO is required for:

1. An IACUC-approved deviation from a must statement in the Guide.
   Example: The PI proposes to confine dogs for 3 days in small cages to limit the dogs’ ability to stand as part of a scientifically justified research requirement. The IACUC reviews and approves the scientific justification and the protocol.

• Guide: “At a minimum, animals must have enough space to express their natural postures...” (p 56).
• Discussion: This is a deviation from a must statement of the Guide that has been scientifically justified by the PI and reviewed and approved by the IACUC. It is an approved departure and must be reported in the semiannual report to the IO.

2. An IACUC-approved deviation from a should statement without a specifically described Guide exception and lacking established performance standards.
   Example: In describing a food-restricted mouse study, the PI stated that animals must be anesthetized before weighing. The PI cited data demonstrating the adverse effect of anesthesia on the animals’ performance of behavioral tasks required in the proposed study. The research team proposed to monitor and weigh the animals and requested permission to weigh monthly rather than weekly. The IACUC reviewed and approved the request.

• Guide: Regarding food-restricted diets: “Body weights should be recorded at least weekly” (p 31).
• Discussion: This is a deviation from a should statement based on a scientific justification that has been reviewed and approved by the IACUC. It is an approved departure from the Guide and must be reported in the semiannual report to the IO.

Reporting to OLAW is required for:

1. Deviations from a must statement in the Guide without IACUC approval.
   Example: The IACUC learns that one of the satellite facilities has inadvertently been omitted from the disaster plan.

• Guide: “Facilities must therefore have a disaster plan” (p 35).
• Discussion: This is a noncompliance. The IACUC must report to OLAW through the IO and develop a plan and schedule to correct this unapproved deviation from a must statement in the Guide.

2. Deviations from a should statement when:
    
   1. Not based on a specifically described Guide exception, or
      Example: The IACUC approved a PI’s protocol allowing the research team to sanitize solid-bottom rodent cages weekly in a satellite facility. The PI goes on sabbatical and the research team decides that sanitation every 3 weeks is sufficient. A post-approval monitor discovers the discrepancy and informs the IACUC.

• Guide: “In general, enclosures and accessories...should be sanitized at least once every 2 weeks. Solid-bottom caging... usually require[s] sanitation at least once a week” (p 70).
• Discussion: This is a noncompliance. The IACUC must report to OLAW through the IO and develop a plan and schedule to correct this unapproved deviation from a should statement in the Guide.

2. Not based on an established performance standard, or
   Example: An institution has begun a breeding program for Siberian hamsters, a new species at the institution. The visiting investigator who was charged with setting up the breeding program assured the IACUC members that the species does well with trio breeding. The IACUC approved the protocol without considering that the facility’s cages have 20 inches² of floor space or consulting the investigator, veterinarian, or the literature regarding space requirements.

• Guide: “The space recommendations presented here are based on professional judgement and experience. They should be considered the minimum for animals housed under conditions found in laboratory animal housing facilities” (p 56 and Table 3.2).
• Discussion: This is a noncompliance. Breeding in space that did not meet Guide standards was permitted without appropriate justification or use of an established performance standard regarding space requirements. The IACUC must report to OLAW through the IO and develop a plan and schedule to correct this unapproved deviation from a should statement in the Guide.

• 3. Not IACUC approved
     Example: The PI for a guinea pig study is trying to cut costs and instructed his laboratory manager to order non-pharmaceutical-grade euthanasia drugs for his study. The original animal activity approved by the IACUC specified pharmaceutical grade drugs and the PI did not submit an amendment to the IACUC requesting the change.

• Guide: “The use of pharmaceutical-grade chemicals and other substances ensures that toxic or unwanted side effects are not introduced into studies conducted with experimental animals. They should therefore be used, when available, for all animal-related procedures. The use of non-pharmaceutical-grade chemicals or substances should be described and justified in the animal use protocol and be approved by the IACUC” (p 31).
• Discussion: This is a noncompliance because it is a change that was not approved by the IACUC in advance of implementation, and therefore constitutes a deviation from an IACUC-approved protocol. The IACUC must report to OLAW through the IO and develop a plan and schedule to correct this unapproved deviation from a should statement in the Guide.

Additional Resources

Please see OLAW’s webpage: Departures from the Guide.

How to Submit a Response

Comments must be submitted electronically on the RFI webpage. Comments must be received on or before November 1, 2021, at 11:59 PM ET. The comments may be made available on the OLAW website.

Responses to this RFI are voluntary and may be submitted anonymously. Please do not include any personally identifiable or other information that you do not wish to make public. Proprietary, classified, confidential, or sensitive information should not be included in responses. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements. This RFI is for informational and planning purposes only and is not a solicitation for applications or an obligation on the part of the Government to provide support for any ideas identified in response to it. Please note that the Government will not pay for the preparation of any information submitted or for use of that information.

Inquiries

Please direct all inquiries to:

Office of Laboratory Animal Welfare
Telephone: 301-496-7163
Email: [email protected]