|Policy & Guidance|
|Compliance & Oversight|
|Research Involving Human Subjects|
|Office of Laboratory Animal Welfare (OLAW)|
|Animals in Research|
|Peer Review Policies & Practices|
|Guidance for Reviewers|
|Intellectual Property Policy|
|Acknowledging NIH Funding|
|Invention Reporting (iEdison)|
|NIH Public Access|
The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Policy) requires that Assured institutions base their animal care and use programs on the Guide for the Care and Use of Laboratory Animals (Guide). The Office of Laboratory Animal Welfare (OLAW) is the National Institutes of Health (NIH) office responsible for the administration and coordination of the PHS Policy. In December 2010, the National Academies Press released the 8th Edition of the Guide (PDF) , copyrighted 2011, to update the 7th Edition of the Guide that had been published in 1996.
The NIH adopted the 8th Edition of the Guide effective January 1, 2012. In OLAW's judgment, the 8th Edition of the Guide empowers continued advancement in the humane care and use of vertebrate animals in research, research training, and biological testing.
OLAW prepared Position Statements in response to public concerns. The Statements clarify how OLAW expects Assured institutions to implement the 8th Edition of the Guide, emphasize OLAW's continuing support for performance standards, restate policies that remain unchanged, and endorse several changes that will improve animal welfare.
OLAW requires Assured institutions to base their programs of animal care and use on the 8th Edition of the Guide as of January 1, 2012. Assured institutions must complete at least one (of the two that are required) semiannual program review and facility evaluation using the 8th Edition of the Guide as the basis for evaluation by December 31, 2012. It is not required that all necessary changes be completed by December 31, 2012, but rather that an evaluation must be conducted and a plan and schedule for implementation of the 8th Edition of the Guide must be developed by December 31, 2012.
In addition to requiring that Assured institutions base their animal care and use programs on the Guide, the PHS Policy directs that institutions must identify specifically any departures from the provisions of the Guide and state the reasons for each departure. (See PHS Policy IV.B.3.) OLAW considers a “must” statement in the Guide to be a minimum standard required of Assured institutions. The Institutional Animal Care and Use Committee (IACUC) must review and approve departures from the minimum standards of the Guide. IACUC approval must be based on scientific, veterinary medical, or animal welfare issues. Cost saving or convenience alone is not sufficient justification to approve a departure from the minimum standards of the Guide.
“Should” statements in the 8th Edition of the Guide often involve performance standards. OLAW supports and has a high regard for performance standards developed by the research community. OLAW does not consider established performance standards to be a departure from the Guide. A well-established performance standard meets the following criteria:
Institutions that have well-developed policies and procedures that meet the above criteria may not have to adjust those policies and procedures as part of their implementation of the 8th Edition of the Guide.
An institution may elect to follow a different course of action than a “should” statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC. In addition, institutions are not required to comply with “should” statements that do not apply to their program. The OLAW Semiannual Program Review and Facility Inspection Checklist (Checklist) sample document has been updated to meet the standards of the 8th Edition of the Guide and now includes a “Not Applicable” (NA) column. Use of the Checklist is not required; it is provided for the convenience of Assured institutions. For IACUCs that choose to use the Checklist, appropriate selection of NA is sufficient documentation that the IACUC has considered a standard and determined that it is not applicable to their program.
The 8th Edition of the Guide further develops the concept and advocates the use of outcome-based performance standards (See inset.) that were a basis of the 7th Edition of the Guide.
|“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... so that implementation can be best tailored to meet the recommendations in the Guide.” (See Guide pages 6-7.)|
Performance standards are the most important component of the infrastructure of PHS oversight of animal programs at Assured institutions. IACUCs are able to meet their responsibility to ensure humane animal care and use while advancing quality scientific research through the use of performance standards in their oversight of institutional animal programs. OLAW encourages the cooperative application of diverse expertise to develop outcome-based performance standards that enhance the quality of animal care and use programs. OLAW expects Assured institutions to apply appropriate professional judgment and experience to the challenges inherent in developing policies and procedures to maintain a quality program that provides humane care to vertebrate animals.
Implementation of the Guide is expected to have a minimal impact on institutions that are currently using policies and procedures based on well-developed performance standards. These policies and procedures may not need to be revised as part of the institution's implementation of the 8th Edition of the Guide.
A well-established performance standard meets the
Institutions that do not currently have performance standards that meet the criteria stated in this document (See inset.) are expected to use the benchmarks provided by the 8th Edition of the Guide to develop performance-based policies and procedures.
The 8th Edition of the Guide includes standards based on best practices. These standards, developed within the research community itself, reflect efforts to improve vertebrate animal welfare through self-monitoring and the application of outcome-based performance standards in striving for better animal care and use that benefits scientific research. Not all practice standards have been published in the literature. In addition to referencing the published literature, the Guide also captures information based on the experience of biomedical researchers, veterinarians, and IACUC members. (See Guide page 7.) As such, many institutions have developed, and therefore already instituted, the policies and procedures described in the 8th Edition of the Guide.
The following Position Statements describe the ways in which OLAW expects institutions to implement the 8th Edition of the Guide. In May 2012, OLAW updated the original (December 2011) Position Statements following an analysis of the public's comments on their understanding of the Position Statements. In response to those comments, OLAW clarified Position Statements: 1) Cost, 2) Housing, 2a) Nonhuman Primate Housing, 2c) Rodent Housing, and 3) Non-Pharmaceutical-Grade Substances. For a summary of changes, see the May 2012 Update Summary (PDF - 52 KB). For reference, an archive of the original version is available for download at December 2011 Position Statements (PDF - 100 KB). Clarification was also added to the related OLAW FAQs: G11, F16, F14, F10, and F4.The solicitation for public comments on the Position Statements was held from December 1, 2011 to February 3, 2012. Forty-four individuals and organizations responded. (View the comments.) Twenty-six responses were from those who identified themselves as individuals, 6 were from PHS Assured institutions, 2 were from animal advocacy organizations and 9 were from professional organizations.
Animal welfare and the integrity of research findings, rather than cost alone, should be the primary factors in decisions related to assuring compliance with the recommendations in the Guide in PHS-funded research. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle II.) Assured institutions are responsible for compliance with the Guide. OLAW believes compliance can be best accomplished using teamwork, professional judgment, and experience. The PHS Policy and the Guide define the minimum standards (“musts”) and performance standards (“shoulds”) that OLAW expects of Assured institutions. OLAW recognizes that there are many ways to achieve humane animal care and use. An institution may use an alternative approach if the approach satisfies the requirements of the PHS Policy as determined by OLAW. In many instances, institutions and IACUCs elect to exceed the standards. This is not required and can add expense to the program. OLAW does not discourage or encourage institutions from exceeding the standards.See also OLAW FAQ G11: May cost be used as justification for not implementing animal welfare standards?
OLAW concurs with the Guide that performance standards are to be applied to housing issues. (See Guide pages 50-63.) Outcome-based performance standards are paramount when evaluating cage or pen space for housing animals used for research, research training, and biological testing. While the Guide's space recommendations are accepted reference points for addressing space needs, performance standards allow flexibility to improve animal welfare and scientific research. An institution's animal housing practices must be species-specific, appropriate for the animals, and in compliance with all applicable federal and local regulatory requirements.See also OLAW FAQ F16: May performance standards determine housing issues?
Like all social animals, nonhuman primates should be socially housed. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle VII and 9 CFR Ch. 1, Part 3, Subpart D.) Staff performing the socialization should be trained and competent in the procedure and knowledgeable about the animals. Behaviorally compatible animals should be used whenever possible in socialization attempts. Group composition is critical and numerous species-specific factors should be taken into consideration when forming a group. Due to conformational differences of animals within groups, more space or height may be required to meet the animals' physical and behavioral needs. Determination of the appropriate cage size is not based on body weight alone. Professional judgment is paramount in making such determinations. (See Guide pages 58-61.)
Compliance with the USDA regulations is an absolute requirement of this [PHS] Policy. (See PHS Policy footnote 2.) The Animal Welfare Act, 7 USC Section 2143, requires regulated facilities to provide an environment adequate to promote the psychological well-being of primates. The Animal Welfare Regulations (AWR), 9 CFR 3.81, require regulated facilities to document and follow an appropriate plan for environmental enhancement adequate to promote the psychological well-being of nonhuman primates. The plan must be in accordance with currently accepted professional standards as cited in appropriate professional journals or reference guides, and as directed by the attending veterinarian. It must address, at a minimum, the areas of Social Grouping, Environmental Enrichment, Special Considerations, Restraint Devices, and Exemptions. In regards to Social Grouping, 9 CFR 3.81(a) requires that regulated facilities meet the social needs of nonhuman primates that are known to exist in social groups in nature. This requirement has only three specified exceptions, allowing separate, individual housing for animals that are overly aggressive or debilitated, that require isolation because they have contagious diseases, or that are incompatible with all other animals. Exemptions to all or part of the overall plan to promote psychological well-being are also allowed, under 9 CFR 3.81 (e)(1) and (2), for specific veterinary reasons, as directed by the attending veterinarian, or for strong scientific reasons, as outlined in a research proposal approved by the IACUC. In most cases, based on currently accepted professional standards, such as the Guide, group housing is the most appropriate method of ensuring that the animals' social needs are met. Protected tactile contact is considered single housing by the USDA, with rare exceptions. Exemptions to the social housing requirement must be based on strong scientific justification approved by the IACUC or for a specific veterinary medical or behavioral reason. Lack of appropriate caging does not constitute an acceptable justification for exemption.
OLAW concurs with the Guide's statement, “The primary aim of environmental enrichment is to enhance animal well-being by providing animals with sensory and motor stimulation through structures and resources that facilitate the expression of species-typical behaviors and promote psychological well-being through physical exercise, manipulative activities, and cognitive challenges, according to species-specific characteristics.” (See Guide pages 52-54.) An institution's environmental enrichment practices must be species-specific and appropriate for the animals. Devices that animals climb on or through, perch on, or nest in contribute to, rather than detract from, the animal's living space and need not be subtracted from the floor dimensions. Some species are upset by the introduction of novel items. Animals should not be subjected to the presence of items that they find distressing.See also OLAW FAQ F17: May performance standards determine environmental enrichment issues?
OLAW concurs with the Guide that performance standards are to be applied to rodent housing issues. (See Guide pages 56-58.) While the Guide's space recommendations are accepted reference points for addressing space needs, performance standards allow flexibility to improve animal welfare and scientific research. Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC. The IACUC should critically evaluate objective measures of outcome-based performance. The Guide identifies examples of performance indices to assess adequacy of housing including:
Many institutions currently follow procedures and policies in keeping with outcome-based performance indices that meet the standards of the 8th Edition of the Guide. IACUCs may not need to adjust these policies and procedures.
Rodent cages of the size commonly used in the United States may be appropriate for trio breeding. The 8th Edition of the Guide does not add specific, additional engineering standards for breeding configurations. This empowers institutions to determine appropriate housing. The IACUC must consider relevant factors when assessing the adequacy of cage space according to performance standards. Examples of these factors may include:
Blanket, program-wide departures from the Guide for reasons of convenience, cost, or other non-animal welfare considerations are not acceptable. Cages that might be acceptable when litters are born may have insufficient space as pups grow. Whatever parameters are used to establish breeding configurations and weaning procedures, the IACUC must ensure that cage population does not negatively impact animal well-being and overcrowding does not occur.See also OLAW FAQ F10: Can performance standards be used in determining rodent housing practices including management of rodent breeding colonies?
OLAW concurs with the 8th Edition of the Guide. “Rabbits should be housed under conditions that provide sufficient space... to meet physical, physiologic, and behavioral needs. The height of an enclosure can be important to allow for expression of species-specific behaviors and postural adjustments. Cage height should take into account the animals' typical posture and provide adequate clearance for the animal from cage structures, such as feeders and water devices. Space allocations should be assessed, reviewed, and modified as necessary by the IACUC considering the performance indices and special needs determined by the characteristics of the animal.” (See Guide pages 50-52, 56, 59.)
IACUCs may consider the use of a rabbit cage that is 14 inches in height, if appropriate. The IACUC should establish, through performance indices related to animal well-being, that the cage provides sufficient space to meet the physical, physiologic and behavioral needs of the animal. For example, the rabbit must be able to hold its ears in an upright position (if this is natural for the breed) and ears must not be forced to fold over by contact with the cage ceiling. OLAW recognizes the necessity of cost-efficiency and the valid concerns of the community about program cost. Programs should function efficiently, but not at the cost of animal welfare.
OLAW and USDA agree that pharmaceutical-grade1 chemicals and other substances, when available, must be used to avoid toxicity or side effects that may threaten the health and welfare of vertebrate animals and / or interfere with the interpretation of research results2. However, it is frequently necessary to use investigational compounds, veterinarian- or pharmacy-compounded3 drugs, and / or Schedule I4 controlled substances to meet scientific and research goals.
The IACUC is responsible for evaluating the potential adverse consequences of such agents when used for research. In making its evaluation, the IACUC may consider factors including, for example:
The IACUC may use a variety of administrative methods to review and approve the use of such agents. For example, the IACUC may establish acceptable scientific criteria within the institution, rather than on a case-by-case basis. Investigators and IACUCs should consider relevant animal welfare and scientific issues including safety, efficacy, availability of pharmaceutical-grade compounds, and the inadvertent introduction of new variables. Cost saving alone is not an adequate justification for the use of non-pharmaceutical-grade or compounded drugs in animals.
Although the potential animal welfare consequences of complications are less evident in non-survival studies, the scientific issues remain the same. The principles and need for professional judgment outlined above apply to non-survival studies.
Procedures that may cause more than momentary or slight pain or distress to the animals must be performed with sedation, analgesia, or anesthesia agents using veterinary or human pharmaceutical-grade compounds, unless the use of an investigational chemical or formulation is scientifically necessary, appropriately justified, and approved by the IACUC. The use of a non-pharmaceutical-grade euthanasia agent must meet the same standards.
OLAW's guidance on the use of non-pharmaceutical-grade substances was first published in 2003 (Lab Animal. 2003; 32(9):33-36) and posted on the OLAW website on September 11, 2006. The USDA's position on non-pharmaceutical-grade substances may be found in the Animal Care Manual Policy 3. On March 1, 2012, OLAW, with USDA and AAALAC, offered additional guidance through a webinar on the “Use of Non-Pharmaceutical-Grade Chemicals and Other Compounds in Research with Animals”.
See also OLAW FAQ F4: May investigators use non-pharmaceutical-grade compounds in animals?
1 A pharmaceutical-grade compound is a drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA) or for which a chemical purity standard has been established by the United States Pharmacopeia-National Formulary (USP-NF), or British Pharmacopeia (BP).
2 A listing of pharmaceutical-grade drugs and biologics is available through the FDA database. The Orange Book is the reference for FDA-approved human drugs. The Green Book is the reference for FDA-approved veterinary drugs.
3 Veterinary compounding is the customized manipulation of an approved drug by a veterinarian, or by a pharmacist upon the prescription of a veterinarian, to meet the needs of a research study. IACUCs considering the use of veterinary compounding for research purposes are advised to consult Veterinary Compounding for more information about federal regulations.
Ingestion of food and fluid are requirements for proper nutrition. When food or fluid is restricted, the amount of the regulated item earned during testing and the amount of the regulated item freely given should be recorded to ensure each animal receives its minimum daily requirements. (NRC 2003, Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research, Washington: National Academies Press) The IACUC must evaluate the level of restriction and potential adverse consequences in regulating food or fluid. The IACUC must also evaluate the methods for assessing the health and well-being of animals in the animal activities that involve regulation of food or fluid. The IACUC has the authority to approve scientific justifications for departures from the recommendations in the Guide. For instance, using scheduled access to food or fluid sources may be justified by describing procedures based on performance standards that assure adequate maintenance of hydration, body weight, and behavioral and clinical health. It may be necessary to monitor both food and fluid intake if regulation of one influences consumption of the other.See also OLAW FAQ F19: May investigators restrict animals' food and fluid?
Surgical procedures should be defined as major or minor on a case-by-case basis and evaluated by the veterinarian and IACUC to determine their impact on the animal's well-being. (See Guide page 30, 117.) Multiple procedures that may induce substantial post-procedural pain or impairment may be conducted on a single animal only if justified by the PI, and reviewed and approved by the IACUC. Multiple major surgical procedures on a single animal are acceptable only if they are:
Cost saving alone is not an adequate reason for performing multiple major survival surgical procedures. (See Guide page 30.)
Note that under USDA regulations (AWR 2.31 (x) A-C), “No animal will be used in more than one major operative procedure from which it is allowed to recover, unless: (A) Justified for scientific reasons by the principal investigator, in writing; (B) Required as routine veterinary procedure or to protect the health or well-being of the animal as determined by the attending veterinarian; or (C) In other special circumstances as determined by the [Animal Care] Administrator on an individual basis. Written requests and supporting data should be sent to the Animal and Plant Health Inspection Service, Animal Care, 4700 River Road, Unit 84, Riverdale MD 20737-1234”.
OLAW's guidance on use of multiple surgical procedures was first published in 1997 (Contemporary Topics. 1997; 36(2):47-50) and posted on the OLAW website on September 11, 2006.
PHS Policy mandates that Assured institutions use the Guide for the Care and Use of Laboratory Animals as a basis for developing and implementing a program for activities involving animals. (See PHS Policy IV.A.1.) OLAW concurs with the Guide that, “the Guide applies to agricultural animals used in biomedical research, including those maintained in typical farm settings. For animals maintained in a farm setting, the Guide for the Care and Use of Agricultural Animals in Research and Teaching, (FASS 2010) [Federation of Animal Science Societies] is a useful resource. Information about environmental enrichment, transport, and handling may be helpful in both agricultural and biomedical research settings.” (See Guide pages 32-33.)
The USDA position on regulation of agricultural animals may be found in the Animal Care Policy Manual Policy 17.
The 8th Edition of the Guide for the Care and Use of Laboratory Animals was published in January 2011 by the National Research Council of the National Academy of Sciences as the result of a lengthy study by the Institute for Laboratory Animal Research
(ILAR). Since 1985, the PHS Policy has required that all institutions receiving PHS support for animal activities base their programs of animal care and use on the current edition of the Guide. Because the 8th Edition of the Guide contains substantive changes from the previous edition, NIH sought comments to gain insight from institutions that would be affected by the change.
On February 24, 2011, NIH issued a Federal Register Notice (PDF) requesting public comments on (1) NIH's adoption of the 8th Edition of the Guide as a basis for evaluation of institutional programs receiving or proposing to receive PHS support for activities involving animals and (2) NIH's proposed implementation plan (if NIH decides to adopt the 8th Edition of the Guide). The original implementation plan proposed that institutions complete at least one semiannual program and facility evaluation using the 8th Edition of the Guide as the basis for evaluation by March 31, 2012.
A Summary Analysis of the Public Comments on Adoption of the Guide
NIH received a total of 806 comments from Assured institutions, professional organizations, animal advocacy organizations, and individuals. Duplications (7) and comments that were not relevant to issues requested in the Federal Register (2) were removed from the database, leaving 797 comments. Some comments were relevant, but did not address the issues of adoption and implementation of the Guide. These included discussion of rulemaking requirements, comments on the Guide committee selection process, conflicts of interest, requests to extend the public comment period, and requests to remove the character limit on submissions. These comments remain in the database.
600 comments were received from those who identified themselves as individuals. 32 comments identified as official correspondence from Assured institutions were received. (On May 24, 2011, there were 1,030 Assured institutions.) 24 comments were submitted by professional organizations and 4 comments were submitted by animal advocacy organizations. A total of 137 institutions and organizations were represented in the database. A total of 276 comments appear to have originated from form letters authored by 4 organizations or individuals.
Names of individuals were redacted from the comments; organizational affiliation was not redacted. View the public comments on adoption of the Guide.
Adoption and Implementation of the Guide
NIH determined to adopt the 8th Edition of the Guide in December 2011 and released 10 Position Statements to aid Assured institutions in their implementation of the Guide. (See NOT-OD-12-020.) The public was invited to submit comments on their understanding of the Position Statements from December 1, 2011 to February 3, 2012. NIH received a total of 44 comments: 26 responses were from those who identified themselves as individuals, 6 were from PHS Assured institutions, 2 were from animal advocacy organization, and 9 were from professional organizations. The names of individuals or identifiable information were redacted from the comments; organization affiliation was not redacted. View the public comments on understanding of the Position Statements.
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