Animal Use in Research: Federal Agencies Should Assess and Report on Their Efforts to Develop and Promote Alternatives

methods and computer modeling. HHS, USDA, and EPA conduct and fund animal research and regulate products tested on animals. HHS and USDA also oversee federal and nonfederal research facilities including researchers' consideration of alternatives to animal use.

GAO was asked to review issues related to alternatives to animal research. This report (1) describes how HHS, USDA, and EPA ensure researchers consider the use of alternatives to animals and (2) examines the steps the agencies have taken to facilitate the use of alternative research methods and to assess the effect of their efforts on animal use. GAO reviewed documents, such as agency policies and practices relevant to the consideration of alternatives and interviewed agency officials. GAO also interviewed representatives of a nongeneralizable sample of 12 federal and nonfederal research facilities randomly selected across agencies and facilities.

The Department of Health and Human Services (HHS), U.S. Department of Agriculture (USDA), and Environmental Protection Agency (EPA) use a variety of methods to ensure researchers consider alternatives to animal use in research (see figure). Two of these methods are (1) requiring researchers to obtain approval of their research protocols, including their consideration of alternatives, from their institutions, and (2) calling for or recommending researchers to use database searches to identify alternatives. HHS and USDA also help ensure that researchers consider alternatives through the agencies' oversight of research facilities. For example, USDA is to conduct annual inspections of nonfederal research facilities. Futhermore, the agencies have provided training to researchers on the consideration of alternatives.

HHS, USDA, and EPA have facilitated the development and use of alternatives to animal use in research through individual and collaborative efforts. These efforts include agency strategies and policies for promoting the use of alternative methods and the development of testing methods that rely on non-animal models. Additionally, the agencies are members of the Interagency Coordinating Committee on the Validation of Alternative Methods, which is managed by HHS's National Institute of Environmental Health Sciences. The committee promotes testing methods that protect human health and the environment while reducing animal use. The interagency committee's 2018 strategic roadmap calls for it to identify appropriate metrics for monitoring progress and measuring success in adopting alternatives. However, the committee and its member agencies have not routinely developed or reported metrics that demonstrate how their efforts to encourage the use of alternative methods affect animal use. They have also not designated an interagency workgroup to address the challenges related to developing and reporting such metrics. Facilitating the establishment of such a workgroup would help the committee and its member agencies better monitor their progress across the range of their efforts to reduce animal use and report members' progress to the public.

GAO recommends that HHS's National Institute of Environmental Health Sciences facilitate the establishment of an interagency workgroup to develop metrics for assessing progress on the development and promotion of alternatives to animal use and incorporate those metrics into public reports. HHS agreed with our recommendation.

U.S. research facilities use a wide range of animal species in research,  testing, teaching, and experimentation, and some procedures used in  such research produce pain or distress in the animals. These procedures  may include surgery, inhalation toxicity studies, studies involving tumor  growth, and food or water deprivation or restriction. However, a growing  number of alternatives are available that enable researchers to replace,  reduce, or refine their use of animals. Researchers and agencies may  seek to develop and use alternatives for several reasons, including the  desire to promote animal welfare, the potential to provide more accurate  information about human diseases or health than animal research can  provide, and the potential to conduct research at a lower cost and in a  shorter time frame than with research using animals. Alternatives that  may replace animals or reduce their use in research include in vitro  methods (i.e., testing cells and tissues in test tubes or other chambers)  and computer modeling in biomedical research or drug safety testing.  Alternatives that may refine animal use include surgical methods that  minimize or eliminate pain and distress and adjustments that improve  animals’ psychological and behavioral welfare such as enhancements to  housing conditions.

Federal agencies are involved in animal research in several ways.  Agencies such as the National Institutes of Health (NIH) within the  Department of Health and Human Services (HHS) and the Agricultural  Research Service (ARS) within the U.S. Department of Agriculture  (USDA) conduct or fund research using animals to answer important  questions about human or animal health. Other agencies, such as the  Environmental Protection Agency (EPA) and HHS’s Food and Drug  Administration (FDA), regulate products that are tested for safety or  efficacy using animals and conduct research to support regulatory  activities. In addition, USDA’s Animal and Plant Health Inspection Service  (APHIS) and NIH are responsible for overseeing the welfare of certain  species of animals used for certain types of research.

Federal laws, regulations, and policies that govern how animals are to be  used and cared for call for the consideration of alternatives to animal  research. In particular, the Animal Welfare Act, administered by APHIS,  calls for the Secretary of Agriculture to establish standards for animal  care, treatment, and practice that minimize pain and distress of animals in  research facilities and directs that such standards require researchers to  consider alternatives to any procedure likely to produce pain or distress in  an experimental animal. The act’s implementing regulations also require  that research facilities provide annual reports to APHIS containing  assurances that each of their researchers considered alternatives to  painful procedures. Similarly, under the Health Research Extension Act of  1985, applicants for funding from NIH and other HHS agencies covered  by the act must provide certain assurances to NIH for research on  animals. These assurances include that researchers involved with animal  care, treatment, and use have available to them instruction or training in  the concept, availability, and use of research or testing methods that limit  the use of animals or limit animal distress.

Furthermore, in 1985, federal agencies that use or require the use of  experimental animals adopted certain principles that apply when agencies  develop requirements for testing, research, or training procedures  involving the use of vertebrate animals and whenever these agencies  actually perform or sponsor such procedures. Among other things, these  principles call for researchers to use the minimum number of animals  required to obtain valid results and to consider alternative methods such  as mathematical models, computer simulation, and in vitro biological  systems. The principles call for researchers to consider alternatives  regardless of whether the procedures cause pain or distress to the  animals.

Federal agencies also have undertaken various efforts to further develop  and promote alternatives to animal research. For example, in June 2018,  EPA issued a strategic plan for the reduction of testing in vertebrates for  chemicals that the agency regulates under the Toxic Substances Control  Act. In addition, the National Institute of Environmental Health Sciences  within NIH manages the Interagency Coordinating Committee on the  Validation of Alternative Methods (ICCVAM), which is composed of  officials from U.S. federal regulatory and research agencies that require,  use, generate, or disseminate toxicological and safety testing  information. One of the committee’s purposes is to reduce, refine, or  replace the use of animals in testing where feasible.

We have previously reported on the use of animals in federal research. In  May 2018 we issued a report on selected agencies’ reporting and sharing  of information on their animal use programs. You also asked us to review  federal agencies’ efforts related to the use of alternatives to animals in  federal research. This report (1) describes how HHS, USDA, and EPA  ensure that researchers consider the use of alternatives to animals and  (2) examines the three agencies’ efforts to facilitate the use of alternative  research methods and assess the effect of their efforts on animal use.

To conduct our work, we selected agencies and offices within HHS,  USDA, and EPA that conduct or fund research using animals, regulate  products that may be tested using animals, or have an oversight role in  relation to the Animal Welfare Act or Health Research Extension Act.

Based on our review of documents from and interviews with agency  officials, we selected the following agencies and offices that have a role in  animal research and are relevant to our review:

HHS’s Centers for Disease Control and Prevention (CDC), FDA, and

USDA’s ARS, APHIS, and National Institute for Food and Agriculture;

EPA’s Office of Research and Development, Office of Science  Coordination and Policy, and Office of Chemical Safety and Pollution  Prevention. The latter includes the Office of Pesticide Programs and  Office of Pollution Prevention and Toxics.

To describe how EPA, HHS, and USDA ensure researchers consider the  use of alternatives to animals, we reviewed federal statutes, regulations,  policies, principles, and guidance governing animal research funded or  overseen by federal agencies, including:  the Animal Welfare Act and USDA’s regulations and guidance for  implementing the act;  the section of the Health Research Extension Act that pertains to animal  care, NIH’s policy for implementing that section of the act—the Public  Health Service Policy on Humane Care and Use of Laboratory Animals  (Public Health Service Policy)—and related NIH guidance;

U.S. Government Principles for the Utilization and Care of Vertebrate  Animals Used in Testing, Research, and Training, developed by the  Interagency Animal Research Committee; and  the Guide for the Care and Use of Laboratory Animals published by the  National Academies of Sciences, Engineering, and Medicine (National  Academies).

We reviewed documentation from APHIS and NIH on their  implementation of requirements and guidance for researchers to consider  alternatives. In particular, we reviewed APHIS’s inspection guide and  obtained copies of citations agency inspectors issued to research facilities  for noncompliance with the Animal Welfare Act requirement to consider  alternatives. We also reviewed NIH’s template for site visit questions. In  addition, for each of the selected agencies and offices within HHS, USDA,  and EPA, we reviewed documentation on their oversight of research, in  particular researchers’ consideration of alternatives.

We interviewed APHIS and NIH officials directly responsible for  overseeing compliance with the Animal Welfare Act or the Health  Research Extension Act regarding the agencies’ oversight of animal  research. In particular, we discussed researchers’ consideration of  alternatives to animal research and the agencies’ procedures for and  results from conducting inspections or site visits at research facilities in  fiscal years 2015 through 2018.

To learn more about researchers’ consideration of alternatives to animal  research, we reviewed documents from and interviewed members of  animal care and use committees and other representatives from a  nongeneralizable sample of 12 research facilities—six federal facilities  and six nonfederal facilities—that conduct animal research. To select the  six federal facilities, we randomly selected one facility each from APHIS,  ARS, CDC, EPA, FDA, and NIH. We selected these facilities from among  the agency components that agency officials identified as performing the  most animal research. To select the six nonfederal facilities, we obtained  a list of research facilities that were registered with APHIS as of  September 26, 2018. We randomly selected from this list facilities that (1)  had an assurance under the Health Research Extension Act approved by  NIH as of September 26, 2018, and (2) were shown in publicly available  federal databases as having received federal funding from EPA, HHS, or  USDA at some point from 2015 through 2018. We used these criteria to  select facilities that interacted with at least one of the federal agencies in  our scope. We then interviewed the chair and other members of each  facility’s animal care and use committee about the process each  committee uses to determine that researchers adequately consider  alternatives to animal use. We then performed a content analysis of the  officials’ responses to our questions. The views of these representatives  are not generalizable to all research facilities that perform animal  research but provide examples of how federal and nonfederal research  facilities have addressed requirements to consider alternatives. We also  obtained copies of the protocol forms that the 12 facilities require their  researchers to use to describe their planned use of animals and  consideration of alternatives, and we compared the ways in which the  forms require researchers to document how they identified and  considered alternatives.

To examine the efforts of HHS, USDA, and EPA to facilitate the use of  alternative research methods and assess the effect of their efforts on  animal use, we identified and reviewed statutes directing agencies to  develop alternatives to animal research or plans for increasing the use of  alternatives. In addition, we reviewed agency documentation related to  each agency’s efforts to facilitate the use of alternatives, including  strategic plans, regulations and guidance regarding the review of the  safety and efficacy of products, and information published on agency  websites and in agency reports on alternatives the agencies have  developed. We interviewed officials from HHS, USDA, and EPA and their  component agencies and offices to identify illustrative examples of efforts  to develop new alternative methods or promote the use of alternative  methods by others. During our interviews with representatives from the 12  selected research facilities, we asked for their views on agencies’ efforts  to facilitate the use of alternative research methods, challenges the  agencies face in developing or promoting alternatives, and how  researchers at the institutions obtain information on alternatives. To  describe interagency collaboration to facilitate the use of alternative  research methods, we reviewed documents from ICCVAM, such as its  website and 2018 strategic roadmap, and documents on the Toxicology in  the 21st Century Program. We also interviewed agency officials about  their efforts to collaborate with other agencies and nongovernmental  organizations.

For additional context on both objectives, we interviewed officials from  organizations that we identified through our document reviews and  interviews and that represent researchers, advocate for animal welfare or  the use of alternatives to animal research, provide training or guidance on  animal research, or have a role in ensuring the humane treatment of  animals used for research. In addition, we attended meetings related to  animal research or the development of alternatives, including the 2018  national meeting of the American Association for Laboratory Animal  Science, a one-day series of presentations in November 2018 sponsored  by the Center for Alternatives to Animal Testing at the Johns Hopkins  University Bloomberg School of Public Health, and a May 2019 ICCVAM  public forum with presentations by member agencies.

We conducted this performance audit from June 2018 to September 2019  in accordance with generally accepted government auditing standards.  Those standards require that we plan and perform the audit to obtain  sufficient, appropriate evidence to provide a reasonable basis for our  findings and conclusions based on our audit objectives. We believe that  the evidence obtained provides a reasonable basis for our findings and  conclusions based on our audit objectives.

Federal agencies conduct a variety of activities related to animal  research. These activities include:  funding intramural research conducted by agency personnel at federal  facilities;  funding extramural research conducted by universities, industrial firms,  and other nonfederal entities through contracts, grants, or cooperative  agreements; establishing guidelines for regulating products that may have been tested  for safety or efficacy using animals; and overseeing the welfare of animals used for research.

Table 1 shows key activities related to animal research or use that HHS,  USDA and EPA and their component agencies and offices are involved in  through their funding of intramural and extramural research and  regulation of products.

Some agencies within USDA and HHS have roles in overseeing animal  welfare at federal and nonfederal research facilities. Under the Animal  Welfare Act and its implementing regulations, USDA’s APHIS oversees  federal and nonfederal research facilities to ensure the humane treatment  of covered species of warm-blooded animals when they are used in  research, teaching, testing, or experimentation. These species include  dogs, cats, nonhuman primates, guinea pigs, hamsters, rabbits, horses  used for research purposes, and (with certain exceptions) other warm- blooded animals. Requirements under the act related to consideration of  alternatives to animal research include the following:

Under the act, research facilities are to appoint an animal care and use  committee to, at least semiannually, review the facility’s program for  humane care and use of covered animals, inspect all facilities, and  prepare reports of its evaluation. The committee is responsible for  reviewing research proposals to determine whether the proposed  activities are in accordance with the act. This includes a review of  research proposals to determine whether researchers have (1)  considered alternatives to procedures that may cause more than  momentary or slight pain or distress to covered animals and (2) have  provided a written narrative description of the methods and sources they  used to determine that alternatives were not available. The committee  can ask a researcher to explain why any alternatives found are not used  in the researcher’s proposal or withhold approval of the proposal.

Facilities that used or intended to use live covered animals in research  are to submit a retrospective annual report about those animals to APHIS  on or before December 1 of each calendar year. In particular, the annual  reports are to include an assurance that each researcher considered  alternatives to painful procedures.

HHS’s NIH is responsible for establishing guidelines implementing certain  provisions of the Health Research Extension Act of 1985. NIH’s  responsibilities under the act include reviewing federal and nonfederal  research facilities’ vertebrate animal care and use programs to determine  whether they meet relevant standards and are thereby eligible to receive  funding from HHS agencies covered by the act, including NIH. NIH  implements the animal care provisions of the act through its Public Health  Service Policy. The policy’s requirements related to research facilities’  consideration of alternatives include the following:

Consistent with the act, NIH’s Public Health Service Policy directs  facilities to provide for NIH’s approval a document that describes their  vertebrate animal care and use program and that provides assurances  that the research institution meets applicable standards. Such  assurances must include a synopsis of training or instruction in research  or testing methods that minimize the number of vertebrate animals  required to obtain valid results and minimize animal distress and that the  facility offers to scientists, animal technicians, and other personnel  involved in animal care, treatment, or use.

As a condition of receiving funding for animal research from HHS  agencies, facilities must, for the most part, adhere to the eighth edition of  the Guide for the Care and Use of Laboratory Animals (Guide). The  Guide states that in preparing and reviewing research protocols,  researchers and animal care and use committees should consider the  availability or appropriateness of using less invasive procedures, other  species, isolated organ preparation, cell or tissue culture, or computer  simulation. The Guide does not limit this to research that is painful or  distressful.

NIH conducts site visits at selected research facilities to assess  compliance with the act. Whereas the Animal Welfare Act applies to  certain warm-blooded animals, the definition of animals used for the  purposes of the Health Research Extension Act covers all vertebrates,  including the mice, rats, and fish species commonly used in laboratory  research.

Other laws relevant to the consideration of alternatives include the  following:

The National Institutes of Health Revitalization Act of 1993 directs the  Director of NIH to prepare a plan to conduct or support research into  methods of biomedical research and experimentation that do not require  the use of animals, that reduce the number of animals used in such  research, and that produce less pain and distress in such animals. The  act also directs NIH to prepare a plan for establishing the validity and  reliability of the new methods it develops, encouraging the scientific  community’s acceptance of these methods, and training scientists in  using such methods. The act further directs NIH to periodically review  this plan and, as appropriate, make revisions and include those revisions  in a biennial report. In response to the act, in September 1994 NIH  established ICCVAM as an ad hoc committee.

The ICCVAM Authorization Act of 2000 directed NIH to establish the  ICCVAM as a permanent interagency committee under NIH’s National  Toxicology Program Interagency Center for the Evaluation of Alternative  Toxicological Methods. ICCVAM is administered by the National  Institute of Environmental Health Sciences. The act specifies that  ICCVAM be composed of the heads (or their designees) of 15 agencies  or subagencies, including EPA, agencies within HHS, and USDA. The  National Institutes of Standards and Technology joined voluntarily in  2016. The act directed ICCVAM to, among other things, review and  evaluate alternative test methods that may be acceptable for specific  regulatory uses and to prepare biennial progress reports. Under the act,  an alternative test method is one that reduces the number of animals  required; refines procedures to lessen or eliminate pain or distress to  animals or enhances animal well-being; or replaces animals with non- animal systems or one animal species with a species presumed to have  less ability to feel pain, such as replacing a mammal with an invertebrate.  In January 2018, ICCVAM published a strategic roadmap articulating its  vision to meet its purpose.

The Frank R. Lautenberg Chemical Safety for the 21st Century Act  amended the Toxic Substance Control Act in 2016 to include language  on the use of alternative methods. The act directs the Administrator of  EPA to reduce and replace, to the extent practicable, scientifically  justified, and consistent with the policies of the Toxic Substances Control  Act, the use of vertebrate animals in the testing of chemical substances  or mixtures under the Toxic Substances Control Act. The act also directs  the Administrator to develop a strategic plan to promote the development  and implementation of alternative test methods and strategies to reduce,  refine, or replace vertebrate animal testing.

HHS, USDA, and EPA Have Used a Variety of Methods to Ensure Researchers Consider Alternatives to Animals

Methods HHS, USDA, and EPA have used to ensure that researchers  consider alternatives to animal research include requiring researchers to  describe and document their consideration of alternatives. In addition,  USDA’s APIHS and HHS’s NIH help ensure that researchers consider  alternatives by overseeing research facilities and these facilities’ animal  care and use committees, including the committees’ review of animal  research protocols. USDA and NIH also provide training to researchers  and animal care and use committees to help ensure researchers have  considered alternatives.

HHS, USDA, and EPA Call for Written Descriptions of the Consideration of Alternatives and Recommend a Method for Identifying Alternatives

For research that they conduct or fund, component agencies and offices  within HHS, USDA, and EPA call for individual researchers to describe  their consideration of alternatives to animal research. USDA’s APHIS and  HHS’s NIH require research facilities to consider alternatives through the  agencies’ implementation of the Animal Welfare Act regulations and  Public Health Service Policy, respectively. EPA research is covered by  the two laws to the extent that it uses animals covered by the Animal  Welfare Act or Health Research Extension Act. Table 3 summarizes the  factors that determine whether researchers are required under the acts to  consider alternatives.

The steps HHS, USDA, and EPA take to help ensure that agency  researchers and the researchers that they fund or oversee meet the  requirement to consider alternatives include (1) calling for written  descriptions of researchers’ consideration of alternatives and (2)  prescribing or recommending that researchers use searches, such as of  databases of published scientific literature, to identify alternatives.

Call for written descriptions. As specified in the Animal Welfare Act  regulations and Public Health Service Policy, HHS, USDA, and EPA call  for researchers to send written descriptions of research projects involving  animals to animal care and use committees for their review and approval.  In particular, the Animal Welfare Act regulations require these  committees to determine that researchers have provided a written  narrative description of the methods and sources they used to determine  that alternatives were not available. The Public Health Service Policy  requires that researchers’ institutions submit written descriptions of  research projects to the committees and for the committees to determine  that researchers’ procedures avoid or minimize discomfort, distress, and  pain to animals, consistent with sound research design, among other  things, and that researchers follow the U.S. Government Principles for  the Utilization and Care of Vertebrate Animals Used in Testing,  Research, and Training. The principles require the consideration of  alternatives. In our review of protocol forms from our sample of 12  research facilities (including HHS, USDA, and EPA facilities), we found  that all of the forms requested information on researchers’ consideration  of alternatives, though the forms varied in the particular information they  requested. The types of information requested included a rationale for  involving animals and for the number of animals to be used, assurance  that research activities do not unnecessarily duplicate previous  experiments, and a description of the methods and sources used to  determine that alternatives were not available. Several of the protocol  forms required researchers to identify alternatives considered but not  adopted.

Recommended method for identifying alternatives. In their  implementation of the Animal Welfare Act and Health Research  Extension Act, respectively, USDA and NIH consider database searches  as a best practice for researchers using animals covered by the acts to  identify and consider alternatives to animal testing. A database search  involves a researcher using keywords related to the planned use of  animals to query citations in databases of published scientific literature.  From April 1997 through July 2018, USDA maintained a policy, known as  Animal Care Policy #12, in its animal care policy manual. In Policy #12,  the agency recommended a database search as the most effective and  efficient method for demonstrating compliance with the requirement to  consider alternatives to painful or distressful procedures. According to  USDA’s Deputy Administrator responsible for implementation of the  Animal Welfare Act regulations, in July 2018, USDA placed the policy in  inoperative status after determining that some research facilities and  agency inspectors had misinterpreted the policy as a requirement.  Moreover, in response to the 21st Century Cures Act, USDA is reviewing  its animal care policy manual, including Policy #12, to ensure the policies  in the manual conform with the Animal Welfare Act and its implementing  regulations, harmonize with NIH guidance, and reduce researcher burden  where possible.

According to the Deputy Administrator, as of June 2019, USDA had not  decided what, if anything, it would do to revise or replace Policy #12.  According to a draft interagency report in response to the 21st Century  Cures Act, USDA will make any revised and future policies involving the  use of animals available for public comment using regulations.gov or a  similar service. However, according to the Deputy Administrator, even  though Policy #12 is inoperative, USDA continues to advocate for  database searches, particularly through the USDA Animal Welfare  Information Center’s provision of information to the scientific community  about how to search for alternatives. According to a senior NIH official,  NIH requires that agency researchers conduct database searches. Also,  in a sample animal study proposal form NIH has provided to animal care  and use committees, NIH recommends that researchers at other facilities  conduct database searches. Furthermore, 11 of the 12 research facilities  we reviewed (including HHS, USDA, and EPA facilities) used research  protocol forms that required or recommended that their researchers  conduct a database search for alternatives to animal research.

Agencies may apply additional requirements to individual researchers at  their own facilities or through grants they fund, in addition to applying the  requirements of the Animal Welfare Act and Health Research Extension  Act. For example, CDC’s Fort Collins, Colorado, facility requires  researchers to provide assurance on their protocol forms that the facility’s  animal care and use committee’s statistician reviewed the form to  determine whether the research would use an appropriate number of  animals or explain why a review of the number of animals did not occur.  Similarly, the Chairman of APHIS’s National Wildlife Research Center  committee told us that its animal care and use committee includes a  biostatistician who conducts an analysis to ensure that the numbers of  animals to be used will produce statistically significant results. USDA’s  National Institute for Food and Agriculture requires applicants for funding  from the agency’s Agriculture and Food Research Initiative Competitive  Grants Program to use statistical power analysis, when appropriate, to  determine the sample sizes of animals to be used in research. USDA  officials told us that this type of analysis provides a justification for the  number of animals needed to provide valid results and helps prevent the  unnecessary use of animals.

Agencies may also require information on animal use in proposals  submitted by extramural researchers. For example, NIH instructs  researchers to describe the use of animals in their work in a section of  grant applications, contract proposals, and cooperative agreements.  Specifically, when submitting a proposal, researchers must justify to  agency officials and other reviewers that the species used is appropriate  for the proposed research and explain why research goals cannot be  accomplished using an alternative model, such as computational, human,  invertebrate, or in vitro models.

APHIS and NIH Oversee the Review and Approval of Animal Research Protocols by Animal Care and Use Committees

APHIS and NIH help ensure that researchers consider alternatives  through the agencies’ oversight of research facilities and these facilities’  animal care and use committees, including the committees’ review of  animal research protocols. In particular, APHIS collects and reviews  annual reports from federal and nonfederal research facilities in which the  facilities are required to provide an assurance that researchers  considered alternatives. The Animal Welfare Act requires APHIS to  annually inspect nonfederal research facilities to determine whether the  facilities are in compliance with the act. As part of a facility inspection,  APHIS inspectors are to examine whether researchers have met the  requirement to consider alternatives to any procedure likely to produce  pain in or distress to species of animals covered by the act.

According to APHIS officials, inspectors examine a sample of approved  animal research protocols to check whether the protocol forms include a  written narrative on the consideration of alternatives and to ensure that  the facility’s animal care and use committee approved the protocol forms.  The inspectors may issue citations of noncompliance if they find  inadequate documentation that researchers associated with one or more  protocols considered alternatives to procedures that may cause more  than momentary or slight pain or distress to animals. APHIS provided us  with inspection reports for fiscal years 2015 through 2018 in which  inspectors issued 57 citations to research facilities for noncompliance with  the Animal Welfare Act regulations that require researchers to consider  alternatives to animals or issued “teachable moments.” The inspection  reports included some citations that, according to APHIS officials, were  incorrectly issued because inspectors interpreted the Policy #12  recommendations on database searches as requirements.

In addition, NIH’s Office of Laboratory Animal Welfare is responsible for  the general administration and coordination of the Public Health Service  Policy and provides specific guidance, instruction, and materials to  research facilities that receive funding from agencies covered by the act.  For all such facilities, NIH is to review the facilities’ assurance documents  describing their animal care and use programs. In particular, the Animal  Welfare Assurance document is to describe the procedures—including  review of animal research protocols—that the animal care and use  committees follow to fulfill the directives of the NIH Public Health Service  Policy. Further, NIH conducts site visits at a small number of facilities.  The Public Health Service Policy states that each awardee institution is  subject to review at any time by agency staff and advisors to assess the  adequacy and accuracy of the institution’s compliance or expressed  compliance with the policy, and this review may include a site visit.  According to NIH officials, when agency staff conduct site visits, they  examine the facility’s protocol form to confirm that its animal care and use  committee requests information from researchers about their  consideration of alternatives. NIH officials may also examine a sample of  approved protocol forms during a site visit. According to NIH officials, the  Office of Laboratory Animal Welfare conducted 38 site visits in fiscal  years 2015 through 2018 and found one deficiency related to the  consideration of alternatives.

USDA and NIH Provide Training to Researchers and Facilities’ Animal Care and Use Committees to Help Ensure Alternatives Are Considered

USDA and NIH have provided training to researchers and animal care  and use committee members on the requirements of the Animal Welfare  Act and the Health Research Extension Act. The training has addressed,  among other things, the requirement to consider alternatives and has  included advice on how to search for alternatives.

Through its Animal Welfare Information Center, USDA provides training  on how to conduct database searches for alternatives to animal research  and assists individual researchers with their literature searches.  According to USDA staff, the information center provides three workshops  per year on meeting the requirements of the Animal Welfare Act, each  lasting a day and a half. The workshops are open to anyone working with  animals in research, including scientists, veterinarians, librarians, and  animal care and use committee members. The center also gives  workshops upon request at specific facilities. Additionally, the center’s  website contains resources for conducting literature searches, and,  according to a senior information center official, the center plans to put  workshops into an online format that will be available upon demand.  According to the official, the center conducted 137 database searches  upon request in fiscal years 2014 through 2018.

NIH has also provided training on the consideration of alternatives to help  researchers meet their requirements under the Health Research  Extension Act. For example, in 2014 NIH presented a webinar on  searches for alternatives. The webinar, titled Meeting Requirements for  Alternatives Searches and available on NIH’s website, provides advice on  how to conduct database searches. For example, the webinar provided  advice on the timing of the search, the search strategy, and particular  databases to use. In September 2015, NIH presented a webinar  demonstrating how to use NIH’s database of research projects to find  researchers, projects, and publications that may help replace, reduce,  and refine the use of animals in research.

The NIH Office of Laboratory Animal Welfare provides on its website a  sample animal study protocol form that emphasizes database searches  for any procedures that cause more than momentary or slight pain or  distress to the animals. In addition, according to a senior official from the  NIH office overseeing the agencies’ intramural research using animals,  researchers at NIH must complete an online course regarding animal use  every 3 years. The course includes a section on replacing, reducing, and  refining animal use and outlines how researchers are to report literature  searches in order to show they considered alternatives.

HHS, USDA, and EPA Have Facilitated the Development and Use of Alternatives to Animals in Research but Have Not Consistently Assessed the Effect of Their Efforts

EPA, HHS, and USDA have facilitated the development, use, and  promotion of alternative research methods through individual and  collaborative efforts, including strategies for promoting the use of  alternative methods and development of policies and guidance on  alternative methods. The three agencies have also developed alternative  research methods that rely on non-animal models and procedures to test  how various products would affect humans. Additionally, the agencies  have worked collaboratively with each other and with nonfederal  stakeholders to promote alternative methods, in particular through  ICCVAM, which is required to report to the public on its progress.  However, ICCVAM and its member agencies have not routinely  developed or reported metrics for assessing the effect that their efforts  are having on animal use.

EPA and Agencies within HHS and USDA Have Issued Strategies, Policies, and Guidance on Alternative Research Methods

EPA has issued a strategic plan and FDA has issued a roadmap for the  use of methods that may reduce animal use in assessments of the safety  and efficacy of various products. Both agencies and others within HHS  and USDA have also issued guidance on using alternatives to animal  research in particular contexts, such as vaccine testing.

Strategic Plan and Guidance for Reducing Animal Testing for EPA-Regulated Toxic Chemicals and Pesticides

In June 2018, EPA’s Office of Chemical Safety and Pollution Prevention  issued a strategic plan for the reduction of vertebrate animal testing for  toxic chemicals regulated under the Toxic Substances Control Act. The  office developed and issued this strategic plan to implement a provision in  the Frank R. Lautenberg Chemical Safety for the 21st Century Act  (Lautenberg Act) calling for such a plan. The strategic plan describes a  multi-year process with incremental steps for adopting and integrating  methods that do not use vertebrate animals in evaluating chemicals  regulated by the Toxic Substances Control Act for their effect on human  health and the environment. The strategic plan states that the agency’s  long-term goal is to reduce and eventually eliminate vertebrate animal  testing for chemicals regulated under the act. Pursuant to the strategic  plan, in June 2018 EPA published a list of methods the agency had  identified that require no vertebrate testing and that are capable of  providing information of equivalent or better scientific reliability and quality  than that which would be obtained from vertebrate animal testing.  According to EPA, the agency plans to update the list at least once a  year. EPA’s strategic plan calls for other near-term activities such as  retrospectively identifying and evaluating the studies that it has requested  and received for both new and existing chemicals. The plan states that  EPA will complete this analysis in 2019 and use the results to support the  future development of alternative methods to fit the agency’s needs.

In May 2011, EPA’s Office of Chemical Safety and Pollution Prevention  issued a strategic plan in response to a 2007 National Academies report  calling for a more efficient and informative risk assessment process to  predict and characterize potential human health and environmental  hazards from exposures to pesticides. The office’s strategic plan  envisions using a combination of computational and predictive modeling  approaches, in vitro techniques, and targeted in vivo testing to  supplement or replace the existing toxicity tests required in federal  regulations for pesticide registration under the Federal Insecticide,  Fungicide, and Rodenticide Act.

Pursuant to this strategic plan, EPA’s Office of Chemical Safety and  Pollution Prevention has issued guidance on data requirements for  assessing pesticide safety that may reduce animal use. For example,  EPA issued guidance in May 2013 on the data that the agency needs in  order to adequately assess pesticide risks. The guidance also provided  information to manufacturers on how to request waivers from the data  requirements, which would enable the manufacturers to reduce animal  use. EPA also issued guidance in November 2016 that allows pesticide  manufacturers to request a waiver from the requirement to provide data  on acute toxicity tests and that contains a policy statement waiving all  acute lethality dermal studies for formulated pesticide products; such  waivers can reduce the need for pesticide manufacturers to conduct tests  using animals. For example, EPA reported granting a total of 223  waivers in fiscal years 2016 and 2017, pursuant to the agency’s May  2013 guidance for toxicity studies, which the agency estimated avoided  the use of 85,000 animals and saved pesticide manufacturers $26.4  million in conducting toxicity studies.

In February 2016, EPA announced an effort to evaluate and implement  alternative methods for tests involving acute oral, dermal, and inhalation  toxicity; skin and eye irritation; and skin sensitization. As part of this  effort, in April 2018, EPA issued a draft policy to reduce the use of  animals in testing chemicals to evaluate whether they cause an allergic  reaction, inflammation, or sensitization of the skin. EPA’s policy describes  conditions under which the Office of Chemical Safety and Pollution  Prevention will accept alternative approaches to laboratory animal studies  for identifying skin sensitization hazards.

Roadmap for Developing and Evaluating Tools for Assessing FDA-Regulated Products and Guidance for Industry

In December 2017, in response to direction from the FDA Commissioner,  FDA developed a roadmap to foster the development and evaluation of  emerging tools and methods that can improve toxicology methods for  assessing the safety of FDA-regulated products. The roadmap does not  have an explicit goal to replace, reduce, or refine animal testing but states  that new methods may have the potential to do so. In that regard, the  roadmap states that FDA will encourage medical product sponsors to  submit a scientifically valid approach for using a new method early in the  regulatory process and to engage in frequent communication with the  agency about the suitability of that method. In addition, the roadmap  recommended that FDA establish an organizing committee; conduct  training; foster communication and collaboration with stakeholders, such  as industry and academia; engage in research; and track and report  annually on its progress. In June 2019, FDA posted its first annual report  on its progress in implementing the roadmap.

Previously, FDA had taken steps to reduce animal use by issuing  guidance to members of industry seeking approval for FDA-regulated  products. In general, FDA guidance states that industry may choose to  use an approach—such as a non-animal testing method—other than one  set forth in guidance as long as it complies with relevant statutes and  regulations. FDA has also taken more specific steps to modify guidance  to promote the use of alternative methods. For example, in 2012, FDA  issued guidance to industry that states that firms may use non-animal  alternative methods to test the toxicological safety of pharmaceutical  drugs if the methods are appropriate or scientifically justified. In 2013,  FDA issued guidance that, among other things, allowed industry to use in  vitro assays rather than mice to detect toxins in shellfish meant for  human consumption; this guidance subsequently played a role in the  adoption of additional methods that do not employ animal use.

Other HHS and USDA Agencies’ Guidance on the Use of Alternatives to Animal Research

Other HHS and USDA agencies within our scope do not have strategic  plans or roadmaps that promote a comprehensive strategy for alternative  research methods, but some of the agencies have issued guidance to  their own researchers or to regulated entities that may reduce animal use.  For example, in 2017, APHIS updated its guidance to allow  manufacturers of animal vaccines, inactivated bacterial products, and  antibody products to request an exemption to animal safety testing if the  products have a documented history of acceptable safety results and  controlled manufacturing processes that ensure batch consistency and  sterility. APHIS also issued a notice in 2017 of a testing option that can  reduce by up to 50 percent the number of hamsters required for potency  testing of vaccines for the bacterial disease leptospirosis, according to the  notice. In addition, APHIS issued memorandums in 2013 and 2015 that  provide guidance on in vitro techniques that researchers may use instead  of animals to test the potency of vaccines.

Some agencies have also adopted alternative methods for their  researchers without issuing specific guidance to do so. For example, in  September 2018, CDC began routine use of an in vitro procedure  developed by the agency that allows its laboratories to test for botulism in human serum specimens without using mice. CDC officials stated that  this method is fast and inexpensive and would reduce the need for  hundreds of mice. CDC officials told us that their researchers plan to  expand use of the in vitro procedure to test other types of specimens,  further reducing the use of animals.

HHS, USDA and EPA Have Developed Alternative Research Methods

HHS, USDA, and EPA have made multiple efforts to develop alternative  research methods that, according to the agencies, have reduced animal  use or have the potential to do so. Some of these efforts target reducing  the use of animals in a particular research context while others have  broader applications in toxicology and computer modeling. In some  cases, agency officials provided estimates of how their targeted efforts  have reduced or may reduce animal use. Examples of targeted efforts  include the following:

CDC researchers told us they have evaluated a method that reduces the  number of animals and time needed to produce kits that are distributed  worldwide to identify influenza virus subtypes and thereby aid in strain  selection for the influenza vaccine each season. Under the original  method, antibodies for the kits were generated from blood samples in  sheep that were later euthanized. The CDC researchers concluded that  an alternative automated method that draws antibody-rich plasma from  goats instead of blood from sheep could reduce the time needed to  produce the kits and require fewer animals.

According to FDA officials, FDA is collaborating with others on the  development of an in vitro assay that will be used to test the potency of  human rabies vaccines that manufacturers submit to FDA for approval.  This new method will replace the animal-based assay that is part of the  current license to manufacture rabies vaccine. The officials said that the  animal-based assay uses 600 mice, on average, for each batch of  vaccine submitted by a manufacturer.

According to an ARS research paper, ARS worked with academic  researchers to develop an in vitro method for feeding blood to ticks.  According to ARS officials, the method allows researchers to reduce the  number of animals used when studying disease transmission in animals  via tick-borne pathogens.

APHIS currently holds federal pesticide registrations with EPA for active  ingredients formulated into end-use products, such as rodenticides, that  APHIS uses to prevent damage to agriculture, endangered species, or  critical habitats. According to APHIS officials, the agency uses an EPA- approved method for testing the risks to human health from new pesticide  products that substantially reduces animal use. The method generally  involves progressively increasing the pesticide dose on a relatively small  number of animals compared to the previous method and waiting to  observe whether the dose causes mortality before deciding whether to  increase the dose in further testing. APHIS officials said the new method  reduces animal use by 50 percent or more per test.

EPA’s Endocrine Disruptor Screening  Program Uses Alternatives to Animals  Led by its Office of Science Coordination and  Policy, EPA established the Endocrine  Disruptor Screening Program in 1998 to fulfill  a congressional mandate in the 1996 Food  Quality Protection Act to develop a program  to screen for certain chemicals (e.g.,  pesticides) that affect human hormones. EPA  expanded the scope of the program to  include screening the effects of chemicals on  the human thyroid system and wildlife. The  program began using automated, large-scale  screening methods and computational  models to evaluate and screen chemicals  and, according to EPA, allows EPA to screen  more chemicals in less time, use fewer  animals, and reduce cost.

Agencies’ broader efforts include the integration of advances in biology,  chemistry, and computer science into areas of research, such as  toxicology, that currently rely heavily on animal use. For example, EPA  launched the Toxicity Forecaster in 2007 as an effort to use automated  technologies to expose living cells or isolated proteins to chemicals and  screen the cells or proteins when exposed to chemicals for changes in  biological activity that suggest potential toxic effects. According to EPA  documents, these methods could limit the number of required laboratory  animal-based toxicity tests while quickly and efficiently screening large  numbers of chemicals. According to EPA documents, in the first phase  of this effort, which the agency completed in 2009, EPA evaluated more  than 300 well-studied chemicals (primarily pesticides) that had extensive  data from traditional animal-based toxicity testing; the agency then  compared results from automated screening technologies with the results  from the traditional animal tests. As of 2018, EPA had developed and  made publicly available a library of toxicity data on more than 4,500  chemicals. The availability of the Toxicity Forecaster data has enabled  EPA to reduce the need for animal testing in its Endocrine Disruptor  Screening Program for identifying chemicals that may affect human  hormone systems (see sidebar).

Similarly, FDA has initiated a broad effort to incorporate greater use of  computer modeling and simulation into its decision-making on FDA- regulated products. For example, FDA formed an agency working group  on modeling and simulation in 2017. According to the Chair of the working  group, it does not have an explicit objective to reduce animal testing, but  such reduction is a potential benefit of the testing approaches the group is  advancing. For example, the Chair said that modeling and simulation can  help refine questions about products submitted for FDA approval and  therefore could reduce the number of animal studies needed before  clinical trials.

EPA and NIH have provided funding to extramural researchers to develop  alternative research methods. For example, from 2013 through 2018,  EPA provided $24 million in funding for research on 3-D models  containing human cells (these devices are also known as tissue chips)  that can be used for tests that otherwise might be conducted using  animals. In 2018, EPA also announced $4.25 million in funding for  research to promote the development and use of alternative methods that  reduce, refine, or replace vertebrate animal use for toxicity testing.  Similarly, in 2017, NIH awarded a $962,000 grant to a research facility to  conduct studies of an in vitro human bronchial tissue model for predicting  the toxicity of inhaled chemicals. Additionally, while USDA’s National  Institute for Food and Agriculture did not set aside a specific amount of  funding, in May 2019 the agency made clear to applicants for its Welfare  and Well-being of Agricultural Animals grant program that proposals that  study ways to reduce the need for animals in research are eligible for  funding in fiscal years 2019 and 2020.

HHS, USDA, and EPA Have Collaborated with Each Other and with Other Federal and Nonfederal Stakeholders to Promote Alternative Methods

HHS, USDA, and EPA have joined partnerships to develop, use, and  promote alternative testing methods. For example, the agencies  participate in ICCVAM, which states that its mission is to facilitate the  development, validation, and regulatory acceptance of test methods that  replace, reduce, or refine the use of animals. ICCVAM itself does not  conduct research or validation studies on alternative methods. Instead, it  relies on stakeholders including federal agencies that generate, require,  or use toxicological data; companies that develop toxicological tests; and  animal welfare organizations. According to committee guidelines,  stakeholders can submit the results of their research to ICCVAM, and the  committee then conducts evaluations and makes recommendations on  submissions for regulatory uses that align with the needs and priorities of  member agencies.

Zebrafish Are Used as Alternatives to  Other Animals in Research  A zebrafish is a freshwater, tropical  vertebrate fish that is widely used in  pharmaceutical development and medical  and scientific research due to certain qualities  of its morphology and development as well as  its inexpensive cost to use and maintain.  Some of these qualities include genetic and  structural similarities to other vertebrates that  mimic human responses to certain genes  involved in human diseases and its  transparent embryonic development that  enables researchers to use it as an  alternative model for toxicity screening of  drugs and chemicals. These qualities have  led to the use of zebrafish embryonic models  for automated, large-scale screening  programs by the National Toxicology  Program and the Environmental Protection  Agency, among others.

ICCVAM’s website contains information on current ICCVAM- recommended protocols for specific test methods, such as methods to  test for eye corrosion and irritation and skin sensitization, and on events  organized by NIH and others that are relevant to the replacement,  reduction, or refinement of animal use in research. For example, the  website has a link to a page on NIH’s website that has the slide  presentations given at six webinars from 2017 through 2018 on the use of  zebrafish in toxicology testing. Researchers may use zebrafish and their  embryos in particular as a replacement for other animals, such as mice  (see sidebar).

ICCVAM maintains on its website a list of 108 alternative methods that,  as of June 2019, had been accepted by one or more federal agencies.  These include methods that ICCVAM and its member agencies  contributed to developing or validating. However, according to  ICCVAM’s strategic roadmap issued in January 2018, the committee  concluded that its evaluations of new methods during its first 15 years  were lengthy, inefficient, and resource intensive. ICCVAM concluded that  researchers and test method developers often initiated the development  of alternative methods with little input from federal agencies or regulated  industries and, therefore, these methods did not always meet the needs  of federal agencies. Consequently, these methods were either not  accepted by federal agencies or were accepted by the agencies but not  used by the regulated community. Recognizing these limitations, ICCVAM  initiated a strategic shift in 2013 aimed at adjusting the validation of new  test methods to be more responsive to the needs of federal agencies and  other stakeholders. Accordingly, ICCVAM’s 2018 strategic roadmap set  new objectives for reducing animal use, including the following:

Connect the developers of alternative methods with the regulatory  agencies and the regulated industries that would ultimately use the new  technologies to increase the likelihood of the methods being successfully  developed and implemented.

Foster the use of efficient and flexible practices, such as public-private  partnerships to promote communication and cooperation, to establish  confidence in new methods.

Encourage the adoption and use of new methods and approaches by  federal agencies and regulated industries, such as through training  programs on the use of new methods.

ICCVAM has established workgroups to develop detailed implementation  plans to address roadmap goals. According to the strategic roadmap, the  implementation plans will include four key elements: (1) definition of  testing needs; (2) identification of any available alternative tests and  computer models; (3) a plan to develop integrated approaches to testing  and assessment and defined approaches for interpreting data; and (4) a  plan to address both scientific and nonscientific challenges, including  regulatory challenges, such as international harmonization. As of June  2019, workgroups on acute systemic toxicity, eye and skin irritation, and  skin sensitization had posted information concerning these elements on  ICCVAM’s website. For example, each workgroup authored an article  published in a peer-reviewed journal and posted on the ICCVAM website  about the testing needs of regulatory agencies and information about  available alternatives.

Another interagency effort that has a goal of promoting the use of  alternative methods is the Toxicology in the 21st Century (Tox21)  Program. Formed in 2008, the program is a collaborative effort among  NIH, FDA, and EPA to characterize the potential toxicity of chemicals by  using cells and isolated molecular targets instead of laboratory animals. A  central component of the program is its focus on developing and  evaluating automated in vitro screening methods to assess the hazards of  chemical substances. As of February 2018, the program had used this  method to assess approximately 10,000 chemicals for their potential  impacts on biological systems. According to NIH’s Tox21 website, these  automated methods have yielded high-quality toxicity data on  environmental substances in a fraction of the time that would have been  required with traditional animal testing. To address key challenges in  toxicology testing, the program’s federal partners developed a strategic  and operational plan in March 2018 that expanded the focus of Tox21’s  research activities to include developing alternative test systems that  predict chemical toxicity in humans and addressing the technical  limitations of and strengthening scientific confidence in current in vitro test  systems. According to NIH, activities under the plan will lead to better  predicting chemical toxicity to humans through using non-animal  alternatives such as stem cells and computational models.

Since 2011, federal agencies have also collaborated to develop devices  containing human cells that can be used for tests that otherwise might be  conducted using animals. See figure 1 for an example of such devices,  known as tissue chips or human microphysiological systems. According  to NIH officials, this evolving technology may reduce animal testing and  produce results more relevant to human health. The interagency effort  was initiated in September 2011 when the President announced the  formation of a collaborative project between NIH, the Defense Advanced  Research Projects Agency, and FDA to develop tissue chips loaded with  living human cells to screen the efficacy, safety, and toxicity of drugs,  vaccines, or biological products for humans. Subsequently, in July 2012,  NIH launched the Tissue Chip for Drug Screening program, which  provided 19 grants to research facilities to develop tissue chips that  accurately model the structure and function of the human lung, liver,  heart, and more. In September 2014, NIH announced a second phase of  the program in which researchers would refine existing tissue chips and  combine them into an integrated system that can mimic the complex  functions of the human body. In one example of this collaboration, two  project teams funded by the Defense Advanced Research Projects  Agency—the Massachusetts Institute of Technology and the Wyss  Institute at Harvard University—are working with NIH-funded researchers  to develop platforms that integrate 10 tissue chips that each represent a  separate human organ.

Federal agencies have also collaborated with nongovernmental  organizations on training to promote the use of alternative methods. For  example, NIH and the People for the Ethical Treatment of Animals  (PETA) International Science Consortium offered a webinar series from  March through September 2016 on alternative approaches for assessing  acute inhalation toxicity. Webinar presenters described alternative  approaches for identifying substances likely to cause acute systemic  toxicity through inhalation. Similarly, EPA collaborated with the PETA  International Science Consortium and the Physicians Committee for  Responsible Medicine on webinars in November 2018, February 2019,  and April 2019 that addressed alternative methods for testing the effect of  chemicals on skin, for predicting the effect of inhaled substances, and for  identifying substances that cause irritation or inflammation in human  respiratory systems.

ICCVAM and Its Member Agencies Have Not Established a Workgroup to Develop Metrics on the Effect of Their Efforts on Animal Use

ICCVAM’s strategic roadmap calls for its members to identify appropriate  metrics for prioritizing activities, monitoring progress, and measuring  success toward the goals described in the roadmap. However, ICCVAM  and its member agencies have not routinely developed metrics that they  could report to the public to demonstrate how their individual or collective  efforts to encourage the use of alternative methods have affected or will  affect animal use.

HHS, USDA, and EPA officials, as well as ICCVAM’s roadmap, have  cited challenges to measuring the results of ICCVAM and its member  agencies’ efforts. For example, according to agency officials, differences  in the regulatory contexts in which agencies use data generated through  animal research—for example, in regulation of pesticides versus human  or animal drugs—limit agencies’ ability to develop metrics that can be  applied across multiple agencies. Furthermore, the ICCVAM roadmap  states that measuring the actual impact of encouraging the adoption and  use of new methods is difficult in the United States due to the limited  ability to quantify animals used for toxicity testing. In particular, the Animal  Welfare Act does not cover several species commonly used in research,  including mice, rats, and birds bred for research and cold-blooded  species such as fish. Therefore, research facilities are not required under  the act to report their use of those species to APHIS, and the data APHIS  receives from research facilities can only be used to track a subset of the  total number of animals used for research in the United States.

Although ICCVAM and its member agencies face challenges in  developing metrics, the roadmap also states that agency-specific  mechanisms to measure progress may exist, such as tracking the number  of waivers granted for a particular animal test. For example, as discussed  above, EPA has estimated the extent to which its granting of data waivers  to pesticide manufacturers has reduced animal use and research costs.  Additionally, some agencies have estimated the effect that a new  alternative method could have on animal use. Moreover, officials from  FDA and EPA said that their agencies are able to accept non-animal test  data in lieu of animal test data if the data meet their regulatory needs.  Measuring the frequency with which the agencies receive non-animal test  data instead of animal data could be another mechanism for estimating  changes in animal use.

In addition, the ICCVAM Authorization Act of 2000 requires ICCVAM to  prepare biennial public reports on its progress under the act—including its  efforts to ensure that new and revised test methods are validated to meet  the needs of federal agencies and to reduce, refine, or replace the use of  animals in testing, among other things. ICCVAM, with support from NIH’s  National Institute of Environmental Health Sciences, has issued the  required biennial progress reports since 2001, including the most recent  report issued in July 2018 that covers 2016 and 2017. However, the  committee’s biennial progress reports, including the July 2018 report,  provide few quantitative or qualitative assessments of the progress the  member agencies have made, individually or collectively, toward  reducing, refining, or replacing animal use in testing.

ICCVAM’s strategic roadmap states that it envisions that workgroups will  play a key role in implementing the goals of the strategic roadmap, but  ICCVAM has not designated a workgroup to address the challenges  related to metrics, similar to other workgroups that the committee has  established to address the roadmap’s goals. According to officials from  NIH’s National Institute of Environmental Health Sciences, which  manages the committee, the strategic roadmap is a work in progress and  developing metrics is the third of three roadmap goals. The ICCVAM  Authorization Act of 2000 does not provide the National Institute of  Environmental Health Sciences with authority to direct agencies to  develop and report metrics. However, agency officials agreed that  ICCVAM could facilitate the establishment or designation of a workgroup  of member agencies to identify a range of potential quantitative and  qualitative metrics that member agencies could use to assess their  progress toward reducing, refining, or replacing animal use. By  establishing or designating such a workgroup to develop metrics that the  agencies could use to assess their individual or collective progress  toward reducing, refining, or replacing animal use in testing and by  incorporating those metrics in ICCVAM’s biennial progress reports,  ICCVAM and its member agencies could better monitor progress across  the range of the committee’s efforts and report the members’ progress to  the public.

HHS, USDA, and EPA use a variety of methods to ensure that  researchers—whether employed by or receiving research funding from  these agencies—consider alternative methods to animal research. The  agencies also have engaged in multiple efforts to expand the range of  available alternatives. Under one of these efforts, ICCVAM’s strategic  roadmap calls for its members to identify appropriate metrics for  prioritizing activities, monitoring progress, and measuring success. The  roadmap envisions that workgroups will play a key role in implementing  the goals of the strategic roadmap. However, ICCVAM has not  designated a workgroup to address the challenges related to developing  and reporting metrics. In addition, ICCVAM has issued the required  biennial progress reports since 2001, but the reports provide few  quantitative or qualitative assessments of the progress member agencies  have made, individually or collectively, toward reducing, refining, or  replacing animal use in testing. By establishing or designating a  workgroup to develop metrics to assess the progress member agencies  have made, individually or collectively, toward reducing, refining, or  replacing animal use in testing and by incorporating those metrics in  ICCVAM’s biennial progress reports, ICCVAM and its member agencies  could better monitor progress across the range of the committee’s efforts  and report the members’ progress to the public.

The Director of the NIH’s National Institute of Environmental Health  Sciences should (1) facilitate the establishment or designation of a  workgroup of representatives of ICCVAM member agencies to develop  metrics that the agencies could use to assess the progress they have  individually or collectively made toward reducing, refining, or replacing  animal use in testing and (2) incorporate those metrics into the  committee’s biennial progress reports. (Recommendation 1)

We provided a draft of this report to HHS, USDA, and EPA. HHS provided  written comments on the draft, which are presented in appendix I. In its  written comments, HHS stated that NIH concurred with our  recommendation. NIH further commented that ICCVAM’s activities in  support of promoting alternatives for animal use in testing do not extend  to animal use in any other context, such as research or training. NIH  explained that our use of the terms research and researcher to refer more  generally to research, testing, teaching, or experimentation could cause  misunderstanding. We understand that ICCVAM’s activities are focused  on animal use in product testing. In addition, we intended our  recommendation that the Director of the National Institute of  Environmental Health Sciences facilitate the establishment or designation  of an ICCVAM workgroup to be focused on product testing rather than on  other types of animal research. However, for editorial reasons, we did not  modify our report’s use of the terms research or researcher.

HHS and EPA also provided technical comments, which we incorporated  as appropriate. Among those comments, HHS’s FDA officials stated that  the agency encourages the use of alternatives to animal testing and  supports the principles of replacement, reduction, and refinement, but if  no alternative exists, animal testing may be the most appropriate way to  meet certain regulatory requirements to ensure the safety and efficacy of  medical products.

In its technical comments, EPA cited a September 2019, memorandum  EPA’s Administrator issued after we sent our draft report to the agencies  for comment. The memorandum commits the agency to take several  steps to reduce, replace, and refine animal testing requirements. For  example, the Administrator committed EPA to reducing its requests for,  and funding of, whole and live mammal studies by 30 percent by 2025  and eliminating all mammal study requests by 2035. We acknowledge  EPA’s announcement but did not assess it in our review of federal efforts  to facilitate the use of alternative research methods.

We are sending copies of this report to the appropriate congressional  committees, the Secretary of Agriculture, the Secretary of Health and  Human Services, the Administrator of the Environmental Protection  Agency, and other interested parties. In addition, the report will be  available at no charge on the GAO website at http://www.gao.gov.

If you or your staff members have any questions about this report, please  contact us at (202) 512-3841 or morriss@gao.gov or  neumannj@gao.gov. Contact points for our Offices of Congressional  Relations and Public Affairs may be found on the last page of this report.  GAO staff who made key contributions to this report are listed in appendix  II.

Appendix I: Comments from the Department of Health and Human Services

Appendix II: GAO Contact and Staff Acknowledgments

In addition to the individuals named above, Joseph Cook (Assistant  Director), Rodney Bacigalupo, Kevin Bray, Ross Campbell (Analyst-in- Charge), Tara Congdon, Hayden Huang, Amber Sinclair, and Kari Terrio  made key contributions to this report.

Researchers often use animals to study disease, test product safety, experiment, or teach. Some uses cause animals pain or distress. Federal agencies require researchers to consider alternatives to animal use, such as computer modeling or working with cell cultures.

The Department of Health and Human Services and other agencies have developed animal use alternatives and collaborate on these efforts in an interagency group. However, the agencies don’t routinely measure the effect of those efforts. We recommended that HHS create a workgroup to help agencies assess and report on their progress in reducing or replacing animal use in research.