Interagency Coordinating Committee on the Validation of Alternative Methods:

A Missed Opportunity or Potential For Progress?

By Nina Mak, AAVS Research Analyst &
Nicole Perry, AAVS Outreach Coordinator

In 1993, Congress recognized the growing need for scientifically sound alternatives to animal testing when it drafted the Revitalization Act of the National Institutes of Health (NIH). NIH, the primary federal agency directing medical research in the U.S., acts under the auspices of 27 Institutes and Centers, the majority of which utilize animals in their research. However, under the NIH Revitalization Act of 1993, one such institute was charged with creating a plan for certifying alternative toxicological testing methods and promoting acceptance of these methods within the scientific community.^[1]

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) was born in September of 1994 as an ad hoc committee of the National Institute of Environmental Health Sciences (NIEHS).^[2] Composed of representatives from 15 federal agencies, the committee worked for nearly two years publishing a report to fulfill its mandate. “Public concern about animal use,” they wrote, “…has resulted in recent legislation requiring scientists to consider, prior to using animals, alternatives that do not use animals, that reduce the number used, or that minimize their pain and distress.”^[3] Upon completion, this report outlined a process for validating alternative methods in a way that was designed to be useful to the scientific community at large.

With the release of its final report, titled “Validation and Regulatory Acceptance of Toxicological Test Methods,” ICCVAM was established as a standing committee in 1997.^[4] Using its report as an outline, ICCVAM was responsible for implementing its proposed plan.

Finally, with the enactment of the ICCVAM Authorization Act of 2000, the standing committee graduated to permanence under the National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).^[5] The law was enacted “[t]o establish, wherever feasible, guidelines, recommendations, and regulations that promote the regulatory acceptance of new or revised scientifically valid toxicological tests that protect human and animal health and the environment while reducing, refining, or replacing animal tests and ensuring human safety and product effectiveness.”^[6]

The law named 15 agencies as members of the Ccommittee, all of which are still involved, and designated a sixteenth category for “any other agency that develops, or employs tests or test data using animals, or regulates on the basis of the use of animals in toxicity testing.”^[7] Members of ICCVAM include representatives from the Agency for Toxic Substances and Disease Registry, Consumer Product Safety Commission, Department of Agriculture, Department of Defense, Department of Energy, Department of the Interior, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, National Institute for Occupational Safety and Health, National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences, National Library of Medicine, Occupational Safety and Health Administration.^[8]

In addition, the law created a Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) to advise ICCVAM and NICEATM on priorities related to developing, validating, and implementing alternatives. The law authorized a number of voting SACATM members, including at least one representative from a national animal protection organization.^[9]

Evaluation Process

ICCVAM was created with the purpose of reducing, refining, and replacing the use of animals in toxicological testing. One way that it attempts to do this is by sharing information among agencies to eliminate duplicate tests and harmonize testing practices. Another way is by evaluating proposed methods and communicating its findings to the public with press releases.

When a new method is proposed, peer review panels are convened, which must assess the usefulness and risk of the proposed method, eventually coming to a consensus on its validation status.^[10] Unfortunately, even if a method is validated, ICCVAM does not have the power to require agencies to adopt it.

Panels meet from time to time to discuss the evaluation process and suggest new procedures. These deliberations are conducted in public sessions with the opportunity for public comment.^[11]

However, ICCVAM's process for reviewing alternatives has been cumbersome and slow. There is growing frustration within the animal protection community, industry, and the general public with how ICCVAM operates, and many feel that significant changes are needed. Such dissatisfaction is not surprising when one looks at ICCVAM’s track record for the development, validation, and acceptance of alternatives.

In the 10 years since ICCVAM has been in existence, it has initiated and completed the validation of just three test methods.^[12] Another five test methods validated by the European Centre for the Validation of Alternative Methods (ECVAM) have been or are being reviewed by ICCVAM. The review processes have been invariably long and resource-consuming yet have resulted in only limited acceptance of the alternative methods in the best cases.^[13]

In the meantime, another 13 test methods have been endorsed by ECVAM’s Scientific Advisory Committee (ESAC), none of which have yet been reviewed by ICCVAM. In contrast, all three of ICCVAM’s validated methods have been quickly endorsed by ESAC.^[14]

While ECVAM is applying enormous resources and making great strides in Europe, many people are questioning why ICCVAM has not made similar progress. The animal welfare community was initially enthusiastic about the formation of ICCVAM and, in fact, instrumental in encouraging Congressional support for its establishment, but AAVS and others now have serious concerns about ICCVAM’s ability to advance alternatives adequately to meet the urgent challenge for a new testing paradigm that does not use animals.

ICCVAM’s Five-Year Plan

In 2006, the Congressional Appropriations Committee asked NICEATM/ICCVAM to create a Five-Year Plan outlining how it will advance the use of alternatives in the U.S.^[15] NICEATM/ICCVAM needs to seize this opportunity to re-strategize and develop new approaches to create a path forward for alternatives.

NICEATM/ICCVAM proceeded by gathering information from its member agencies and the public to aid in the formulation of the Five-Year Plan (the Plan), due by November 15, 2007.^[16] It announced that a Draft Plan was available for public comment on May 7, 2007.^[17]

AAVS and our affiliate, the Alternatives Research & Development Foundation (ARDF), reviewed ICCVAM’s Draft Plan and attended several public meetings discussing the Plan. The Draft Plan as presented, unfortunately, did little to alleviate our concerns with ICCVAM. Instead, it was a compilation of ICCVAM’s past activities, with indications that it will do more of the same. Given that these approaches have not been demonstrated to be effective during the past decade, there is no reason to believe they will be more successful in the future.

AAVS and ARDF submitted comments with several other animal protection groups detailing our concerns and suggestions for improvement.^[18] Even ICCVAM’s own Scientific Advisory Committee (SACATM) expressed significant concerns with the Draft Plan, encouraging ICCVAM to use this opportunity to take leadership in the alternatives field.^[19]

ICCVAM’s Priority Areas

The Draft Five-Year Plan begins by outlining four key challenges, which include:

Identifying priorities and conducting and facilitating alternative test method activities.
Incorporating new science and technology.
Fostering regulatory acceptance and use of alternative methods.
Developing partnerships and strengthening interactions with ICCVAM stakeholders.^[20]

AAVS, as well as other organizations and animal advocates, fully supports the strengthening of ICCVAM relationships, particularly regarding the sharing of resources and scientific expertise, maximizing validation efficiency, and minimizing duplication of tests.

Next, ICCVAM identified priority areas on which to focus its efforts for the next five years. Based on the potential impact on reducing, refining, or replacing animals for testing; applicability to multiple agencies; and potential to provide improved prediction of adverse health or environmental effects, ICCVAM selected eight different toxicity testing areas:^[21]

Acute Toxicity – Measures hazards arising from accidental exposure to a substance, either from ingestion, inhalation, or contact on skin.
Ocular Toxicity – Measures ability of a substance to cause temporary or permanent eye damage.
Biologics/Vaccines – Measures vaccine potency.
Dermal Toxicity – Measures ability of a substance to cause temporary or permanent skin irritation/damage.
Immunotoxicity – Measures ability of a substance to cause an allergic reaction, particularly when applied to the skin.
Endocrine Disruption – Measures ability of a substance to interfere with the endocrine system (hormones).
Pyrogenicity – Measures ability of a substance or device to induce fever.
Chronic Toxicity/Carcinogenicity – Measures hazards arising from long-term exposure to a substance, particularly the substance’s ability to damage cellular DNA and/or cause cancer.

ICCVAM also identified Neurotoxicty Testing and Reproductive and Developmental Toxicity Testing as areas of interest.

ICCVAM’s plan, however, fails to provide any overview, description, or analysis of how the above criteria apply to its stated priorities. For example, the Plan gives no indication of how many animals are used in each testing area and would therefore be spared by the alternatives work that ICCVAM is prioritizing. There is also no indication of which agencies require what kind of testing and when. There is also no indication of the ability of the animal tests currently used to predict adverse health or environmental effects.

This kind of information is basic and necessary if alternatives are going to be developed and adopted in any coordinated and meaningful way. Yet such information is exceedingly difficult to obtain in the U.S., and this lack of transparency is just one reason why alternatives research here has lagged behind Europe.

The Draft Plan continues with a list of activities that ICCVAM plans to pursue in each of its identified priority areas. However, the Plan provides no indication that ICCVAM will conduct its activities in any way that will improve its past underperformance in advancing alternatives in the U.S.

Recommendations for Advancing the Use of Alternatives

In general, progress in the European Union (EU) on developing and validating alternatives for toxicity testing has far surpassed the U.S. AAVS, ARDF, and several other animal protection organizations want ICCVAM’s Five-Year Plan to include an expedited review process so that it can act swiftly to take advantage of the progress that has been made in the EU, rather than going through the long, duplicative, and largely ineffective approach currently used by ICCVAM.

The Plan also needs to demonstrate that ICCVAM will focus more of its resources on the development and adoption of alternatives that will lead to the replacement of animals in toxicity tests, rather than just refinement and reduction alternatives. Given the limited resources it has, ICCVAM would be a far more effective leader in the alternatives field if it made replacement a priority.

In addition to the feedback provided by AAVS and other animal protection organizations, ICCVAM received several other constructive criticisms on its Draft Plan. These included a call for ICCVAM to specify clearly defined deliverables with timelines so that the Plan can serve as a blueprint for moving forward. It was also suggested that ICCVAM should implement a web-based scorecard to clarify the development and validation process for each alternative under review and to track the progress being made.^[22]

SACATM’s Five-Year Plan Working Group (FYPWG) delivered a critical analysis of ICCVAM’s Plan and identified several ways in which the Plan could be made stronger and more useful. The FYPWG echoed many of the same observations and suggestions made by the animal protection community, including an emphasis on the need for a more comprehensive Plan, the need to describe how priority criteria apply to testing areas, and the need for a Plan that addresses the frustrations felt by many stakeholders with the slow pace of progress being made by ICCVAM.^[23]

The FYPWG specifically stated that, “the Draft Five-Year Plan falls short in articulating a clear vision and strategic perspective,” and suggested that ICCVAM open a dialogue with the scientific, stakeholder, and regulatory committees to identify barriers to progress and ways to overcome them. The FYPWG further suggested that ICCVAM move its focus beyond research and development activities and more towards activities that will lead to translation, validation, and adoption of alternatives by regulatory agencies. The FYPWG also called on ICCVAM to “fully embrace the 3Rs and exert the leadership needed….”^[24]

Summary

It is clear that ICCVAM’s Draft Five-Year Plan fell short of the hopes and expectations of many for a comprehensive, specific plan that outlines how ICCVAM will advance alternatives in the U.S. and that will have a maximal impact on replacing and reducing animal use.

However, ICCVAM expressed its intention to take the suggestions made by the animal protection community, SACATM, and other stakeholders into consideration. The Final Five-Year Plan has the potential to make substantive changes to ICCVAM operations in order to accomplish more meaningful and rapid progress in the alternatives field, which was the intent of Congress in establishing ICCVAM.

AAVS and our affiliate, ARDF, will continue to monitor ICCVAM’s activities and work to boost the promotion and adoption of alternatives to animal use by ICCVAM and federal agencies. This is a long and tedious struggle, but AAVS and ARDF are committed to advocating for the implementation of non-animal methods in research and testing.

Citations

[1] Pub. L. No. 103-43 (1993).
[2] ICCVAM website. About the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Retrieved July 23, 2007, from http://iccvam.niehs.nih.gov/about/about_ICCVAM.htm.
[3] ICCVAM. “Validation and Regulatory Acceptance of Toxicological Test Methods: A report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods.” Retrieved on August 7, 2007, from http://iccvam.niehs.nih.gov/about/about_ICCVAM.htm.
[4] See supra note 2.
[5] See supra note 2.
[6] Pub. L. No. 106-545, 114 Stat. 2721 (2000).
[7] See supra note 6.
[8] See supra note 6.
[9] The current representative from an animal advocacy group is Dr. June Bradlaw of the International Foundation for Ethical Research. National Toxicology Program website. SACATM Members (February, 2007). Retrieved August 7, 2007, from http://ntp-server.niehs.nih.gov.
[10] See supra note 2.
[11] See supra note 2.
[12] Public comments filed June 7, 2008 by Humane Society Legislative Fund on behalf of Doris Day Animal League, Humane Society Legislative Fund, People for the Ethical Treatment of Animals, Physicians Committee for Responsible Medicine, Alternatives Research & Development Foundation, and American Anti-Vivisection Society regarding Draft NICEATM-ICCVAM Five-Year Plan (2008-2012) (72 FR 23832). Available at http://iccvam.niehs.nih.gov/pubcomment/5YP_draft/HSLF-ICCVAM5YrPlan.pdf.
[13] See supra note 12.
[14] See supra note 12.
[15] ICCVAM/NICEATM. “The NICEATM-ICCVAM Five-Year Plan (2008-2012). Draft: May 4, 2007.” Available at: http://iccvam.niehs.nih.gov/docs/about_docs/5YRPlan04May07FD.pdf.
[16] See supra note 15.
[17] 72 FR 23832; May 1, 2007.
[18] See supra note 12.
[19] SACATM Working Group for the NICEATM-ICCVAM Five-Year Plan (2007). “Review of the Draft NICEATM-ICCVAM Five-Year Plan.” Available at: http://ntp.niehs.nih.gov.
[20] See supra note 15.
[21] See supra note 15.
[22] Scala, R. (2007). “NICEATM-ICCVAM Town Meeting Summary.” Presented June 12, 2007 at SACATM Meeting. Available at http://iccvam.niehs.nih.gov/meetings/5YPlanTM/TownMtgSum11Jun07fD-dw.pdf.
[23] See supra note 19.
[24] See supra note 19.

Mak, Nina. Perry, Nicole. (Fall 2007). AV Magazine. Pages 4-7.

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