The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) are the two government entities that comprise the 'national validation center' for the United States.
The purpose of ICCVAM-NICEATM is "to 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."
About ICCVAM and NICEATM
The ICCVAM was established as an ad hoc committee in 1994 in response to a mandate to the National Institute of Environmental Health Sciences (NIEHS) under the NIH Revitalization Act of 1993 (Public Law 103-43) for the NIEHS to establish criteria for the validation and regulatory acceptance of alternative toxicological test methods, and to recommend a process for achieving regulatory acceptance of methods considered to be scientifically valid.
The report providing the requested information, Validation and Regulatory Acceptance of Toxicological Test Methods, was published in 1997 [and was modified in 2000]. Later in 1997, the ICCVAM was established as a standing committee by the NIEHS. In 2000, the ICCVAM Authorization Act (Public Law 106-545, 42 USC 285l-5) established the ICCVAM as a permanent interagency committee of the NIEHS.
The ICCVAM Authorization Act directs ICCVAM to carry out the following duties:
- Coordinate the technical review and evaluation of new and revised test methods
- Submit ICCVAM test recommendations to appropriate US Federal agencies
- Facilitate interagency and international harmonization of test protocols that encourage the reduction, refinement, and replacement of animal test methods
- Facilitate and provide guidance on validation criteria and processes
- Facilitate the acceptance of scientifically valid test methods
- Facilitate awareness of accepted test methods
- Consider petitions from the public for review and evaluation of new and revised test methods for which there is evidence of scientific validity
- Make ICCVAM final test recommendations available to the public
- Prepare reports on ICCVAM progress and accomplishments under the Act and make these available to the public
The following 15 US Federal regulatory and research agencies make up the ICCVAM:
- Agency for Toxic Substances and Disease Registry (ATSDR)
- Consumer Product Safety Commission (CPSC)
- Department of Agriculture (USDA)
- Department of Defense (DoD)
- Department of Energy (DOE)
- Department of the Interior (DOI)
- Department of Transportation (DOT)
- Environmental Protection Agency (EPA)
- Food and Drug Administration (FDA)
- National Cancer Institute (NCI)
- National Institute of Environmental Health Sciences (NIEHS)
- National Institute of Occupational Safety and Health (NIOSH)
- National Institutes of Health (NIH)
- National Library of Medicine (NLM)
- Occupational Safety and Health Administration (OSHA)
Representatives from each of these agencies are appointed as members who represent their agencies on the ICCVAM.
The NICEATM was established in 1998 to provide administrative, technical, and scientific support to ICCVAM. This support includes the review of test method nominations, organization of peer review panels and workshops, and communication with ICCVAM stakeholders. NICEATM also conducts evaluations of test method submissions for completeness, for adherence to ICCVAM guidelines, and for suitability for ICCVAM evaluation. NICEATM may also sponsor validation studies as resources permit.
NICEATM is located at the NIEHS, Research Triangle Park, North Carolina. Dr. William Stokes is the Director of NICEATM as well as the Executive Director of ICCVAM. NICEATM recently appointed Dr. Warren Casey as Deputy Director. Their Special Assistant is Ms. Deborah McCarley. Contractors employed by Integrated Laboratory Systems, Inc. provide support for NICEATM projects.
Scientific Advisory Committee
Pursuant to the ICCVAM Authorization Act, a Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) was created to advise ICCVAM, NICEATM, and the NIEHS director regarding "priorities and activates related to the development, validation, scientific review, regulatory acceptance, implementation, and national and international harmonization of new, revised, and alternative toxicological test methods." The SACATM operates under the rules of the Federal Advisory Committee Act and is required to include representatives from state government, academia, industry, and the animal protection community.
Test Method Evaluation, Validation, and Regulatory Acceptance
ICCVAM's criteria for evaluating the scientific validity of new or revised toxicity test methods and promoting their regulatory acceptance have been articulated in the following documents:
Test method validation and regulatory acceptance are further described in these sections of AltTox: Validation and Regulatory Acceptance.
Scientists at agencies and organizations external to NICEATM-ICCVAM typically conduct validation studies of new or revised toxicity test methods, or submit nominations for the review of an existing method/data to NICEATM. NICEATM assesses submissions and nominations and forwards their recommendations to the ICCVAM. If a method/submission is deemed ready, an independent scientific peer review panel reviews the data and makes recommendations on its scientific validity to the ICCVAM. The ICCVAM then develops recommendations on the scientific validity of the method and forwards its recommendations to regulatory agencies for their review and acceptance.
ICCVAM has evaluated [or is in the process of evaluating] toxicity test methods that have the potential to reduce, refine, and/or replace animals in testing for the following toxicological endpoints: acute systemic toxicity; biologics/vaccine potency; developmental toxicity; endocrine disruption; eye irritation and corrosion; genetic toxicity; pyrogenicity; skin corrosion; and skin sensitization.
ICCVAM is required by law to provide biennial progress reports. The most recent report is the Biennial Progress Report, 2008–2009. One of the highlights of this reporting period was the 2008 acceptance by US agencies of two in vitro ocular toxicity test methods (BCOP and ICE) previously endorsed by ICCVAM for determining the ocular corrosive potential (irreversible eye injury) of chemicals and products; these methods were then adopted as international OECD test guidelines in 2009. NICEATM participated in drafting the OECD test guidelines.
The NICEATM-ICCVAM website provides the following tables that summarize their validation and regulatory acceptance activities to date: Summary of Test Methods Evaluated or Under Consideration by ICCVAM; US and International Acceptance of Alternative Methods, 1998-2010 Chronological List; Nominations and Submissions; and Alternative Test Method Project Milestones.
International Activities
NICEATM and ICCVAM have worked with the other validation centers, the European Centre for the Validation of Alternative Methods (ECVAM) and the Japanese Centre for the Validation of Alternative Methods (JaCVAM), and with other international organizations such as the Organisation for Economic Cooperation and Development (OECD) over the past decade to promote validation, acceptance, and international harmonization of test methods that reduce, refine, and/or replace animal methods. However, differences in processes, structure, communications, and resulting recommendations among the different organizations did not always provide for final agreement on regulatory acceptance.
To further facilitate international cooperation and progress, representatives from agencies of the United States, the European Union, Canada, and Japan signed a Memorandum of Cooperation to establish the International Cooperation on Alternative Test Methods (ICATM) in April 2009. The goal of the ICATM agreement is to promote "international cooperation and coordination on the scientific validation of non- and reduced-animal toxicity testing methods." ICCVAM, ECVAM, JaCVAM, Health Canada, and the International Cooperation on Cosmetics Regulation (ICCR) worked in collaboration to develop the framework for ICATM. The ICATM agreement should further enhance international cooperation among the national validation centers by facilitating collaboration and coordination on validation studies, peer reviews, and the development of test method recommendations, all of which should encourage greater harmonization in the acceptance of new and scientifically valid toxicity test methods.
NICEATM-ICCVAM Five-Year Plan
In 2007, NICEATM-ICCVAM was directed by Congress to develop a Five-Year Plan to:
- Research, develop, translate, and validate new and revised non-animal and other alternative assays for integration of relevant and reliable methods into Federal agency testing programs
- Identify areas of high priority for new and revised non-animal and alternative assays or batteries of those assays to create a path forward for the replacement, reduction, and refinement of animal tests, when this is scientifically valid and appropriate
The NICEATM-ICCVAM Five-Year Plan identifies four key challenges to be addressed during the next five years. These are:
Challenge #1: Identify priority areas and conduct and facilitate alternative test method activities in these priority areas. Priority areas were designated in the five-year plan based on the desire of ICCVAM to emphasize alternatives for regulatory tests that can cause significant pain and distress and/or involve large numbers of animals. The highest priority areas are test methods for biologics/vaccines, and ocular, dermal, and acute toxicity.
Challenge #2: Identify and promote incorporation of new science and technology. The Five-Year Plan calls for NICEATM-ICCVAM to identify and promote the development of technologies that will eventually translate into alternative methods. This challenge involves communication with Federal agencies regarding their research and other activities relevant to test methods that could reduce, refine, or replace animal test methods. ICCVAM working groups will interact with test developers to optimize efforts toward meeting regulatory needs. An ICCVAM Research and Development Working Group has been established to 'help identify test methods in the development phase that would benefit from referral and interaction with an ICCVAM test method working group' (p. 12).
Challenge #3: Foster acceptance and appropriate use of alternative test methods. This challenge describes communication-related activities ICCVAM will undertake to facilitate the acceptance and use of validated methods.
Challenge #4: Develop partnerships and strengthen interactions with international stakeholders. The Five-Year Plan called for strengthened relationships with ECVAM and other international stakeholders to enhance efficiencies.
A "Draft Implementation Plan for the NICEATM-ICCVAM Five-Year Plan" was published in June 2009 to address the concerns noted by Congress about the pace of progress. The Draft Implementation Plan was reported at the June 2009 SACATM meeting, and ICCVAM's responses provided to each of the challenges of the Five-Year Plan have been described in an AltTox Spotlight article.
NICEATM and ICCVAM are working to keep stakeholders advised of their progress toward meeting the challenges set forth in their Five-Year Plan through updates to their website and presentations at scientific and government meetings.
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