US Validation Center: ICCVAM and NICEATM

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United States: Programs & Policies

US Validation Center: ICCVAM and NICEATM

Last updated: August 28, 2014

Two government entities comprise the "national validation center" in the United States:

  • National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
  • Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

About NICEATM

NICEATM, established in 1998 to provide administrative, technical, and scientific support to ICCVAM, is an office within the Division of the NTP (DNTP) at the National Institute of Environmental Health Sciences (NIEHS), one of the National Institutes of Health.

NICEATM’s mandate was updated in 2013, and now additionally includes supporting DNTP activities, especially NTP participation in the interagency Tox21 initiative, and conducting computational analyses of data related to high-priority projects.

NICEATM is located in Research Triangle Park, North Carolina, and is staffed by Dr. Warren Casey, Director since January 2014, and NIEHS toxicologist Dr. Elizabeth Maull. Additional support is provided via a government contract, currently awarded to Integrated Laboratory Systems, Inc.

About ICCVAM

ICCVAM’s mission is to facilitate development, validation, and regulatory acceptance of new and revised regulatory test methods that reduce, refine, and replace the use of animals in testing while maintaining and promoting scientific quality and the protection of human health, animal health, and the environment.

ICCVAM was established as an ad hoc committee in 1994 in response to a mandate to the Director of the National Institutes of Health (NIH) under the NIH Revitalization Act of 1993 (Public Law 103-43, Sec. 205, pp. 25-27). Many of the activities specified under Sec. 205 (see Sec. 1301, p. 48) were assigned to the Director of NIEHS to:

  • expand knowledge of the health effects of environmental agents,
  • broaden the spectrum of toxicology information that is obtained on selected chemicals,
  • develop and validate assays and protocols, including alternative methods that can reduce or eliminate the use of animals in acute or chronic safety testing,
  • establish criteria for the validation and regulatory acceptance of alternative testing and to recommend a process through which scientifically validated alternative methods can be accepted for regulatory use,
  • communicate the results of research to government agencies, to medical, scientific, and regulatory communities, and to the public, and
  • integrate related activities of the Department of Health and Human Services.

The report, Validation and Regulatory Acceptance of Toxicological Test Methods (NIH Publication No. 97-3981), published in 1997 and modified in 2000, established the criteria and processes for the validation and regulatory acceptance of alternative test methods. Later in 1997, ICCVAM was designated as a standing committee by NIEHS.

In 2000, the ICCVAM Authorization Act (Public Law 106-545, 42 USC 285l-5) established ICCVAM as a permanent interagency committee of NIEHS composed of members from 15 Federal agencies. This Act explains the purpose of ICCVAM 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." This Act does not alter the previously designated authorities of the NIEHS Director regarding ICCVAM.

The ICCVAM Authorization Act directs ICCVAM to carry out the following duties:

  1. Review and evaluate new or revised or alternative test methods…that may be acceptable for specific regulatory uses, including [those]…of interagency interest.
  2. Facilitate appropriate interagency and international harmonization of acute or chronic toxicological test protocols that encourage the reduction, refinement, or replacement of animal test methods.
  3. Facilitate and provide guidance on the development of validation criteria, validation studies and processes for new or revised or alternative test methods and help facilitate the acceptance [and awareness] of such scientifically valid test methods.
  4. Submit ICCVAM test recommendations for the test method reviewed by ICCVAM…to each appropriate Federal agency…
  5. Consider for review and evaluation, petitions received from the public that (A) identify a specific regulation, recommendation, or guideline regarding a regulatory mandate; and (B) recommend new or revised or alternative test methods and provide valid scientific evidence of the potential of the test method.
  6. Make available to the public final ICCVAM test recommendations [that were sent to] Federal agencies and the [agency] responses….
  7. Prepare [biennial] reports to be made available to the public on [ICCVAM] progress under this Act.

ICCVAM includes representatives from the following 15 US regulatory and research agencies:

  • 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 Cancer Institute
  • National Institute of Environmental Health Sciences
  • National Institute of Occupational Safety and Health
  • National Institutes of Health
  • National Library of Medicine
  • Occupational Safety and Health Administration

Scientists from each of these agencies are appointed to serve as ICCVAM members because they are knowledgeable about their agency’s activities or requirements relevant to safety testing. ICCVAM members attend monthly ICCVAM committee meetings or teleconferences and engage in other ICCVAM activities in addition to their other duties within their agencies.

Scientific Advisory Committee

The ICCVAM Authorization Act established a Scientific Advisory Committee, now designated the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM), to advise ICCVAM and NICEATM regarding ICCVAM activities.

SACATM operates under the rules of the Federal Advisory Committee Act, and members are appointed by the NIEHS Director. SACATM is composed of representatives from various types of organizations specified in the Act, including certain industry sectors, the animal protection community, state government, academia, and test method developers. ICCVAM members who represent the 15 ICCVAM agencies serve as non-voting SACATM members.

Test Method Submission and Evaluation

ICCVAM’s criteria for evaluating the scientific validity of new or revised toxicity test methods and promoting their regulatory acceptance are specified in the following documents:

ICCVAM is currently revising its test method evaluation procedures, and provided AltTox with the following update:

ICCVAM depends on stakeholders with appropriate capabilities and resources to carry out alternative test method research, development, and validation studies; therefore, ICCVAM welcomes submissions of innovative test methods that may be acceptable for specific regulatory use. However, to maximize the potential for effective implementation of new test methods or approaches, ICCVAM will only conduct future evaluations and prepare recommendations on test method submissions proposed for regulatory uses that align with ICCVAM member agency needs and priorities. ICCVAM is currently revising its test method evaluation procedures, and stakeholders considering submission of test methods for evaluation are encouraged to contact ICCVAM.

To optimize utilization of resources and avoid duplication of effort, ICCVAM will also be coordinating future test method evaluation activities with partner organizations in the International Cooperation for Alternative Test Methods [see “International Activities” section below].

ICCVAM has evaluated 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 and vaccine potency; skin corrosivity, developmental toxicity, endocrine disruption, eye corrosivity and irritation, pyrogenicity, and allergic contact dermatitis/skin sensitization.

Tables that summarize past ICCVAM evaluations, and validation and regulatory acceptance of alternative toxicological test methods include:

International Activities

NICEATM and ICCVAM work with other validation centers to promote validation, acceptance, and international harmonization of test methods that reduce, refine, and/or replace animal methods.

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, the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), the Japanese Center for the Validation of Alternative Methods (JaCVAM), Health Canada, and the International Cooperation on Cosmetics Regulation (ICCR) collaborated to develop the framework for ICATM. The Korean Center for the Validation of Alternative Methods (KoCVAM) joined the ICATM in 2011. The ICATM agreement facilitates international 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.

The US National Coordinator for the Organisation for Economic Cooperation and Development (OECD) Test Guidelines Programme was added as an ex officio member of ICCVAM in 2013. The National Coordinator solicits and collates comments on draft test guidelines and other documents from ICCVAM members and other US stakeholders. The National Coordinator then represents the United States at the annual meeting of the National Coordinators of the Test Guidelines Programme and in other test guideline development activities.

ICCVAM Progress and New Direction

Both ICCVAM and NICEATM were reorganized in 2013. This section will provide some historical perspective on reporting of past accomplishments, and the new vision and direction for ICCVAM announced in 2013.

ICCVAM is required under the ICCVAM Authorization Act to provide biennial progress reports. The last ICCVAM Biennial Report was issued in July 2014 and summarizes activities during 2012 and 2013.

NICEATM-ICCVAM was also directed by Congress in 2007 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, and
  • 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 (2008-2012) identified the following key challenges:

  • Identify priority areas, and conduct and facilitate alternative test method activities in these priority areas.
    • Priority was identified as alternatives for regulatory tests that cause significant pain and distress and/or involve large numbers of animals = test methods for biologics/vaccines, ocular toxicity, dermal toxicity, and acute toxicity
  • Identify and promote incorporation of new science and technology.
  • Foster acceptance and appropriate use of alternative test methods.
  • Develop partnerships and strengthen interactions with international stakeholders.

A Five-Year Plan progress report was presented at the September 2012 SACATM meeting. The NICEATM-ICCVAM Update, provides a nice summary of ICCVAM progress up to the 2013 reorganization.

A draft NICEATM-ICCVAM Five-Year Plan (2013-2017) was developed in 2012, but this plan and related public comments do not have a link on the current ICCVAM webpage. The proposed 2013-2017 Plan was also presented at the September 2012 SACATM meeting.

The vision for the 2013 reorganization of ICCVAM is described on the NTP website, and in the draft document issued by ICCVAM, "A New Vision and Direction for ICCVAM." This document presents ICCVAM’s (1) areas of priority and scientific focus for immediate resource investment, (2) plans to improve communications with stakeholders and the public, and (3) interest in exploring new paradigms for the validation and utilization of alternative toxicological methods. It was released for public comment in August 2013, and discussed at the September 2013 SACATM meeting. ICCVAM is currently considering public and SACATM comments on the draft document as it develops new operating procedures and plans activities for the future.

Along with ICATM partners, ICCVAM is continuing to work on evaluating and advancing alternative methods for skin sensitization. ICCVAM evaluated the electrophilic allergen screening assay (EASA), submitted in 2012, and designated it a high priority. Additionally, NICEATM is collaborating with industry scientists "to create an integrated testing strategy to combine information from multiple testing methods to identify potential skin sensitizers." ICCVAM has established a Skin Sensitization Working Group to consider future activities in this area, which will be closely coordinated with ongoing EURL ECVAM activities.

A small and virtual peer review of a Summary Review Document (SRD) for the Short Time Exposure (STE) ocular irritation/corrosion test method was conducted in 2013. NICEATM reported that JaCVAM requested "ICCVAM conduct an international peer review of the STE test method," and that they "provided a final report to JaCVAM and the test method developer." Kao Corporation, the developer of the STE method, included the final SRD in a test submission package to the Organisation for Economic Cooperation and Development (OECD), and OECD made a draft test guideline (TG) available for public comment in November 2013. This new test method review, for some reason, circumvented the traditional approach of using a public peer review panel and the formulation of ICCVAM recommendation prior to OECD TG development.

NICEATM Activities and New Direction

NICEATM also underwent reorganization in 2013. This included personnel changes and relocation of the NICEATM and ICCVAM web presence to the NTP website. NICEATM has also been assigned additional NTP activities in addition to its original purpose as the administrative and scientific support for ICCVAM.

NICEATM provided AltTox with the following update of their activities as of August 2014:

NICEATM is conducting a number of projects supporting development and validation of high-throughput screening approaches. These projects focus on three key areas:

Details on these projects were presented at the 2014 Society of Toxicology meeting, and updates will be presented at the Ninth World Congress on Alternatives and Animal Use in the Life Sciences.

NICEATM is also working with external collaborators to organize workshops on alternative methods, including workshops on the use of aquatic models for toxicity screening and regulatory application of adverse outcome pathways.