Implementation of the NICEATM-ICCVAM Five-Year Plan

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Implementation of the NICEATM-ICCVAM Five-Year Plan

Published: July 28, 2009
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and its sister organization the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) released their Draft Implementation Plan for the NICEATM-ICCVAM Five -Year Plan (2008-2012) for discussion at the June 25-26, 2009 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) in Arlington, Virginia. The NICEATM-ICCVAM Five-Year Plan itself had been released in January 2008, in response to a Congressional mandate.

Dr. William Stokes, NICEATM Director, explained in a June 9 memo to the SACATM that ‘the draft [implementation] plan outlines the activities planned by ICCVAM to address the four challenges described in the Five-Year Plan, and highlights the status of those activities that have already been initiated.’

Dr. Suzanne Fitzpatrick, the U.S. Food and Drug Administration’s principal agency representative to the ICCVAM and Chair of the ICCVAM 5-year Plan Subcommittee, presented an overview of the draft implementation plan at the SACATM meeting. Dr. Fitzpatrick’s slides are available online and summarize the information provided in the draft implementation plan document itself.

The Draft Implementation Plan is a 20-page report that includes a brief description of the four challenges described in the Five-Year Plan, and NICEATM and ICCVAM’s ‘plans to implement the goals and objectives set forth for the next 5 years’ (p. 2). Appendix A, an additional 14 pages, is a table describing ‘ongoing and planned research, development, translation, and validation activities in ICCVAM member agencies relevant to test methods that reduce, refine, and replace the use of animals’ (pp. 21-34).

The Five-Year Plan identified 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
  • Challenge #2: Identify and promote incorporation of new science and technology
  • Challenge #3: Foster acceptance and appropriate use of alternative test methods
  • Challenge #4: Develop partnerships and strengthen interactions with international stakeholders

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.

In the implementation plan, NICEATM and ICCVAM describe their primary approach to this topic as ‘identifying critical knowledge and data gaps that need to be addressed in order to advance alternative methods for these and other priority areas’ (p. 3). NICEATM and ICCVAM also plan to work with stakeholders so that research and validation studies address regulatory testing needs, and ICCVAM will continue their key role in evaluating the validity of test method submissions.

The draft implementation plan identifies Specific Objectives and outlines Planned Activities for the priority toxicity testing areas. Dr. Fitzpatrick noted that priorities may vary across agencies and they may change over time. Relevant 2008-09 accomplishments are also summarized to highlight accomplishments toward the specific program goals.

Just one example of the plan’s content will be provided here. The implementation plan for biologics/vaccines testing was summarized as follows (Fitzpatrick, 2009):

Basis for High Priority:

  • Vaccine potency testing accounts for more animals experiencing pain and distress without analgesics, anesthetics, or tranquilizers on the US Department of Agriculture (USDA) annual report than any other testing procedure
  • Multiple regulatory agencies require such testing

Planned Activities include:

  • Developing a scientific workshop to evaluate:
    • The state of the science for possible alternatives
    • Use of humane endpoints in in vivo potency tests
  • Evaluate in vitro potency tests for Leptospirosis vaccines being developed by the USDA and Michigan State University

Accomplishments:

  • ICCVAM Biologics Working Group was reconstituted to address these activities
  • Workshop will be scheduled for 2010

Funding of extramural research and validation studies are essential for progress in these areas, so plans for how to promote agency extramural funding are an appropriate component of the implementation plan. While ICCVAM does not directly fund test method validation studies, NICEATM does have limited resources that can be used to support validation studies. Two examples would be the in vitro cytotoxicity test method validation study and the ongoing LUMICELL validation study. Given these limited resources for research, optimization, and validation of new test methods, it is essential that NICEATM and ICCVAM work with relevant agency Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs—especially the NIEHS’s—to develop announcements for specific SBIR/STTR topics to meet the ICCVAM priorities. SBIR funding was mentioned in the implementation plan in reference to refinements in the Bovine Corneal Opacity and Permeability (BCOP) assay. An SBIR/STTR program announcement was recently released by NIH that provides up to $850,000 per grant to develop in vitro alternative tests for the botulinum toxin potency assay. Other SBIR topics relevant to alternative methods can be located on the NIH and NIEHS websites.

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).

The two topics discussed under Challenge #2 in the implementation plan were nanomaterials testing and high-throughput screening. Other topics mentioned in the SACATM presentation as potentially applicable include: lower organism-based test systems, computational approaches, biomarkers of toxicity, and toxicology databases. Relevant NICEATM-ICCVAM tasks include monitoring agency and other research activities to identify useful approaches, as well as planning, monitoring, and facilitating a number of other activities.

Challenge #3: Foster acceptance and appropriate use of alternative test methods. This challenge describes communication-related activities ICCVAM will take to facilitate the acceptance and use of validated methods.

The implementation plan described the NICEATM-ICCVAM website as an example of addressing this challenge. The website was updated last year, and now provides easier access to documents. Reviewed methods and other information are now summarized in easily accessible tables. The updated website has achieved its goal of being more user-friendly. Another activity related to Challenge #3 mentioned in the SACATM presentation was that each of the 15 agencies participating with ICCVAM will have an alternatives/3Rs webpage on their website (or possibly on the ICCVAM website). This would have great utility for both intramural and extramural stakeholders by providing easy access to alternatives-related activities being conducted at each agency.

Challenge #4: Develop partnerships and strengthen interactions with international stakeholders. The five-year plan called for strengthened relationships with ECVAM (European Centre for the Validation of Alternative Methods) and other international stakeholders to enhance efficiencies.

A number of planned activities such as co-sponsoring workshops and participating in the development of draft OECD (Organization for Economic Development and Cooperation) Test Guidelines for validated methods were described in the implementation plan. Quite a few accomplishments in meeting this goal during 2008-09 were also described.
Opportunity for public written and oral comments on the draft implementation plan, which was characterized at the SACATM meeting as a living document, were provided in conjunction with the SACATM meeting. However, ICCVAM has indicated that they always welcome comments on any aspect of their activities, and they also welcome test method nominations and submissions from anyone at any time. Visit this ICCVAM page to submit your comments on the plan for implementing the five-year plan.