Ruminations on ICCVAM/NICEATM and the Draft NICEATM-ICCVAM Five-Year Plan (2008-2012)

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Programs & Policies - US

Ruminations on ICCVAM/NICEATM and the Draft NICEATM-ICCVAM Five-Year Plan (2008-2012)

Leonard Schechtmann, Innovative Toxicology Consulting, LLC

Published:December 6, 2007

About the Author(s)
Dr. Leonard Schechtman is President of Innovative Toxicology Consulting, LLC, where he serves as principal consultant in the area of research, development, translation, validation, regulatory acceptance and implementation of alternative toxicological test methods. He serves in a liaison capacity between test method developers, stakeholders and government agencies and interfaces with Federal regulatory agency personnel regarding issues involving alternative test methods, their evaluation, regulatory applicability, acceptance and implementation. He also serves on national and international science advisory committees and boards in the alternative test methods and validation arena and is a member of validation management teams established by such international organizations as ECVAM and JaCVAM.

Prior to establishing his independent consulting firm, Dr. Schechtman was Deputy Director for the US Food and Drug Administration (FDA) National Center for Toxicological Research (NCTR), Washington Operations, where he directed its scientific, administrative, intra-agency, inter-agency and international liaison activities. He also served as Chairperson of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and was the FDA Principal Representative and Agency Spokesperson to the ICCVAM. He was also the FDA/NCTR Representative to the Organization for Economic Cooperation and Development (OECD). Dr. Schechtman served as Executive Secretariat of the Scientific Advisory Board of the NCTR and as Executive Secretariat of the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants (Ranch Hand [Agent Orange] Advisory Committee, RHAC). He also served on the scientific advisory boards and committees of external national and international organizations responsible for the development and validation of new, improved, or surrogate alternative testing methods that have potential regulatory utility. He has been a member of the Scientific Program Planning Committees for the 4th, 5th and 6th World Congresses on Alternatives and Animal Use in the Life Sciences and has served as a member of the Organizing Committee for the 6th World Congress held in Japan in 2007. In addition, throughout his professional career, Dr. Schechtman has had the honor of serving as co-organizer, co-chair, rapporteur, and invited speaker at numerous other national and international scientific conferences, symposia, workshops, panels, and continuing education courses.

Over his 22+ year career at the FDA, Dr. Schechtman, in addition to his position as Deputy Director of FDA/NCTR, was also previously Associate Deputy Director for the Washington Office of FDA/NCTR, Senior Science Advisor in the Office of Testing and Research (OTR) at the FDA Center for Drug Evaluation and Research (CDER), and Senior Regulatory Review Scientist in toxicology with sub-specialty in genetic toxicology in the FDA Center for Veterinary Medicine (CVM). He served for approximately 8 years as Rapporteur for Genotoxicity to the International Congress on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, a cooperative effort of the regulatory bodies and pharmaceutical industry in the United States, the European Union, and Japan.

Prior to joining FDA in 1985, Dr. Schechtman worked in the private sector as a member of the senior scientific staff of Microbiological Associates, Inc., Bethesda, Maryland, where he was Director of its Genetic Toxicology Testing Program and Director of Genetic Toxicology Research and Development.

Dr. Schechtman received his B.S. degree in Biology from Long Island University, Brooklyn, New York, his M.S. degree in Cell Biology from the University of Cincinnati, Cincinnati, Ohio, and his Ph.D. from The Johns Hopkins University, Baltimore, Maryland, in Radiological Sciences and Pathobiology.

Leonard M. Schechtman, Ph.D.
President, Innovative Toxicology Consulting, LLC
9735 Via Verga St.
Lake Worth, FL 33467-6162

The ICCVAM 5-Year Plan was drafted in response to a request from the U.S. House and Senate Appropriations Committees. That request called for ICCVAM and its scientific/administrative support unit, NICEATM, in partnership with relevant Federal agency program offices, to build on the NTP Roadmap (A National Toxicology Program for the 21st Century:

Roadmap to Achieve the NTP Vision) and create a 5-Year Plan. To that end, the partners were to:

  • research, develop, translate, and validate new and revised non-animal and other alternative assays for integration of relevant and reliable methods into the 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 3Rs when this is scientifically valid and appropriate.

The NTP Roadmap acknowledges the need to, “Develop and validate improved testing methods and, where feasible, ensure that they reduce, refine, or replace the use of animals.” The Roadmap further states, “Activities and assays developed under the NTP Roadmap will be done in cooperation and consultation with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to maximize their value to regulatory agencies.”

Currently, the Plan is in draft form (draft of May 4, 2007), having been made available for no less than five opportunities for public comment, one of which was a “Town Meeting” held June 11, 2007. Once finalized and endorsed by ICCVAM and its respective agencies, the Plan is to be submitted to the NIEHS Budget Office for clearance and subsequently submitted to the House and Senate Appropriations Committees by November 15, 2007 per the congressional directive. The final Plan should be made publicly available in December 2007.

The draft Plan has provoked numerous public comments, some favorable and supportive and others critical. Some comments suggested that the Plan (a) may not have gone far enough and missed out on an opportunity to develop a new plan with which to move forward, (b) should provide for deliverables and offer a timeline, (c) includes familiar priorities, activities and approaches that have not changed over time and does not present new approaches, (d) lacks an explicit approach for addressing new science and technology, (e) should consider modifications to the test method evaluation process that would help avoid duplication of the efforts of other validation bodies and would render it more responsive to stakeholder needs, (f) ought to advance a more pro-active ICCVAM/NICEATM, (g) should have ICCVAM encouraging and facilitating the funding of research in alternative methods, (h) should provide for a “scorecard” for tracking progress.

It is not the intent of this commentary to debate all of the pluses and minuses of the Plan. However, a few of the issues and related matters are noteworthy. Before retiring from FDA at the end of 2006, I had served as FDA’s Principal Representative to ICCVAM for nine years and as its Chair for six years. Over that time period, I had the honor to have worked with all of the other agency representatives to ICCVAM and the NICEATM staff. These included conscientious, hard working, indefatigable professionals who are committed to ensuring the health of humans and animals and protection of the environment as well as fostering the refinement, reduction and replacement of animals used in research, education and testing. Despite their diligent efforts, their work has often been subjected to unwarranted criticism. These individuals deserve more accolades than they have heretofore received and should be recognized for the commendable and challenging job they are performing. They are dedicated individuals who devote their own time and energy, well beyond that of their everyday jobs, to promoting the principles of the 3Rs without compromising human, animal, and environmental health.

The ICCVAM/NICEATM validation process has been accused of being protracted and overly comprehensive to the detriment of having alternative test methods more readily available for regulatory use. Realistically, however, despite the emotional and political coercion to “get more alternative tests approved quicker,” the majority of them are “not ready for prime time” because they fail to satisfy the fundamental validation criteria of relevance and/or reliability to the degree required for credible regulatory decisions.

It is important to acknowledge that we are talking not only about the replacement, reduction and refinement of animal use, but also about the well-being of humans, animals and the environment. In light of that, the alternative tests used to determine the safe/hazardous nature of the products we consume and are exposed to had better be accurate and reliable indicators (as good as or better than existing tests) of the safe/hazardous nature of those agents and not give unacceptable levels of false negative and/or false positive results. Expeditious evaluations of the validity of alternative test methods rely on numerous factors, some of which originate with the submitter and the thoroughness of the information/data provided, and others of which rest with the validation bodies participating in the evaluation process. Expedited reviews, of course, would be ideal, but the reality is that good science must prevail in view of the terrible consequences of bad science; and more often than not, quick science tends to be bad science. If achieving the goal of reliability and accuracy requires more time, more retrospective and/or prospective studies (animal and/or non-animal), more exhaustive analyses, and more funding in the short term, then the ultimate attainment and implementation of the comparable or better test method will have been satisfied for regulatory decision-making purposes and will have been responsive to the 3Rs in the long term.

With regard to the NICEATM-ICCVAM 5-Year Plan, it builds suitably upon ongoing scientific activities and existing priorities. It offers some understanding into the establishment of those activities and priorities and describes the course of action for the continuation of those activities, many of which have already realized a significant investment in time and effort up to this point.

Unfortunately, however, the Plan does not consider much in the way of activities and priorities for the future beyond the initial 5 year period. It is lightly touched upon in the section on “Other Toxicity Areas of Interest” and more so in Chapter 2, “Advances in Science and Technology. However, the extent of ICCVAM/NICEATM input appears to be primarily that of monitoring those activities. Recognizing that, as its title suggests, the current Plan is, in fact, one that spans the next 5 years, it nevertheless would have been valuable for it to have offered some practical insight into the near future (e.g. the 5-year period beyond this one). The value added in providing the “bigger picture” would have been helpful to ICCVAM/NICEATM by envisioning “next steps” in the path forward and allowing ample time to plan for future endeavors while tackling the tasks before it in the immediate 5 years. By doing so, ICCVAM/NICEATM can be looking beyond the existing activities and priorities for the immediate 5-year period, and begin its exploration of new priorities, activities, test methods, strategies, etc. with an eye towards populating the repository of alternatives that ICCVAM/NICEATM should begin pursuing that would bridge the current 5 year plan and that of the 5 year plan to follow.

The Congressional call for the 5-Year Plan should have been viewed as an opportunity presented to ICCVAM/NICEATM to expand the scope of its activities and aim its sights on new directions and leadership possibilities that would help it fulfill its overall mission over the long term, not just the short term. One such new direction is to move beyond its role as facilitator and encourage the development and translation of alternative test methods with potential regulatory applicability by funding test developer R&D and translation efforts that would feed the pipeline of methods warranting validation. Additionally, establishing and staffing a laboratory of its own (akin to those of other international validation organizations) and participating directly in the conduct of “wet-bench” international validation studies as necessary would add to its global recognition beyond that of facilitator and test method evaluator. All this, of course, requires appropriate dollars and those monies should be specifically directed to and managed by NICEATM. Those funds should not be incorporated into the NIEHS/NTP budget to be doled out (or not) at the discretion of management. Those funds should be earmarked for the purposes of funding defined ICCVAM/NICEATM alternative test method activities expressly and not consumed for some amorphous NTP activities labeled as such. The entire process (growth and funding) needs to be removed from the political arena and operate solely on the basis of the science.

One avenue not considered by the Plan is that of a 5-Year Plan evaluation process. It would be appropriate to have some means of gauging ICCVAM/NICEATM progress relative to the challenges, milestones, and goals laid out in the Plan and to have the evaluation conducted for each 5-year period. Such an assessment would reflect such matters as progress, timeliness, successes, failures, shifts in priorities, need for redirection or refocusing as may be necessary, etc. This process could take on various different forms or be a combination of them. Examples include: (a) a facilitated self appraisal conducted by the members of ICCVAM/NICEATM, (b) an independent peer review by a select panel of experts (similar to scientific program evaluations that take place in federal agencies and in academic institutions), (c) an evaluation performed by stakeholders. This could also be an opportunity for ICCVAM/NICEATM to participate in a “360º evaluation” by providing feedback on such issues as (a) the level of cooperation and support it received from stakeholders, (b) the number and quality of nominations/submissions of potentially useful alternative test methods, (c) the extent of implementation of recommended validated tests by regulatory agencies, (d) the criticisms it received or did not receive from its stakeholders, which would include the animal welfare organizations, test developers, regulatory and research agencies, other validation organizations, industry, and academia.

The NICEATM-ICCVAM Five-Year Plan (2008-2012) is the first of its kind for ICCVAM/NICEATM since the inception of the organization. Despite the absence of such a formal document in the past, ICCVAM/NICEATM did codify its mission and vision, did have a defined set of purposes, aims and duties, did have a strategic plan, did set scientific goals, and has been guided by numerous publications, documents and policies.

Some of these include:

Together, these factors have helped steer the scientific efforts of ICCVAM/NICEATM and have enabled them to make enormous strides in the identification, validation, and promotion of alternative test methods responsive to the 3Rs and useful for regulatory purposes in the protection of humans, animals, and the environment. The Plan is obviously a “living document”, one that will continue to evolve, expand, and improve with time. It deserves continued support, encouragement, and constructive input that will help move it to the next plateau.
©2007 Leonard Schechtmann