Participants of a symposium held this week to mark the tenth anniversary of the Interagency Coordinating Committee on the Validation of Alternative Methods, or ICCVAM, unveiled a five-year plan to further reduce, refine, or replace the use of animals in research and regulatory testing.
The plan, available here, identifies priority areas for research, development, translation, and validation activities necessary to achieve regulatory acceptance of alternative in vitro testing methods, such as high-throughput screens, said an ICCVAM official.
“It’s my personal view, and I know that it is shared by others, that eventually we will completely eliminate animal testing,” said William Stokes, director of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, or NICEATM.
“If you look at the rate at which our knowledge is growing, we now know how cells work at the molecular level, we know how cells interact with each other, and we have the whole [human] genome mapped,” he said. “By understanding all of those interactions, we can now look at how chemicals perturb those critical cellular pathways and lead to toxicity.”
Stokes did point out, however, that the scientific community has an incredible amount of knowledge left to gain before it can completely understand those cellular pathways and understand that when chemicals or compounds have a sufficient level of toxicity at a given dose, they actually cause adverse effects.
A report just issued by the National Academy of Sciences called “Toxicology Testing in the 21st Century: A Vision and a Strategy” lays out a vision for significantly decreasing researchers’ dependence on animal testing, Stokes said. He also said that the NAS envisions a future where toxicology testing does not require, or very rarely requires, animal testing.
An integral part of the plan is to work with the pharmaceutical and biotech companies and other US and international stakeholders to accept and use alternative methods, Marilyn Wind, ICCVAM chair and the deputy associate director of the Consumer Products Safety Commission, told CBA News this week.
“Our first challenge [when developing the plan] was to identify priority areas for the next five years,” said Wind. ICCVAM looked at the kinds of tests that the member federal agencies require, and identified which tests are required by multiple agencies.
ICCVAM also looked at whether the test methods actually “refine, reduce, or replace animal testing,” Wind said. She also said that the committee determined which tests are used the most and should be replaced first.
“Using those criteria, we came up with our four highest priority testing areas, which were tests for ocular toxicity, dermal toxicity, acute systemic toxicity, and tests for biologics such as vaccines,” Wind said.
Other priority testing areas that use animals are studies of neuro and immunotoxicity, endocrine disruption, pyrogenicity, reproductive and developmental toxicity, chronic toxicity, and carcinogenicity, said Wind.
The second challenge is to incorporate new science and technology, said Wind. She said that ICCVAM wants to take advantage of new in vitro test methods and approaches currently in development.
This … would … clue pharmaceutical companies in early on to certain toxicities that they are interested in, and want to prevent.”
“We recognize that some of these [methods] will require years to develop and validate, and others will be available for use more quickly,” she said. “To meet that challenge, we will be working with federal agencies and other stakeholders so that can we can link the research and development activities to the standardization and validation of alternative test methods.”
The third challenge is fostering the acceptance and use of these alternative methods by federal regulatory and research agencies, said Wind. Under the ICCVAM Authorization Act of 2000, the Committee has a responsibility to look at the validation status of new test methods. It is responsible for making recommendations to its member federal agencies, she said.
Under that act, the federal agencies then have 180 days to respond to ICCVAM and tell ICCVAM how they are going to implement the use of the particular test method that has been validated, and if they are not going to implement its use, why they do not plan to do so, said Wind.
The fourth challenge is to further develop partnerships and strengthen interactions with industry and other stakeholders. According to Wind, “We need to do that so that we can take the limited resources that we and others have and work together to further the goals of ICCVAM.”
ICCVAM and national and international stakeholders must minimize duplicate efforts and ensure that information is exchanged at an early stage, so that the methods are developed, validated, and refined as early as possible, and that recommendations can be made for their use, Wind said.
Probably the areas most relevant to drug discovery are some of the research and development activities that are ongoing in the federal agencies, said Stokes.
“For example, we have a high-throughput screening initiative that we are doing in conjunction with the National Institutes of Health Chemical Genomics Center,” he said.
This project involves screening thousands of chemicals for various types of biological activity in human cells, primarily, although it does use some animal cells, and generating a profile of that biological activity. Stokes explained these profiles will allow researchers to look for patterns that are associated with toxicity.
“While the pharmaceutical industry has for many years run high-throughput screens looking for biological activity that may be relevant to pharmaceutical products, this is using that same approach to identify potential toxicities,” he said.
NICEATM and the NCGC hope that this initiative will identify predictive biomarkers that they can use for prioritizing chemicals for testing and making a preliminary assessment of their potential toxicity, said Stokes.
“What this would do for drug development is clue pharmaceutical companies in early on to certain toxicities that they are interested in, and want to prevent,” Wind said. The predictive biomarkers would be early biomarkers, and the companies would not have to wait until their drugs were going through preclinical trials to suddenly discover that toxicities that had not yet been identified were associated with the compounds.