There has been ongoing progress in the development and validation of new alternative test methods. There are, however, many endpoints that still have no alternative methods available, such as neurotoxicity. ECVAM is currently evaluating in vitro tests for carcinogenicity.
Even when an alternative method is available for a specific endpoint, there may be situations when it cannot be used. This could be due to an incompatible form of the test substance, a chemical class that has not been evaluated in the alternative method, or the method may not be accepted for use by the regulatory agency to which data must be submitted.
To meet regulatory requirements in many cases, a number of in vitro methods might be required to replace one in vivo animal method. This adds to the complexity, making it difficult to determine how to combine the in vitro methods and analyze the resulting data.
Another problem area is the validation process itself, especially when many regulatory agencies still consider the “gold standard” to be animal test data and want to use this in evaluating a new test method. The results obtained from a new method must be quantitatively compared to the results from the corresponding animal test. Most scientists agree that it does not make sense to compare the results from a human cell-based assay to those of an animal test. For one thing, they are not measuring the identical biological event. Furthermore, the animal and human responses to chemicals are not always comparable. (And yet regulatory agencies still require these tests.)
In the U.S., even when an alternative test has been validated, individual regulatory agencies have the option to accept it as being relevant for regulatory purposes. Under this structure, the status-quo tends to take precedence and the newer validated methods have to exceed the currently accepted animal method for identifying safety and efficacy to be considered. Even if the assay has shown greater scientific relevance for human toxicity and safety assessment, a regulatory agency can continue to accept data from animal tests or even decide that the new test is not relevant for the agency’s use. As of this date, there are no planned mandates to require the use of validated alternatives instead of animal tests by U.S. regulatory agencies.
Stakeholders in the animal testing issue – scientists, regulators, industry and animal advocates – cannot agree on the criteria to prioritize the areas of greatest need for new alternative test methods. Animal advocates, for example, want this prioritization to be based on the number of animals used for a particular type of test. Regulatory agencies, on the other hand, are usually interested in prioritizing the most hazardous chemicals for testing, and are developing in vitro screening assays for this purpose.
Other barriers also exist to the immediate replacement of all of the animal tests with non-animal alternative methods. A greater allocation of resources will have to be channeled to efforts to develop and validate new methods, and industry and regulatory scientists alike will have to overcome resistance to change. Additionally, incentives to implement validated alternatives and policies that discourage continued acceptance of animal testing methods will have to be instituted for both industry and regulatory agencies. The greatest challenge is the scientific complexity of replacing some of the whole animal tests with cell and computational models. For example, the responses from animal-based systemic and reproductive toxicity tests involve many organ systems; each organ system involves various tissues and cell types, and the blood circulating among the tissues and organs; and within the cells are many molecular pathways that may vary considerably between species, cell types, organ source, and types and degree of toxic responses.