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A Real-time Evaluation of Human-based Approaches to Safety Testing: What We Can Do Now (TDS)
Citation:
Houck, K., R. Coleman, K. Tsaioun, AND K. Archibald. A Real-time Evaluation of Human-based Approaches to Safety Testing: What We Can Do Now (TDS). Presented at ToxCast Data Summit, RTP, NC, September 29 - 30, 2014. https://doi.org/10.23645/epacomptox.5193409
Impact/Purpose:
Poster for ToxCast Data Summit
Description:
Despite ever-increasing efforts in early safety assessment in all industries, there are still many chemicals that prove toxic in humans. While greater use of human in vitro test methods may serve to reduce this problem, the formal validation process applied to such tests represents a major hurdle to their adoption. We contend that what is really needed to justify the adoption of any new test is not a demonstration of an ability to identify all potential safety issues in one approach, but a clear demonstration that it is adding value or is superior to whatever is currently in use – ‘pragmatic validation’. A study based on such pragmatic validation, comparing the value of a range of human-based in vitro test methods with established regulatory tests, is currently underway. Importantly, all the in vitro tests have undergone significant evaluation already through two phases of the EPA ToxCast Program and are already used to various degrees by many pharmaceutical, agrichemical and cosmetic companies internally. The pragmatic validation approach we are testing now is designed to reduce to practice the application of these tests, bring them to a common denominator and provide the guidance to industry and regulators on the appropriate context of use. The study employs a range of marketed drugs that passed regulatory safety testing but were subsequently withdrawn, having caused serious toxicity in human subjects. Each of these drugs is paired with a negative control, i.e. a structurally and/or functionally similar marketed drug that does not exhibit such toxicity. This study is now being conducted as a distinct part of US EPA’s Phase 3 ToxCast in vitro profiling program. Data are to be made publicly available when testing is completed, at such time they will be submitted for detailed analysis to compare the performance of the new in vitro tests with the regulatory regime that secured the original marketing approval. On completion, the outcome of this unique study will be presented to the regulatory authorities with the aim of developing appropriate documents for use by the industry and published in peer-reviewed media. Preliminary data will be presented.
URLs/Downloads:
DOI: A Real-time Evaluation of Human-based Approaches to Safety Testing: What We Can Do Now (TDS)