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Home Ames Test Mouse Lymphoma Assay Chromosome Aberration Test Micronucleus Test Rat Liver UDS Test Comet Assay ICH and FDA recommendations Links |
Introduction to ICH and FDA Recommendations Short term tests are usually performed at an early stage of compound development. They are needed to predict genotoxic effects, which could potentially have a wide range of serious consequences. The US FDA and most other important regulatory bodies concerned with registration of potential new drugs that have adopted the recommendations of the ICH relating to genotoxicity testing. A standard test battery onsists of two in vitro tests performed prior to initiation of phase 1 clinical trials and an in vivo rodent test for chromosome damage performed prior to phase 2 clinical trials.In vitro The bacterial mutation test (Ames test) is required for all new drugs. Modifications to the test may be required depending on the physical and chemical nature of the test article, for instance, special methods for volatile substance and for certain chemical classes. Chromosome aberration tests can be performed using primary human lymphocyte cultures allow more confidence in the results obtained than those using immortal cell lines. The mammalian cell mutation test is an equally acceptable alternative to the chromosome aberration test. Various assays are avaialable, but the only version that is acceptable to ICH is looking for aberrations of the thymidine kinase gene of L5178Y cells. This assay is sensitive to both gene mutations and chromosome aberrations. In vivo The rodent erythrocyte micronucleus test and the rodent bone marrow chromosome aberration test are equally acceptable alternative tests. In practice, the micronucleaus test is nearly always preferred because it is sensitive to a wider range of genotoxic agents, it has a better statistical basis and is less expensive. Where there are special concerns, the rodent liver UDS test may occasionally be used to support the micronucleus test.
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