Genetic toxicity assessment: employing the best science for human safety evaluation. Part I: Early screening for potential human mutagens.
Results of genetic toxicology tests are used by FDA's Center for Drug Evaluation and Research as a surrogate for carcinogenicity data during the drug development process. Mammalian in vitro assays have a high frequency of positive results which can impede or derail the drug development process. To reduce the risk of such delays, most pharmaceutical companies conduct early non-GLP (good laboratory practices) studies to eliminate drug candidate with mutagenic or clastogenic activity. Early screens include in silico structure activity assessments and various iterations of the ultimate regulatory mandated GLP studies.
Jacobson-Kram
David
D
Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA. david.jacobsonkram@fda.hhs.gov
Contrera
Joseph F
JF
D000818:Animals; D001681:Biological Assay / Q000379:methods; D002460:Cell Line; D002869:Chromosome Aberrations / Q000187:drug effects; D003198:Computer Simulation; D004269:DNA, Bacterial / Q000187:drug effects; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D023281:Genomics / Q000379:methods; D017408:Guidelines as Topic; D006801:Humans; D008956:Models, Chemical; D009152:Mutagenicity Tests / Q000379:methods* / Q000592:standards; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009154:Mutation; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D018570:Risk Assessment; D014481:United States; D014486:United States Food and Drug Administration
D004269:DNA, Bacterial; D009153:Mutagens