Flow Cytometry in Preclinical Toxicology/safety Assessment

The primary departmental goal of preclinical toxicology (a.k.a. safety assessment) in drug development is to identify and characterize drug-induced toxicity in test animals by using appropriate animal models. This is accomplished through a large number of individual studies, sometimes referred to as a “tox package,” designed to provide specific data on the pharmacology/toxicology of the drug candidate including determination of acute, subacute, and chronic toxicity, carcinogenicity, mutagenicity, teratogenicity, and effects on the reproductive system. Various study designs are employed. Dose ranging and/or dose escalating studies are typically completed early in the safety assessment phase of drug development. This study design is meant to provide maximum tolerated dose (MTD) and no observable (adverse) effect level (NOEL orNOAEL), two important pieces of information that aid in selection of doses for repeat dosing and/or chronic studies. Acute, single-dose experimental designs are also used early in the safety phase to identify organs/tissues that are targets of toxicity. After toxicity is identified, it is important to determine if the effect is reversible given that the animal is allowed to recover for a period of time after administration of the last dose. Reversibility studies may be done separately or a recovery group may be included in a particular study design. It is possible to use varying routes of administration across studies, but it is critical to sufficiently investigate the route intended