The objective of this contract is to acquire pharmacologic and toxicologic data on new drug candidates for the treatment of cancer and other diseases, including orphan diseases. Cancer imaging agents with the potential for diagnosing and monitoring tumor progression are evaluated using this contract as well. These data are routinely submitted to the FDA as part of an investigational new drug (IND) application and as such will conform with all FDA Guidances. The work scope for this contract includes: a) Validation of analytical procedures for dose concentration analyses and for assaying drug candidate concentrations in biological fluids. b) Conduct pharmacokinetic studies in rodent and non-rodent species to determine plasma elimination kinetics. Determine bioavailability of non-parenteral routes and plasma clearance rates in order to establish the dose required to produce effective concentrations in plasma and apply the information to design drug candidate-specific toxicology studies. c) Conduct preliminary toxicology studies to establish relative toxicity of the drug candidate in rodent and non-rodent species and potential dose limiting toxicities. d) Conduct definitive toxicology studies to establish toxicity and safety in relation to drug candidate exposure (plasma concentration or area under the drug concentration versus time curve). These studies are performed in rodent and non-rodent species, as required by the FDA. Studies are customized for the drug candidate being evaluated, such as specifying the route and schedule of administration and include general toxicity/safety determinations, but may include specialized evaluations such as cardiovascular toxicity, neurotoxicity, immunotoxicity, pulmonary toxicity, or reproductive/teratology effects. e) Conduct in vitro studies such as mutagenicity and bone marrow assays.
