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U.S. National Institutes of Health
Last Updated: 04/21/14

Toxicology and Pharmacology Branch (TPB)

Preclinical toxicology and pharmacology are required for decision making throughout drug discovery and development and for IND filing for clinical trials. Toxicological and pharmacological data can inform clinical trial design, such as determination of maximum tolerated dose, dose-limiting toxicities, and starting dose. With appropriate characterization, in most cases, safe operating parameters can be established for human clinical trials.

The Toxicology and Pharmacology Branch (TPB) of the Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute is the focus for obtaining and evaluating preclinical toxicology and pharmacology data on anti-cancer drugs and biologicals that have been approved for NCI discovery and development . The ultimate goal is to identify and characterize the toxicologic profile and pharmacokinetic properties of potential drug candidates and to support an Investigational New Agent Application (IND) or a Drug Master File (DMF) with the USFDA.

The TPB and it's predecessors have been involved in drug development of cancer drugs since 1955 when the Cancer National Service Center (CNSC) Program was created; in the development of AIDS Drugs since1986; cancer biologicals since 1992; cancer and to a more limited extent, AIDS vaccines since 1993; cancer gene therapy since 1995; and diagnostic imaging agents since 1996. A complete listing of INDs and or DMFs that the TPB has supported since 1986 is available.

The resources and expertise of the Toxicology and Pharmacology Branch can be applied to several steps in the drug discovery and development process.

Exploratory Screen Development Screening/Designed Synthesis Lead Development Candidate Seeking Clinical Candidate

Prepare project operational plan

Evaluate PK and PD using best available tools

Determine acute toxicity profile in vitro

Determine safety issues

Develop PD and toxicology biomarker assay(s)

Assess achievability of human PK/PD profile

Evaluate biopharmaceutical properties (absorption in rodents and non-rodents, clearance, and bioavailability)

Evaluate biodistribution

Evaluate clinical readiness of PK/PD
assay(s) and specimen handling SOPs

Evaluate safety issues (most sensitive species) in range-finding toxicology studies

Conduct IND-directed toxicology studies  including toxicokinetics

Determine preclinical MTD, DLTs, and clinical starting dose

Validate PK/PD assay(s) and specimen handling SOPs

Prepare and file IND