The T&PB plans, directs and evaluates a collaborative, extramural, contract-supported program in anti-cancer and anti-AIDS drug and vaccine development to:
- Develop methodologies to determine levels of drugs and/or their metabolites in biological matrices.
- Determine the pharmacokinetic profile of drugs of interest in various species.
- Integrate pharmacological data into the drug development process in order to minimize undesirable toxicity and to attain effective drug levels.
- Determine the toxicological effect of new and established anti-tumor and antiviral agents and modalities on experimental animals.
- Guide the development of special target organ toxicity assays.
- Provide assistance to other units in the evaluation of the toxicity of biological agents and experimental formulations.
- Evaluate the toxicity and safety of potential new vaccines for use in the immunization against cancer and AIDS.
- Determine the biochemical mechanism of action of high priority anti-tumor agents.
- Conduct regular surveillance of the literature for new developments in the fields of toxicologic and pharmacologic evaluation which may be applicable to the needs of the Institute.
- Summarize all pharmacology and toxicology data for the Division's Drug Development Committee and make recommendations as to target organ toxicity and safe starting doses for Phase I clinical trials.
- Provide the pharmacological and toxicological input and assessments needed for the preparation of Investigational New Drug Applications (IND) and Drug Master Files (DMF).
- Interact with other programs to provide information on preclinical pharmacology and toxicology data which is used in formulating recommendations for doses, dose escalation schemes and treatment schedules for clinical trial.
The primary responsibility of the T&PB then is to obtain the toxicology and pharmacology data that are necessary for the NCI to file an Investigational New Drug Application (IND) with the FDA in order to conduct Phase I clinical trials of new chemotherapeutic agents in man. The T&PB goes about fulfilling its mission in a number of ways.
Once a potential agent is identified for development by the DCTD Drug Development or RAID Committees, the T&PB, using the procedures outlined in another section of this document develops a tentative plan to evaluate the agent and then assigns it to one or more pharmacology and/or toxicology contractors as necessary to perform the required studies. As studies progress and results become available, the development plan is modified as necessary until the IND-directed toxicology studies that will support the clinical protocol are designed and completed.
Go to T&PB Drug Development Process and Procedures
Throughout this process, the T&PB interacts with the drug supplier and any other groups that are involved in the development process through participation in DTP Operating Committees (DDG and RAID), DCTD Drug Working Groups (DDG and RAID) and the DCTD Drug Development Group. In this manner, everyone involved in the development process is made aware of the results of on-going studies and the development plan can be modified to take into account the most recent data with regard to the best drug candidate for development, the most reasonable drug formulation, and the optimal route and schedule of administration.
Studies are assigned to the T&PB contractor with the most appropriate experience in either evaluating a particular type of agent or in performing specific types of studies. Collaborative arrangements are created between various T&PB contractors and other groups within the NCI, NIH, and drug suppliers to permit the development to proceed in the most facile and expeditious manner. Development by T&PB can take many forms ranging from those drugs that the T&PB develops in their entirety with no outside assistance to those for which the T&PB serves as a consultant to design, monitor and/or evaluate studies performed by drug suppliers. Once the histopathology results become available from the various toxicity studies, the T&PB has these results peer reviewed by a board-certified pathologist from the T&PB pathology and veterinary support contractor to make certain that no drug-related lesions have been missed or inappropriately labeled as such and that diagnoses are consistent across studies and species.