SYNTHESIS OF BULK CHEMICALS & DRUGS FOR PRECLINICAL USE

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The Pharmaceuticals Resources Branch (PRB) of the Developmental Therapeutics Program (DTP) of the Division of Cancer Treatment, Diagnosis and Chemotherapy (DCTDC) of the National Cancer Institute has primary responsibility for the production of a variety of compounds as bulk pharmaceuticals for use in both clinical and preclinical evaluations as potential anti-AIDS agents and anticancer agents. The PRB works closely with the DTP screening group to prepare larger quantities of drug candidates for in vivo evaluation and for the preparation of derivatives of drug candidates with improved physical properties, such as improved solubility or better pharmacokinetic properties, through the use of pro-drugs or other selected chemical derivatives. As part of this process, the PRB may undertake the development of existing or new, more efficient, chemical processes, procedures, and techniques for the preparation of those compounds of interest. Once identified as a potential drug candidate for anti-AIDS or anticancer treatment, the PRB undertakes the scale-up preparation of varying amounts of compound, based on the immediate needs of the program. The amounts may range from milligram quantities to multi-kilogram quantities, depending upon the stage of development of the compound and its biological potency. Once accepted for human clinical trials, the PRB is responsible for the preparation of clinical materials that meet the FDA requirements for Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) drug production. As such the procedures developed by PRB will define the purity standards and criteria for the clinical bulk pharmaceutical based on those produced during the scale-up process. The purpose of this project is to obtain contractors who have the equipment and expertise to conduct organic synthesis and purification of potential anti-AIDS and anticancer drug candidates in quantities up to multi-kilogram amounts. Further, they must be capable of production under GMP and GLP conditions when needed. They will be called upon to procure, purity (if necessary) and characterize substances from suitable sources; perform preliminary stability, solubility, and analytical studies on the products; and prepare analytical reference standards, and novel derivatives as needed by the program.