BIOLOGICAL TESTING FACILITY-CONTRACEPTIVE PRECLINICAL DEVELOPMENT

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Within NICHD/DIPHR, the Contraceptive Development Program (CDP) supports research to develop compounds that can disrupt normal ovulation, sperm production or sperm function for the purpose of developing safe, effective and affordable contraceptives for men or women. The Biological Testing Facility (BTF) is designed to permit rapid evaluation of new compositions-of­ matter, drug formulations, delivery systems, and devices for contraceptive and endocrine activity. The BTF provides overall project management and the capabilities to support all phases of preclinical activities pursuant to development of new contraceptive methods: these include, but are not limited to in vitro and in vivo assays, plasma and microsomal stability studies, absorption, distribution, metabolism, excretion and toxicity (ADMET), pharmacokinetic (PK) and pharmacodynamic (PD) profiling, animal activities and studies, manufacture of active pharmaceutical ingredients (APis), process and product development, formulation, clinical lot production, preclinical enabling studies and associated tasks leading to the filing of investigational new drug (IND) applications. Compounds formulated by the BTF are prepared under current Good Manufacturing Practices (cGMP) to allow clinical evaluation in the CDP Contraceptive Clinical Trials Network (CCTN). The CCTN investigators have develop protocols to evaluate the drug candidates identified as high priority by the Program. The BTF has been working with the CORs for the Chemical Synthesis Facility and the CCTN and with the investigators in the CCTN to develop and test the appropriate formulations for clinical batches of the candidate compounds. The next clinical study for each candidate drug is dependent on timely receipt of clinical batches to begin the process of recruitment and emollment. Drugs that are currently in ongoing clinical trials require stability testing of the clinical formulations. The Biological Testing Facility plays a critical role in the drug development mission of the CDP. Scope and Objectives: Contraceptive preclinical discovery and development activities using in house or appropriate subcontract facilities as described in the Background including but not limited to discovery and optimization of APis, in vivo and in vitro assays, efficacy, safety and toxicology of new chemical entities (NCEs) and/or active pharmaceutical ingredients (API) in appropriate formulation and appropriate concentrations that will be suitable for use in clinical trials of a potential contraceptive products will be supported by this task. The task requires that the contractor provide documentation and reports of studies to support regulatory filings acceptable to stringent regulatory agencies. The contraceptive agents manufactured under cGMP may be administered as oral, implant, injectable, transdermal, intravaginal and intrauterine formulation or other routes of delivery/administration of therapeutic agents that are acceptable for clinical materials and for clinical trials. The formulated drug products shall be characterized for in vivo safety and toxicology studies and GLP studies when appropriate in all areas and species. These studies would determine the route of administration and duration of activity pursuant to filing an IND that would support testing in clinical trials and ultimately toward filing a New Drug Application (NDA) for approval of a new method.