BIOLOGICAL TESTING FACILITY-CONTRACEPTIVE PRECLINICAL DEVELOPMENT

在NICHD/DIPHR内，避孕药具开发方案支持研究开发能够破坏正常排卵、精子生产或精子功能的化合物，目的是为男性或女性开发安全、有效和负担得起的避孕药具。生物试验设备（BTF）的设计目的是允许快速评价新的合成物，药物配方，输送系统，以及避孕和内分泌活动的装置。BTF提供全面的项目管理和能力，以支持根据新避孕方法开发的临床前活动的所有阶段：这些包括但不限于体外和体内分析，血浆和微粒体稳定性研究，吸收、分布、代谢、排泄和毒性（ADMET），药代动力学（PK）和药效学（PD）分析，动物活动和研究，活性药物成分（API）的生产、工艺和产品开发、配方、临床批量生产、临床前使能研究以及导致提交研究性新药（IND）申请的相关任务。由BTF配制的化合物根据现行药品生产质量管理规范（cGMP）制备，以便在CDP避孕临床试验网络（CCTN）中进行临床评价。CCTN研究人员已经制定了方案，以评估该计划确定为高优先级的候选药物。BTF一直在与化学合成机构和CCTN的COR以及CCTN的研究人员合作，开发和测试候选化合物临床批次的适当配方。每种候选药物的下一项临床研究取决于是否及时收到临床批次，以开始招募和给药过程。目前正在进行临床试验的药物需要进行临床制剂的稳定性试验。生物试验机构在CDP的药物开发使命中发挥着关键作用。 范围和目标： 使用如背景技术中所述的内部或适当的实验室设施的避孕药临床前发现和开发活动，包括但不限于API的发现和优化、体内和体外测定、功效，新化学实体（NCE）和/或活性药物成分（API）的安全性和毒理学在适当的配方和适当的浓度，将适合用于临床试验的潜在避孕产品将支持这项任务。这项任务要求承包商提供文件和研究报告，以支持严格的监管机构可接受的监管文件。在cGMP下制造的避孕剂可以作为口服、植入、注射、透皮、阴道内和子宫内制剂或其他给药途径施用。 递送/施用对于临床材料和临床试验可接受的治疗剂。应在所有区域和种属中对配制制剂进行体内安全性和毒理学研究以及GLP研究（如适用）。这些研究将根据提交IND确定给药途径和活性持续时间，以支持临床试验中的测试，并最终提交新药申请（NDA）以批准新方法。

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.