BIOLOGICAL TESTING FACILITY - CHARACTERIZATION OF POTENTIAL OVULATION INHIBITORS

背景资料： 国家儿童健康与发展研究所的避孕研究分支（CRB）支持研究开发能够破坏正常排卵、精子生成或精子功能的化合物，以便为男性或女性开发安全有效的避孕药具。生物试验设施（BTF）的目的是允许快速评估新的物质组合物，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（ADME）、毒性、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。BTF有能力根据现行药品生产质量管理规范（cGMP）制备化合物，以进行临床评价。BTF一直在与化学合成设施和避孕临床试验网络的订约官员代表以及避孕临床试验网络的调查人员合作，开发和测试候选化合物临床批次的适当配方。BTF在CRB的药物开发使命中发挥着关键作用。 范围和目标： 如背景技术中所述，使用内部或适当的实验室设施进行的潜在避孕产品的临床前活动包括但不限于以下内容： 1)化合物的表征，包括化学结构的确认和适用于体外和体内研究的适当制剂的开发。2)通过体内和体外试验对化合物和/或活性药物成分（API）进行生物学测试，以测量微粒体稳定性、PK、PD、ADME、在适当的媒介物和适当的化合物浓度中的功效、安全性和毒理学。这些研究将支持化合物的早期表征，这些化合物将支持临床试验中的最终测试，并最终提交新药申请（NDA）以批准一种新的避孕方法。

Background: The Contraception Research Branch (CRB) within NICHD supports research to develop compounds that can disrupt normal ovulation, sperm production or sperm function so that safe and effective contraceptives can be developed 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 (ADME), toxicity, 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. The BTF has the capability to prepare compounds under current Good Manufacturing Practices (cGMP) to allow clinical evaluation. The BTF has been working with the Contracting Officer’s Representatives (CORs) for the Chemical Synthesis Facility and the Contraceptive Clinical Trials Network (CCTN) and with the investigators in the CCTN to develop and test the appropriate formulations for clinical batches of the candidate compounds. The BTF plays a critical role in the drug development mission of the CRB. Scope and Objectives: Preclinical activities of potential contraceptive products using either in-house or appropriate subcontract facilities as described in the Background including but not limited to the following: 1)Characterization of compounds including confirmation of chemical structure and development of appropriateformulations suitable for in vitro and in vivo studies. 2) Biologic testing of compounds and/or active pharmaceutical ingredients (API) by in vivo and in vitro assays to measure microsome stability, PK, PD, ADME, efficacy, safety and toxicology in appropriate vehicles and appropriate compound concentrations. These studies would support early characterization of compounds that would support eventual testing in clinical trials and ultimately toward filing a New Drug Application (NDA) for approval of a new method of achieving contraception.