BIOLOGICAL TESTING FACILITY - CHARACTERIZATION OF POTENTIAL OVULATION INHIBITORS

背景： NICHD内的避孕研究处(CRB)支持研究开发可能扰乱正常排卵、精子产生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。生物测试设施(BTF)旨在允许对新的物质成分、药物配方、给药系统和避孕和内分泌活动装置进行快速评估。BTF根据新避孕方法的开发提供全面的项目管理和能力，以支持临床前活动的所有阶段，这些方法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)的制造、工艺和产品开发、配方、临床批量生产、临床前使能研究和导致提交研究性新药(IND)申请的相关任务。BTF有能力根据当前的良好制造规范(CGMP)制备化合物，以便进行临床评估。BTF一直在与化学合成设施和避孕临床试验网络(CCTN)的合同官员代表(CORS)以及CCTN的研究人员合作，为候选化合物的临床批次开发和测试适当的配方。BTF在CRB的药物开发任务中发挥着关键作用。 范围和目标： 潜在避孕产品的临床前活动，使用内部或背景中描述的适当分包设施，包括但不限于以下内容： 1)化合物的表征，包括确认化学结构和开发适合于体外和体内研究的适当剂型。2)通过体内和体外试验对化合物和/或活性药物成分(API)进行生物测试，以测量微生物体的稳定性、PK、PD、ADME、在合适的载体和适当的化合物浓度下的有效性、安全性和毒理学。这些研究将支持化合物的早期表征，这些化合物将支持最终在临床试验中进行测试，并最终提交新药申请(NDA)，以批准一种实现避孕的新方法。

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.