BIOLOGICAL TESTING FACILITY - CHARACTERIZATION OF POTENTIAL OVULATION INHIBITORS

生物测试设施 - 潜在排卵抑制剂的表征

• 批准号: 10021077
• 负责人: TOUFAN PARMAN
• 金额: $ 75万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-27 至 2020-09-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021077
• 关键词: Animals; Biological Assay; Biological Testing; Chemical Structure; Clinical; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive Devices; Contraceptive methods; Contracts; Development; Drug Formulations; Drug Kinetics; Endocrine; Evaluation; Excretory function; Formulation; In Vitro; Investigational New Drug Application; Measures; Metabolism; Methods; Microsomes; Mission; National Institute of Child Health and Human Development; Ovulation; Pharmacodynamics; Pharmacologic Substance; Phase; Plasma; Play; Process; Production; Research; Research Personnel; Research Support; Role; Safety; System; Testing; Toxic effect; Toxicology; Woman; absorption; chemical synthesis; clinical lot; design; drug development; in vitro Assay; in vivo; inhibitor/antagonist; lot production; men; novel therapeutics; pharmacokinetics and pharmacodynamics; pre-clinical; product development; research clinical testing; sperm cell; sperm function

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.

背景： NICHD 的避孕研究部门 (CRB) 支持研究开发可以扰乱正常排卵、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。生物测试设施 (BTF) 旨在快速评估新的物质成分、药物配方、输送系统以及避孕和内分泌活性装置。 BTF 提供整体项目管理和支持新避孕方法开发的临床前活动所有阶段的能力：这些包括但不限于体外和体内测定、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 (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 有能力根据现行良好生产规范 (cGMP) 制备化合物以进行临床评估。 BTF 一直与化学合成设施和避孕临床试验网络 (CCTN) 的合同官员代表 (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。 BTF 在 CRB 的药物开发任务中发挥着关键作用。 范围和目标： 使用背景中所述的内部或适当的分包设施进行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合体外和体内研究的适当制剂的开发。 2) 通过体内和体外测定对化合物和/或活性药物成分（API）进行生物学测试，以在适当的载体和适当的化合物浓度下测量微粒体稳定性、PK、PD、ADME、功效、安全性和毒理学。这些研究将支持化合物的早期表征，从而支持临床试验中的最终测试，并最终提交新药申请（NDA）以批准实现避孕的新方法。