Animal Efficacy and Pharmacometric Modeling Core

动物功效和药理学建模核心

• 批准号: 10845825
• 负责人: Isabel Lauren Jackson
• 金额: $ 137.06万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-16 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10845825
• 关键词: Animal; Efficacy; Pharmacometric; Modeling; Core

ABSTRACT The objective of the multispecies efficacy and pharmacometric modeling core is to serve as a consortium-wide resource to aid in the development of MCMs for the treatment of ARS and/or DEARE. Core B accomplishes this objective through the provision of a comprehensive and flexible set of services to bring new and repurposed medical countermeasures (MCM) towards Investigational New Drug (IND) application for the mitigation and/or treatment of acute radiation sickness (ARS) and the delayed effects of acute radiation exposure (DEARE) in victims of radiological or nuclear incidents. Core B has the capability to conduct safety, pharmacology, and MCM efficacy studies in rabbit, minipig, and non-human primate (NHP) models of total and partial body irradiation. The Core is led by Dr. Isabel L. Jackson, an associate professor with expertise in the development of rodent, rabbit, minipig, and NHP models of ARS/DEARE and MCM screening and Dr. Joga Gobburu, PhD, MBA who brings a broad background in translational medicine to the projects stemming from his experience with hands-on drug development, and regulatory affairs. The Core has in-house capabilities to monitor hematological and serum chemistry parameters, conduct routine-coagulation and tissue factor tests, and provide analytical support services for biomarker identification, species-specific assay development and qualification, and validation. To ensure the quality and integrity of the data generated, all studies under Core B can be conducted in compliance with a quality management system that complies with the FDA’s Good Laboratory Practice regulations with independent Quality Assurance Unit (QAU) oversight as outlined in 21 CFR 58.35. Expertise in advanced preclinical trial design and statistical and pharmacokinetics (PK) support, including pharmacometric modeling and simulation for dose/regimen selection and dose-scaling to humans are available. Finally, Core B will establish a standardized framework for data archiving and a blood and tissue repository to align with the NIH’s 3 R’s for animal reduction, refinement, and replacement in collaboration with the coordinating center core. Availability of tissue and blood samples from sham-irradiated and total or partial body irradiated animals may be utilized by the broader CMCR consortium to advance new target identification, medical countermeasure discovery and development, and biodosimetry technologies.

摘要 多物种功效和药物计量模拟核心的目标是作为联盟范围内的资源，帮助开发用于治疗ARS和/或DeARE的MCM。核心B完成 这一目标通过提供一套全面而灵活的服务来带来新的和重新调整的用途 针对新药申请缓解和/或影响的医学对策(MCM) 急性放射病(ARS)的治疗和急性辐射暴露(DEARE)的延迟效应 辐射或核事故的受害者。核心B有能力进行安全、药理学和MCM 兔、小型猪和非人灵长类动物(Nhp)全身和部分照射模型的疗效研究。这个 CORE由伊莎贝尔·L·杰克逊博士领导，他是一位副教授，擅长发展啮齿动物、兔子和 和NHP模型的ARS/Deare和MCM筛查，以及Joga Gobburu博士，博士，MBA，他带来了 他在转化医学方面的广泛背景来自于他实践药物的经验 发展和监管事务。Core具有内部监控血液学和血清的能力 化学参数，进行常规凝血和组织因子检测，并提供分析支持 生物标记物识别、特定物种化验开发和鉴定以及验证的服务。至 确保生成的数据的质量和完整性，核心B项下的所有研究均可合规进行 具有符合FDA的良好实验室操作规范的质量管理体系 独立的质量保证单位(QAU)监督，如21 CFR 58.35所述。高级专业知识 临床前试验设计以及统计和药代动力学(PK)支持，包括药物计量建模 对人体的剂量/方案选择和剂量比例的模拟是可用的。最后，核心B将 建立标准化的数据存档框架和血液和组织储存库，以与NIH的 与协调中心核心协作，用于动物减少、改进和替换的3个R。 来自假照射和全身或部分照射动物的组织和血液样本的可用性可能是 被更广泛的CMCR财团用来推进新的目标识别、医学对策 发现和发展，以及生物剂量学技术。