Animal Efficacy and Pharmacometric Modeling Core

动物功效和药理学建模核心

• 批准号: 10401458
• 负责人: Isabel Lauren Jackson
• 金额: $ 79万
• 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/10401458
• 关键词: Acute; Advanced Development; Animal Model; Animals; Biological Markers; Biological Products; Blinded; Blood; Blood specimen; Bone Marrow; Chemistry; Chinese; Coagulation Process; Collaborations; Controlled Study; Cutaneous; Data; Development; Doctor of Philosophy; Dose; Drug Kinetics; Ensure; Ethics; Fibroblast Growth Factor; Future; Hematology; Human; Investigational New Drug Application; Laboratories; Macaca mulatta; Marketing; Maryland; Miniature Swine; Modeling; Monitor; National Institute of Allergy and Infectious Disease; Nuclear; Nuclear Accidents; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Radiation Accidents; Radiation Injuries; Radiation Sicknesses; Radiation Syndromes; Radiation exposure; Radiology Specialty; Randomized; Regimen; Regulation; Regulatory Affairs; Regulatory Pathway; Resources; Rodent; Safety; Secure; Serum; Services; Skin; Standardization; System; Technology; Testing; Therapeutic; Thromboplastin; Tissue Banks; Tissue Sample; Toxic effect; Treatment Protocols; United States Food and Drug Administration; United States National Institutes of Health; Validation; Whole-Body Irradiation; animal efficacy; animal rule; archive data; assay development; biodosimetry; biomarker identification; data archive; data framework; data integrity; data standards; database query; drug development; efficacy evaluation; efficacy study; experience; flexibility; good laboratory practice; irradiation; medical countermeasure; member; mid-career faculty; models and simulation; nanoparticle; nonhuman primate; pharmacokinetics and pharmacodynamics; pharmacometrics; porcine model; preclinical trial; quality assurance; radiation countermeasure; screening; stem; translational medicine; trial design

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 多物种功效和药理学建模核心的目标是作为一个联盟- 广泛的资源，以帮助开发用于治疗ARS和/或DEARE的MCM。核心B完成 通过提供一套全面而灵活的服务， 针对试验性新药（IND）申请的医学对策（MCM），以缓解和/或 治疗急性放射病（ARS）和急性辐射照射的延迟效应（DEARE） 辐射或核事故的受害者。核心B具有进行安全性、药理学和MCM的能力 在兔、小型猪和非人灵长类动物（NHP）全身和部分照射模型中的有效性研究。的 核心由伊莎贝尔L博士领导。杰克逊是一位副教授，他在啮齿动物、兔子、 小型猪，ARS/DEARE和MCM筛选的NHP模型，以及Joga Gobburu博士，博士，MBA，他带来了一个 广泛的转化医学背景，源于他的实践药物经验的项目 发展和监管事务。核心有内部能力监测血液和血清 化学参数，进行常规凝血和组织因子测试，并提供分析支持 生物标志物鉴定、物种特异性测定开发和鉴定以及验证服务。到 确保所生成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药物非临床研究质量管理规范规定的质量管理体系， 独立质量保证部门（QAU）监督，如21 CFR 58.35所述。专业知识在先进 临床前试验设计以及统计学和药代动力学（PK）支持，包括药理学建模 并且可以进行剂量/方案选择和对人的剂量缩放的模拟。最后，核心B将 建立一个标准化的数据存档框架和一个血液和组织储存库，以与NIH的 与协调中心核心合作，实现动物减少、改良和替代的3R。 来自假照射和全身或部分身体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联盟用于推进新目标识别、医疗对策 发现和发展，以及生物剂量测定技术。