Animal Efficacy and Pharmacometric Modeling Core

动物功效和药理学建模核心

基本信息

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
项目类别：
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

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

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项目摘要

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.

抽象的多物种效率和药物建模核心的目的是作为财团广泛的资源，以帮助开发MCM，以治疗ARS和/或Deare。核心B成就通过提供一套全面而灵活的服务来实现这一目标医学对策（MCM）针对调查新药（IND）缓解和/或治疗急性辐射病（ARS）和急性辐射暴露的延迟影响（Deare）令人惊讶的是，进行安全性，药理学和MCM的能力兔子，米蒂皮格和非人类灵长类动物（NHP）模型的疗效研究。这 Core由伊莎贝尔·L·杰克逊（Isabel L. Jackson）博士领导，他是啮齿动物，兔子的发展专家的副教授， Minipig和ARS/Deare和MCM Searing的NHP模型以及MBA博士Joga Gobburu博士转化医学的广泛背景是源于他动手药物的经验而引起的项目发展和监管事务。核心具有监测血液学和串行的内部功能化学参数，进行常规加密和组织因子测试，并提供分析支持用于生物标记识别的服务，规格特定的评估开发和资格以及验证。到确保生成的数据的质量和完整性，核心B下的所有研究都可以合规进行凭借质量管理系统符合FDA的良好实验室实践法规 21 CFR 58.35中概述的独立质量保证单位（QAU）监督。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，包括药技术建模以及对人类的剂量/方案选择和剂量缩放的模拟。最后，核心B将建立一个标准化的框架，用于数据存档和血液和组织存储库，以与NIH保持一致 3 R与协调中心核心合作减少动物，精致和替换。从假辐照和全部或部分辐照动物的组织和血液样本的可用性可能是由更广泛的CMCR联盟使用来推进新的目标识别，医疗对策发现与发展以及生物测量技术。