Animal Efficacy and Pharmacometric Modeling Core

动物功效和药理学建模核心

• 批准号: 10194366
• 负责人: Isabel Lauren Jackson
• 金额: $ 99.49万
• 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/10194366
• 关键词: Acute; Advanced Development; Animal Model; Animals; Biological; Biological Markers; Blinded; Blood; Blood specimen; Bone Marrow; Chemistry; Chinese People; 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