Animal Efficacy and Pharmacometric Modeling Core

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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.