Radiobiology Research Suite Expansion of the TriMetis GLP Vivarium at UTHSC

UTHSC 的 TriMetis GLP Vivarium 放射生物学研究套件扩建

• 批准号: 10374310
• 负责人: GABOR J TIGYI
• 金额: $ 311.53万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374310
• 关键词: Accreditation; Animal Model; Animals; Biological Sciences; Chinese People; Clinical Trials; Dependence; Development; Drug Delivery Systems; Drug Kinetics; Evaluation; FDA approved; Health Sciences; Housing; Human; Industry; Laboratories; Lung; Macaca fascicularis; Macaca mulatta; Modeling; Pharmaceutical Preparations; Pharmacologic Substance; Preclinical Testing; Radiation; Radiation Injuries; Radiation Protection; Radiation Toxicity; Radiation therapy; Radiation-Sensitizing Agents; Radiobiology; Research; Research Contracts; Research Personnel; Resources; Rodent Model; Safety; Site; Sterility; Tennessee; Testing; Toxicology; United States National Aeronautics and Space Administration; United States National Institutes of Health; Universities; Withdrawal; animal facility; animal rule; cancer therapy; drug candidate; drug development; drug testing; foot; gastrointestinal; good laboratory practice; infrastructure development; irradiation; medical countermeasure; meetings; nonhuman primate; operation; pre-clinical research; programs; radiation countermeasure; radiation mitigator

There is no radiation medical countermeasure (RCM) drug approved by the FDA that meets the criterion of a gastrointestinal (GI) or lung radiomitigator – an agent that mitigates GI acute radiation syndrome (GI-ARS) or lung-ARS when administered after the exposure. A critical barrier to progress in development of RCM drugs is that a traditional human clinical trial is not an option. Therefore, FDA approval of a RCM is done under their Animal Rule (21 CFR 314.600) that requires detailed understanding of its mechanism of action, demonstration of safety and efficacy in animal models, including nonhuman primates (NHP), and its safety in humans. The recent withdrawal of Altasciences Corp., the only GI-ARS qualified contract research organization from RCM preclinical testing has created a critical shortage and a national strategic vulnerability in qualified drug development sites in the USA. Although the NIH, DOD, BARDA, NASA and several pharmaceutical companies are intensively pursuing RCM development projects there is no domestic test site currently available with an established and validated NHP models for the evaluation of RCM drug candidates, particularly for GI-ARS. This is compounded by the US dependence on foreign (PR Chinese) suppliers of rhesus macaques. The University of Tennessee Health Sciences Center (UTHSC) has a unique resource: the TriMetis Life Sciences Animal Facility (TAF). Since 2016, TAF has been operated and managed by UTHSC under its PHS Assurance and AAALAC accredited program. The TAF is a state-of-the-art vivarium housing small- and large-animals, including nonhuman primates, operated under FDA-approved Good Laboratory Practice (GLP), thereby meeting the needs of academic and industry researchers both regionally and nationally. The purpose of this proposal is to equip TAF with an radiation biology suite suitable for development of radiation countermeasure (RCM), radioprotective and radiosensitizer drugs under the Animal Rule. Installation of an irradiation suite at TAF will have a significant impact beyond the needs of RCM drug development: it will be optimal for the evaluation of radiotherapy sensitizers for cancer treatment, including general preclinical research, and drug testing with toxicology and pharmacokinetic studies. The UTHSC-owned Plough Center for Sterile Drug Delivery, where GMP manufacturing and compounding of test articles is done, the Regional Biocontainment Laboratory, where GLP radiation injury rodent models have already been in operation, are within a few hundred feet of the TAF and provide an unparalleled comprehensive drug development infrastructure that will meet all national academic and industry research and drug regulatory approval needs. The new state-of-the-art facility also develop domestically bred cynomolgus monkey radiation models thereby eliminating the US dependence on foreign suppliers.

FDA批准的放射医学对策（RCM）药物中没有一种符合 胃肠道（GI）或肺放射激动剂-一种缓解GI急性放射综合征（GI-ARS）的药物，或 暴露后给药时的肺-ARS。RCM药物开发进展的关键障碍 传统的人体临床试验是不可行的因此，FDA对RCM的批准是根据其 动物法规（21 CFR 314.600），要求详细了解其作用机制， 在动物模型（包括非人灵长类动物（NHP））中的安全性和有效性，以及在人体中的安全性。的 最近Altasciences公司的退出，唯一一家获得RCM GI-ARS资格的合同研究机构 临床前试验造成了合格药物的严重短缺和国家战略脆弱性， 在美国的发展基地。尽管美国国立卫生研究院、国防部、巴尔达、美国宇航局和几家制药公司 正在加紧进行RCM开发项目，目前没有国内试验场地， 建立并验证了NHP模型，用于评价RCM候选药物，特别是GI-ARS。 美国对外国（PR中国）恒河猴供应商的依赖加剧了这一点。的 田纳西大学健康科学中心（UTHSC）拥有独特的资源：TriMetis生命科学 动物设施（TAF）。自2016年以来，TAF一直由UTHSC在其PHS保证下运营和管理 AAALAC认证计划。TAF是一个最先进的动物园，饲养小型和大型动物， 包括非人灵长类动物，在FDA批准的良好实验室规范（GLP）下操作，从而满足 区域和国家学术和行业研究人员的需求。这项建议的目的 是为TAF配备适合制定辐射对策的辐射生物套件 (RCM)、放射防护和放射增敏剂药物。安装辐照室 在TAF将有一个显着的影响超出了RCM药物开发的需求：它将是最佳的 评价用于癌症治疗的放射治疗增敏剂，包括一般临床前研究和药物 通过毒理学和药代动力学研究进行测试。UTHSC拥有的无菌药物输送中心， 在进行GMP生产和供试品混合的地方，区域生物防护实验室， GLP辐射损伤啮齿动物模型已经在运行，在几百英尺的范围内， TAF提供了无与伦比的全面药物开发基础设施，将满足所有国家 学术和行业研究以及药品监管部门的批准需求。新的最先进的设施还 开发国内饲养的食蟹猴辐射模型，从而消除对美国的依赖 外国供应商。