Radiobiology Research Suite Expansion of the TriMetis GLP Vivarium at UTHSC

FDA批准的放射医学对策(RCM)药物没有符合 胃肠道(GI)或肺放射增强剂-一种减轻GI急性辐射综合征(GI-ARS)或 肺-ARS，在暴露后给药。制约RCM药物发展的关键障碍 传统的人体临床试验不是一种选择。因此，FDA对RCM的批准是根据其 动物规则(21 CFR 314.600)，要求详细了解其作用机制、演示 在包括非人类灵长类动物(NHP)在内的动物模型中的安全性和有效性，以及在人类中的安全性。这个 最近，唯一符合GI-ARS资格的合同研究机构Altasciences Corp.从RCM退出 临床前试验在合格药物方面造成了严重短缺和国家战略漏洞 在美国的开发地点。尽管NIH、国防部、BARDA、NASA和几家制药公司 正在紧锣密鼓地进行RCM开发项目，目前国内还没有可用的试验场 建立并验证了用于评价RCM候选药物，特别是GI-ARS的NHP模型。 美国对外国(公关中国)猕猴供应商的依赖更是雪上加霜。这个 田纳西大学健康科学中心(UTHSC)有一个独特的资源：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 和AAALAC认可的项目。TAF是一种最先进的隔膜，容纳了小动物和大动物， 包括非人类灵长类动物，在FDA批准的良好实验室操作规范(GLP)下操作，从而满足 满足地区和国家的学术和行业研究人员的需求。这项建议的目的是 是为TAF配备一套适合于开发辐射对抗的辐射生物学套件 (RCM)、辐射防护和辐射增敏药物。安装一套辐照设备 At TAF将产生超出RCM药物开发需求的重大影响：它将是 放射增敏剂用于癌症治疗的评价，包括一般临床前研究和药物 毒理学和药代动力学研究的检测。UTHSC旗下的普劳无菌药物输送中心， 在进行GMP制造和测试物品合成的地方，区域生物遏制实验室， GLP辐射损伤啮齿动物模型已经投入使用的地方，距离 并提供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审批的需要。新的最先进的设施还 建立国产食蟹猴辐射模型，从而消除对美国的依赖 关于外国供应商。

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.