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.

目前还没有 FDA 批准的符合放射医学对抗（RCM）标准的放射医学对抗（RCM）药物 胃肠道 (GI) 或肺部放射缓解剂 – 缓解胃肠道急性放射综合征 (GI-ARS) 或 暴露后施用肺-ARS。 RCM 药物开发进展的关键障碍 传统的人体临床试验不是一种选择。因此，FDA 对 RCM 的批准是根据其规定进行的 动物规则 (21 CFR 314.600)，需要详细了解其作用机制、演示 动物模型（包括非人类灵长类动物（NHP））的安全性和有效性及其对人类的安全性。这 最近，唯一一家具有 GI-ARS 资格的合同研究机构 Altasciences Corp. 从 RCM 中退出 临床前试验造成合格药品严重短缺和国家战略脆弱性 美国的开发地点。尽管 NIH、DOD、BARDA、NASA 和多家制药公司 正在大力开展 RCM 开发项目，目前国内尚无具备 建立并验证了 NHP 模型，用于评估 RCM 候选药物，特别是 GI-ARS。 美国对外国（中国）恒河猴供应商的依赖使情况更加复杂。这 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 保障下运营和管理 和 AAALAC 认证计划。 TAF 是一个最先进的动物园，饲养着小型和大型动物， 包括非人类灵长类动物，根据 FDA 批准的良好实验室规范 (GLP) 进行操作，从而满足 地区和国家学术和行业研究人员的需求。本提案的目的 为TAF配备适合开发辐射对抗措施的辐射生物学套件 (RCM)、动物规则下的放射防护和放射增敏药物。安装辐照套件 TAF 将产生超出 RCM 药物开发需求的重大影响：这将是最佳选择 癌症治疗放疗增敏剂的评估，包括一般临床前研究和药物 毒理学和药代动力学研究测试。 UTHSC 拥有的 Plough 无菌药物输送中心， 区域生物防护实验室是进行 GMP 生产和测试物品配制的地方， GLP 辐射损伤啮齿动物模型已经投入使用，距离辐射源几百英尺。 TAF 并提供无与伦比的综合药物开发基础设施，以满足所有国家的需求 学术和行业研究以及药物监管审批需求。新的最先进的设施还 开发国产食蟹猴辐射模型，从而消除对美国的依赖 关于国外供应商。