Enabling nationwide AD PET imaging to support most efficient clinical trials by adoption of radically simplified and standardized quality control in commercial production of AD PET tracers.

通过在 AD PET 示踪剂的商业生产中采用彻底简化和标准化的质量控制，使全国范围内的 AD PET 成像能够支持最有效的临床试验。

• 批准号: 10156578
• 负责人: Arkadij Elizarov
• 金额: $ 125.63万
• 依托单位: TRACE-ABILITY, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10156578
• 关键词: Achievement; Adoption; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease therapy; Amyloid; Amyloid beta-Protein; Automation; Back; Biological Markers; Brain; Brain Pathology; Clinical Trials; Complex; Contrast Media; Country; Coupled; Detection; Development; Disease; Disease Progression; Effectiveness; Environment; FDA approved; Failure; Family; Funding; Future; Goals; Image; Imaging Techniques; Lead; Letters; Life; Manufacturer Name; Measurement; Mission; Molecular; National Institute on Aging; Optics; Outcome; Outcome Measure; Patients; Performance; Pharmaceutical Preparations; Phase; Plant Roots; Population; Positron-Emission Tomography; Predictive Value; Procedures; Process; Production; Quality Control; Quality of life; Radioactive; Reliability of Results; Reporting; Risk; Risk Factors; Running; Site; Solid; Standardization; Structure; System; Technology; Testing; Therapy trial; Tracer; Travel; Treatment Cost; Validation; Work; base; cost; drug development; experience; imaging study; improved; improved outcome; innovation; manufacturing facility; new therapeutic target; novel strategies; prevent; research and development; residence; skills; tau Proteins; therapy outcome

Positron Emission Tomography (PET) is the most powerful imaging procedure relied upon in the management of Alzheimer’s Disease (AD). It provides information on the molecular processes in the brain. PET imaging studies require short-lived radioactive contrast agents called PET tracers. Multiple PET tracers have a strong predictive value in AD. The long-term objective of the proposed work is availability of AD PET imaging to broad AD population, which enables (1) detection of disease in pre-symptomatic stage and (2) most effective clinical trials for development of AD therapies. Both of these impacts lead to improved outcomes for AD patients. Thereby, this project is considered highly relevant to the mission of National Institute on Aging (NIA). Trace-Ability plans to enable nationwide availability of AD PET imaging by eliminating production complexity rooted in release testing of AD PET imaging tracers. The enabling solution will be demonstrated with of [F-18]Flortaucipir (leading tau PET tracer with pending NDA) and [F-18]Florbetaben (FDA-approved Beta Amyloid PET tracer), thereby demonstrating solution’s universal applicability to multiple AD PET products. Proposed solution relies on complete automation of release testing on Tracer-QC platform that has been validated earlier with the most common PET tracer, F 18 Fludeoxyglucose (FDG) and demonstrated with [F-18]Florbetaben. Current experience has identified critical gaps that need to be filled in order to achieve broad commercial adoption of these products. By filling these gaps with R&D focused on 2 specific aims, proposed Direct to Phase II project enables rapid expansion of AD PET imaging to the broad AD population. Specific Aim 1: Achieve overall solution reliability required for broad commercial deployment by demonstrating failure of <0.1% at Trace-Ability and <1% in the field. This aim will first require thorough assessment of the currently known issues and potential risk factors. Next, we will define unique innovative technical solutions to each of the identified risks and issues. Then, implementation of each solution will be followed by a solid proof of its effectiveness. Once all solutions have been implemented, we will test the overall resulting reliability of the system in-house. After proving it to ourselves by demonstrating <0.01% failure rate, we will deploy systems in the field to prove the desired reliability of >99% in a variety of commercial AD PET tracer production environments. Specific Aim 2: Automated QC of AD PET tracers qualified at 4 commercial production facilities with a 30-day regulatory mechanism for adding new sites. The regulatory challenge for adoption of automated QC solution at new sites with new AD PET tracers is two-fold: (1) It requires thorough validation at each new site. (2) There is a 10-month FDA approval process for each new manufacturer. Phase II R&D will yield effective and innovative Performance Qualification (PQ) procedures that deliver solid proof of system’s analytical performance against pre-set acceptance criteria with a small number of special test runs at each new facility. In combination with a Type V DMF containing validation reports, such PQ will allow each new site to switch their release testing to Tracer-QC within 30 days following a CBE30 mechanism.

正电子发射断层扫描（PET）是管理中最强大的成像过程 阿尔茨海默氏病（AD）。它提供有关大脑分子过程的信息。宠物成像研究需要 短寿命的放射性对比剂称为宠物示踪剂。多个宠物示踪剂在AD中具有强大的预测价值。 拟议工作的长期目标是将广告宠物成像用于广泛的广泛人群，这 在症状前阶段和（2）开发AD的最有效临床试验中，启用（1）疾病检测 疗法。这两种影响都会改善AD患者的结局。因此，这个项目被认为很高 与国家老化研究所（NIA）的任务有关。 通过消除生产复杂性扎根的痕量能力计划，以使全国范围内的广告宠物成像可用 在AD PET成像示踪剂的释放测试中。启用解决方案将用[F-18] Flortaucipir证明 （带有待处理NDA的Tau Pet Tracer）和[F-18] Florbetaben（FDA批准的β淀粉样蛋白宠物示踪剂），从而 展示解决方案对多个AD PET产品的普遍适用性。 提议的解决方案发布了已验证的Tracer-QC平台上发布测试的完整自动化 早些时候，最常见的宠物示踪剂F 18 Fludeoxyglucose（FDG），并用[F-18] Florbetaben证明。 当前的经验已经确定了需要填补的关键差距，以实现广泛的商业采用 这些产品。通过用研发填补这些空白的重点是2个特定目标，拟议直接进行II期项目启用 AD PET成像快速扩展到广泛的广告群。 特定目标1：通过证明广泛的商业部署所需的总体解决方案可靠性 痕量时的失败<0.1％，现场<1％的失败。这个目标将首先需要对当前的彻底评估 已知问题和潜在的风险因素。接下来，我们将为每个已识别的独特的创新技术解决方案定义独特的创新技术解决方案 风险和问题。然后，将实施每个解决方案，之后将提供其有效性的可靠证明。一次 解决方案已实施，我们将测试系统内部的总体可靠性。在提供给 通过证明<0.01％的故障率，我们将在现场部署系统，以证明> 99％的理想可靠性 在各种商业广告宠物示踪剂生产环境中。 特定目标2：在4个商业生产设施中有资格的AD PET示踪剂自动化QC，有30天 添加新站点的监管机制。在新站点采用自动QC解决方案的监管挑战 有了新的AD PET示踪剂，有两个方面：（1）它需要在每个新站点进行彻底验证。 （2）有10个月的FDA 每个新制造商的批准过程。第二阶段研发将产生有效且创新的绩效资格 （PQ）提供了针对预设接受标准的系统分析性能的稳固证明的程序 每个新设施的特殊测试数量次数。结合包含验证报告的V型DMF类型，此类PQ CBE30机构后30天内将允许每个新站点将其发布测试切换为Tracer-QC。