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.

正电子发射断层扫描(正电子发射断层扫描)是最强大的成像程序依赖于管理 阿尔茨海默病(AD)。它提供了有关大脑中分子过程的信息。宠物成像研究需要 被称为PET示踪剂的短命放射性造影剂。多种PET示踪剂对AD有很强的预测价值。 拟议工作的长期目标是AD PET成像在广泛的AD人群中的可用性， 使(1)在症状前期发现疾病和(2)对AD的发展进行最有效的临床试验 治疗。这两种影响都会改善AD患者的预后。因此，这个项目被高度评价。 与国家老龄研究所(NIA)的使命相关。 TraceCapability计划通过消除根植于生产的复杂性，在全国范围内提供AD PET成像 在AD PET成像示踪剂的释放测试中。启用解决方案将通过[F-18]Flortaucipir进行演示 (具有未决NDA的领先tau PET示踪剂)和[F-18]Florbetaben(FDA批准的Beta淀粉样PET示踪剂)，从而 展示了该解决方案对多种AD PET产品的普遍适用性。 建议的解决方案依赖于Tracer-QC平台上经过验证的发布测试的完全自动化 早期使用最常见的PET示踪剂F18氟脱氧葡萄糖(FDG)，并使用[F-18]Florbetaben演示。 目前的经验已经确定了需要填补的关键空白，以便实现广泛的商业采用 这些产品。通过以专注于两个具体目标的研发来填补这些空白，拟议的Direct to II项目实现了 快速将AD PET成像扩展到广泛的AD人群。 具体目标1：通过演示实现广泛商业部署所需的整体解决方案可靠性 跟踪不合格率为0.1%，现场不良率为1%。这一目标首先需要彻底评估目前 已知问题和潜在风险因素。接下来，我们将为每一个已确定的 风险和问题。然后，每个解决方案的实施都将得到其有效性的坚实证明。一次过 在解决方案已经实施后，我们将在内部测试系统的整体可靠性。在证明了这一点之后 通过证明故障率为0.01%，我们将在现场部署系统，以证明&gt；99%的预期可靠性 在各种商业AD PET示踪剂生产环境中。 具体目标2：AD PET示踪剂的自动化质量控制在4个商业生产设施合格，为期30天 增加新网站的监管机制。在新地点采用自动化QC解决方案面临的监管挑战 使用新的AD PET示踪剂有两个方面：(1)它需要在每个新的地点进行彻底的验证。(2)有10个月的FDA 每个新制造商的审批流程。第二阶段研发将产生有效和创新的绩效资格 (PQ)程序，根据预先设定的验收标准提供系统分析性能的坚实证据 每个新工厂的特殊测试运行次数。与包含验证报告的类型V DMF相结合，例如PQ 将允许每个新站点在遵循CBE30机制后的30天内将其发布测试切换到Tracer-QC。

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.