Broad Implementation of a universal solution for quality control modernization in PET radio-pharmaceutical manufacturing industry.

该项目广泛的长期目标是使PET药物制造行业能够供应最多样化的 成像产品组合需要在一系列临床适应症中进行最有效的诊断成像。当前 限制是在生产能力和PET药物制造商的法规遵从性方面。拟议的项目解决了两个问题 这些限制是通过使PET药物生产中最复杂和最主观的方面--质量控制现代化来实现的。它构建了 关于之前的U01项目的成功，该项目为一种最常见的PET示踪剂提供了称为Tracer-QC的解决方案 (18F-氟代脱氧葡萄糖)，并将验证的益处扩大到PET药物的全部产品组合。 在Tracer-QC能够在PET药物制造领域产生行业影响之前，需要解决几个障碍。 (1)目前，每一种新的PET药物都需要开发一种分析方法和一种为之量身定做的独特的一次性试剂盒 毒品。到目前为止，TraceCapability已经开发并验证了3种药物专用试剂盒。但有近100种(而且还在不断增长)的聚酯 在产品的使用和临床试验中，我们无法通过为每一种新的PET药物部署试剂盒来跟上步伐。(2)在使用示踪剂时- QC是非常高效的，它在每个新的地点部署，然后由FDA进行详细审查是漫长的，并且需要 许多PET药物制造商没有的资源。(3)迄今开发的创新试剂盒具有效率和可靠性 作为成功的关键标准，这不幸导致了它们的高成本，这是整个行业采用的另一个障碍。 拟议的项目将解决采用的3个障碍，并使整个聚酯行业以及FDA检查员能够 受益于Tracer-QC创新提供的独特的简单性、安全性、一致性和合规性。 具体目标1：通用示踪器-用户可配置的质量控制解决方案，以支持任何PET药物的质量控制。此解决方案 将允许用户从20个(并且不断增加)的可能的QC测试列表中选择任意组合 用于他们感兴趣的示踪剂的开发。具体目标2：可在以下位置向最终用户提供的经过验证的套件生产 100美元或更少，而不影响质量。这一目标将需要重新设计成套设备及其制造工艺。 具体目标3：允许商业PET药物制造商实施Tracer-QC的监管“推广工具” 任何通过CBE-30机制的示踪剂。为了实现这一目标，我们将需要开发和验证“推广” 车辆“与FDA密切合作，U01机制为其提供了独特的机会。有几个 设想的机制包括可比性协议或具有统一PQ程序的DMF等。“展会” Vehicle“将首先在学术现场进行验证，然后在商业PET药物上进行实施和评估 从而为全行业采用Tracer-QC迈出了关键的一步。 预期结果：(1)提高了PET药物的质量和整个行业的释放测试效率；(2) 使PET药物生产知识体系现代化，使其更稳健、可预测和更具成本效益；(3)21 CFR第212部分在行业层面解决的合规性问题：(4)简化了对PET药物生产的监督 FDA；(5)以科学为基础的质量标准；(6)操作员安全；(7)PET药品生产行业的增长 为全国的患者和医生提供更广泛的PET产品组合。

This project’s broad long-term objective is to enable the PET drug manufacturing industry to supply the most diverse portfolio of imaging products demanded for most effective diagnostic imaging across a range of clinical indications. Current limitations are in throughput and regulatory compliance of PET drug manufacturers. Proposed project addresses both of these limitations by modernizing the most complex and subjective aspect of PET drug production – quality control. It builds on the success of the prior U01 project that has delivered a solution, called Tracer-QC for one most common PET tracer (18F-fluorodeoxyglucose) and expands the validated benefits to the full portfolio of PET drugs. Several barriers need to be addressed before Tracer-QC can deliver an industry-wide impact in PET drug manufacturing. (1) Currently each new PET drug requires development of an analysis method and a unique disposable kit tailored to that drug. Trace-Ability has developed and validated 3 drug-specific kits to date. But with close to 100 (and growing) PET products in use and clinical trials, we cannot keep pace by deploying kits for each new PET drug. (2) While use of Tracer- QC is very efficient, its deployment at each new site followed by detailed review by the FDA is lengthy and requires the resources that many PET drug manufacturers do not have. (3) Innovative kits developed to date had efficiency and reliability as key criteria for success, which unfortunately led to their high cost which is another obstacle to industry-wide adoption. Proposed project will address the 3 roadblocks to adoption and enable the whole PET industry as well as the FDA inspectors to benefit from the unique simplicity, safety, uniformity and compliance offered by Tracer-QC innovation. Specific Aim 1: Universal Tracer-QC solution configurable by the user to support QC of any PET Drug. This solution will allow the user to choose any combination from a list of 20 (and growing) possible QC tests on-the-go without method development for their tracer of interest. Specific Aim 2: Validated production of kits that can be offered to the end user at $100 or less without compromising quality. This aim would require redesign of both the kit and its manufacturing processes. Specific Aim 3: Regulatory “rollout vehicle” that allows commercial PET drug manufacturers to implement Tracer-QC for any tracer via CBE-30 mechanism. In order to achieve this aim, we will need to develop and validate the “rollout vehicle” in close collaboration with the FDA, for which the U01 mechanism offers a unique opportunity. There are several envisioned mechanisms including comparability protocol or DMF with uniform PQ procedures among others. The “rollout vehicle” will be first validated at an academic site followed by implementation and assessment at commercial PET drug manufacturing sites, thus making the critical step to industry-wide adoption of Tracer-QC. Expected outcomes: (1) Improved quality of PET drugs and efficiency of release testing across the whole industry; (2) Modernization of PET drug production body of knowledge making it more robust, predictable and cost-effective; (3) 21 CFR Part 212 compliance issues addressed at the industry level: (4) Simplified oversight of PET drug production by the FDA; (5) Science-based quality standard; (6) Operator safety; (7) growth of PET drug production industry delivering broader portfolio of PET products to patients and doctors nationwide.