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

该项目的广泛的长期目标是使PET药物制造业能够提供最多样化的 成像产品组合，可在一系列临床适应症中实现最有效的诊断成像。电流 限制在于PET药物制造商的生产量和法规遵从性。拟议项目涉及以下两个方面： 通过对PET药物生产中最复杂、最主观的方面--质量控制进行现代化改造，克服这些局限性。它建立 上一个U 01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-氟脱氧葡萄糖），并将经验证的益处扩展到PET药物的全部组合。 在Tracer-QC能够在PET药物制造中产生全行业影响之前，需要解决几个障碍。 (1)目前，每种新的PET药物都需要开发一种分析方法和一种独特的一次性试剂盒， 药Trace-Ability迄今已开发并验证了3种药物特异性试剂盒。但随着近100（和不断增长）PET 由于我们正在使用的产品和临床试验中，我们无法通过为每种新的PET药物部署试剂盒来跟上步伐。(2)使用Tracer- 质量控制是非常有效的，它在每个新的地点部署，然后由FDA进行详细的审查是漫长的，需要 这是许多制药企业所没有的。(3)迄今为止开发的创新工具包具有效率和可靠性 作为成功的关键标准，不幸的是，这导致了它们的高成本，这是行业广泛采用的另一个障碍。 拟议的项目将解决采用的3个障碍，并使整个PET行业以及FDA检查员 从Tracer-QC创新提供的独特的简单性、安全性、一致性和合规性中受益。 具体目标1：用户可配置通用Tracer-QC解决方案，以支持任何PET药物的QC。该溶液 将允许用户选择任何组合从列表中的20个（和增长）可能的QC测试就去没有方法 开发他们感兴趣的示踪剂。具体目标2：可提供给最终用户的试剂盒的经验证生产， 100美元或更少，不影响质量。这一目标将需要重新设计工具包及其制造过程。 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” 任何示踪剂通过CBE-30机制。为了实现这一目标，我们将需要制定和验证“推出 与FDA密切合作，U 01机制提供了一个独特的机会。有几 设想的机制包括可比性方案或DMF以及统一的PQ程序等。“推出 载体”将首先在学术场所进行验证，然后在商业PET药物中进行实施和评估。 这是Tracer-QC在整个行业中应用的关键一步。 预期成果：（1）提高PET药物的质量和整个行业的放行检测效率;（2） PET药物生产知识体系的现代化，使其更加稳健、可预测和具有成本效益;（3）21 在行业层面解决CFR第212部分合规性问题：（4）简化PET药物生产的监督， FDA;（5）基于科学的质量标准;（6）操作员安全;（7）PET药物生产行业的增长 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.