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

在 PET 放射性药品制造行业广泛实施质量控制现代化通用解决方案。

• 批准号: 10675471
• 负责人: Arkadij Elizarov
• 金额: $ 100万
• 依托单位: TRACE-ABILITY, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675471
• 关键词: Broad; Implementation; universal; solution; quality

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.

该项目的广泛长期目标是使宠物药物制造业能够提供最潜水员 成像产品的投资组合需要在一系列临床适应症上进行最有效的诊断成像。当前的 限制是宠物药物制造商的吞吐量和法规依从性。拟议的项目解决了这两个 这些局限性通过使宠物药物生产的最复杂和主观方面现代化 - 质量控制。它建立 关于提供解决方案的先前U01项目的成功，称为最常见的宠物示踪剂的Tracer-QC （18F氟脱氧葡萄糖），并将经过验证的福利扩展到宠物药物的全部产品组合。 在Tracer-QC能够在宠物药物制造中产生范围内的影响之前，需要解决一些障碍。 （1）当前，每种新宠物药物都需要开发分析方法，并为此量身定制的独特的一次性套件 药品。迄今为止，痕量能力已经开发并验证了3个药物特异性试剂盒。但是有接近100（和成长）的宠物 使用和临床试验中的产品，我们无法通过为每种新宠物药物部署套件来保持步调。 （2）使用示踪剂 - QC非常有效，其在每个新站点的部署，然后是FDA的详细审查很长，需要 许多宠物药物制造商没有的资源。 （3）迄今为止开发的创新套件具有效率和可靠性 作为成功的关键标准，不幸的是，这导致了他们的高成本，这是整个行业采用的另一个障碍。 拟议的项目将解决这3个障碍，以采用并使整个宠物行业以及FDA检查员能够 从Tracer-QC创新提供的独特的简单，安全性，统一性和合规性中受益。 特定目的1：通用示踪QC解决方案可由用户配置以支持任何PET药物的QC。这个解决方案 将允许用户从20个（并增长）可能的QC测试列表中选择任何组合，而无需方法 开发他们感兴趣的示踪剂。特定目标2：经过验证的套件生产，可以向最终用户提供 $ 100或更少，没有折衷质量。这个目标将需要重新设计套件及其制造工艺。 特定目标3：监管“推出车辆”，允许商业宠物药物制造商实施Tracer-QC 对于任何通过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“推出 车辆”与FDA密切合作，U01机制为此提供了独特的机会。有几个 设想的机制包括具有统一PQ程序的可比性协议或DMF。 “推出 车辆”将首先在学术网站上进行验证，然后在商业宠物药物中实施和评估 制造地点，从而迈出了整个行业采用Tracer-QC的关键一步。 预期结果：（1）宠物药物的质量提高和整个行业的释放测试效率； （2） 宠物药物生产体系的现代化使其更加稳健，可预测和成本效益； （3）21 CFR第212部分在行业层面解决的合规性问题：（4）简化对宠物药物生产的监督 fda; （5）基于科学的质量标准； （6）操作员安全； （7）宠物药物生产行业的增长 全国患者和医生的宠物产品组合更广泛。