SBIR Phase II: Development of a simple device that eliminates bottlenecks in radiopharmaceutical production

这个小型企业创新研究二期项目旨在为正电子发射断层扫描（PET）中使用的放射性药物制造提供具有成本效益的自动化质量控制（QC）系统。该系统将取代目前的QC程序，该程序涉及18个人工操作，8个目视评估，6个设备和8个放射性药物样品。该行业目前对人工操作、主观性和不可追溯记录的依赖阻碍了放射性药物制造的进步，并带来了合规风险。因此，将所有这些测试结合在一个平台上的自动化系统的引入，将促进PET成像技术在顶级医疗中心以外的应用。通过解决目前任何其他解决方案都无法解决的无线电药品生产中关键的现行良好生产规范（cGMP）合规性需求，该解决方案定位于快速采用。采用该系统后，预计制造工厂将实现20%的运营成本降低和50%的质量管理相关活动的时间减少。与引入自动化质量控制相关的合规成本降低将进一步提高采用率。这个项目将为平板阅读器技术的新应用打开大门，这种方法传统上局限于生物化学和诊断领域。第二阶段的工作包括四个技术目标。首先，该方法将被调整以最小化所需的样本量。在项目的第一阶段开发的方法需要0.5 ml的样品，这个值对于小型制造商来说不是最佳的。为了将该值降低到0.2 ml，将调整测试灵敏度，同时要记住潜在的动态范围权衡。其次，我们将设计一种支持商业制造商采用的塑料消耗品。目前的塑料原型部件只适用于拥有高技能人员的学术场所。为了减少所需的训练量，并扩大该方法的适用性，将设计一种新的塑料组件，以进一步实现样品装载的自动化。第三，我们将优化试剂的配方，使耗材试剂盒的保质期达到一年。第一阶段开发的试剂的保质期仍然未知。因此，将进行加速稳定性研究以估计分解过程的速率，并进行适当的更改以延长保质期。最后，我们将为新设计的套件开发一个试点生产流程，以支持早期安装。

This Small Business Innovation Research Phase II project aims to deliver a cost-effective automated quality control (QC) system for manufacturing of radioactive drugs used in Positron Emission Tomography (PET). This system will replace current QC procedures, which involve 18 manual operations, 8 visual assessments, 6 devices, and 8 samples of radioactive drugs. The industry's current reliance on manual operation, subjectivity and untraceable records impedes progress in radioactive drug manufacturing and presents compliance risks. Therefore, introduction of an automated system combining all these tests on a single platform will facilitate adoption of PET imaging technology beyond top tier medical centers. By addressing a critical current Good Manufacturing Practice (cGMP) compliance need in radio-pharmaceutical production, which cannot be addressed with any other solutions available today, this solution is positioned for rapid adoption. After adopting this system, it is expected that manufacturing facilities will realize 20% operating cost reduction and 50% reduction in time spent on QC-related activities. A reduced cost of compliance associated with introduction of automated QC will further contribute to the adoption rate. This project will open the door to new applications of plate reader technology, an approach which has been traditionally confined to the fields of biochemistry and diagnostics. This Phase II effort includes four technical objectives. Firstly, the approach will be adapted to minimize the required sample volume. Methods developed in Phase I of the project required 0.5 ml of sample, a value which is not optimal for small manufacturers. To bring this value down to 0.2 ml, test sensitivity will be adjusted, keeping in mind the potential dynamic range trade-offs. Secondly, we will design a plastic consumable that supports adoption by a commercial manufacturer. Current plastic prototype components are only suitable for academic sites with highly-skilled personnel. To reduce the amount of training required, and to expand the applicability of this method, a new plastic component will be designed in order to further automate sample loading. Third, we will optimize the formulation of the reagents to achieve a one-year shelf life for the consumable kit. The shelf life of the reagents developed in Phase I remains unknown. Therefore, accelerated stability studies will be performed to estimate the rates of decomposition processes, and appropriate changes will be made to enhance shelf life. Finally, we will develop a pilot production process for the newly-designed kit, in order to support early installations.