Instrument for Holographic Characterization of Protein Aggregates

项目（摘要） ! 形成蛋白质三维结构的关键力量是 也负责不必要的和经常危险的蛋白质聚集体， 基于蛋白质的疗法蛋白质聚集发生在细胞的每个阶段， 从开发、配方、生产到运输、储存 和使用点。FDA在其2014年行业指南中建议，“这是 对于治疗性蛋白质产品的制造商来说， “尽可能地聚合”，同时承认技术确实 目前还不存在实现这一目标，特别是在关键的亚可见 范围从100 nm到10微米。因此，迫切需要 可以评估蛋白质的大小分布和形态的仪器 在这个尺寸范围内的聚合物。母公司SBIR第二阶段计划正在满足这一要求 需要开发一种基于全息视频显微镜的仪器 (HVM)快速可靠地检测和计数蛋白质聚集体， 监测药物配方。第二阶段工作的结果 向大型制药公司销售仪器， 高校早期采用者和潜在客户已经确定了关键 使他们能够部署这种技术的额外能力 从配方开发和计量到质量的过程阶段 评估和制造过程控制，Spheryx的技术 提高产品质量和降低制造成本的潜力。这 IIB阶段的工作将扩展Spheryx的能力，以满足他们的需求。的 本工作的具体目标是：（1）检测和区分当前的污染物 具有挑战性的生物制剂制造，包括气泡和金属颗粒;（2） 诊断处理引起的成分变化，包括由 剪切力以及加工过程中的粘度和温度变化。两 要实现这些额外的目标，需要硬件和软件创新 能力的这项工作的成果将是一个强大的新的制造工具 具有满足生物制品行业关键需求的独特能力。 ! !

Project(Summary( ! The very forces critical to creating the three-dimensional structure of proteins are also responsible for unwanted and often dangerous protein aggregates in protein-based therapeutics. Protein aggregation occurs at every stage in the pipeline, from development, formulation, and manufacturing to shipping, storage and point of use. The FDA advised in its 2014 Guidance for Industry that “It is critical for manufacturers of therapeutic protein products to minimize protein aggregation to the extent possible'', while acknowledging that technology does not currently exist to accomplish this goal, particularly in the critical sub-visible range from 100 nm to 10 microns. Thus, there is a pressing and unmet need for instrumentation that can assess the size distribution and morphology of protein aggregates in this size range. The parent SBIR Phase II program is meeting this need by developing an instrument based on holographic video microscopy (HVM) to detect and count protein aggregates rapidly and reliably enough for monitoring pharmaceutical formulations. Results from the Phase II work has resulted in sales of instruments to major pharmaceutical companies and universities. Early adopters and prospective customers have identified key additional capabilities that would enable them to deploy this technique at all stages of their process from formulation development and metrology into quality assessment and manufacturing process control where Spheryx’s technology has the potential to improve product quality and reduce manufacturing costs. This Phase IIB work will extend Spheryx’s capabilities to meet their needs. The specific aims of this work are: (1) detect and distinguish contaminants currently challenging biologics manufacturing including air bubbles and metal particles; (2) diagnosing handling-induced composition changes including changes caused by shear forces and by viscosity and temperature variation during processing. Both hardware and software innovations will be needed to accomplish these additional capabilities. The results of this work will be a powerful new manufacturing tool with unique capabilities to meeting critical needs for the biologics industry. ! !