Development and Experimental Verification of Fundamental Models to Enable Implementation of Microwave-Assisted Freeze Drying

项目摘要/摘要 物理科学公司(PSI)，与康涅狄格大学(UConn)合作，与 来自默克公司的行业参与，建议开发和验证微波的基本模型- 辅助冷冻干燥(MAFD)，以实现其在制药生产中的实施。这一努力 将利用开发和测试的瓶装传统货架冷冻干燥的主要干燥模型 来自国家生物制药创新研究所(NIIMBL)的支持。我们的目标是 为了建立MAFD冷冻一次干燥或冰升华阶段的热质传递模型。 干燥，最耗时也是最关键的阶段。该模型将预测产品的温度 根据容器系统的输入参数(例如小瓶， 托盘或双腔注射器)、产品配方(例如介电性能、耐干性等)、 以及工艺条件(如微波频率、微波功率、腔体压力)。 该计划支持监管科学的进步，以促进实施 制药行业的新兴制造技术。微波辅助冷冻干燥(MAFD) 正在成为传统冷冻干燥的替代方案，因为MAFD可以显著降低加工成本 与传统的冷冻干燥相比，在保持产品功效和稳定性的同时，节省了时间。例如, 研究表明，与传统的冷冻干燥相比，使用MAFD可以减少大约80%的周期时间。 MAFD在食品工业中更常用，但尚未应用于食品的干燥 大规模生产医药产品。这部分是由于缺乏对配方反应的了解 对于微波能量，以及MAFD工艺中的热量和传质，确保高效的工艺设计 同时保持产品质量属性。这项计划的成功完成将带来一场热潮。 并建立了MAFD的传质模型和配方微波功率吸收数据库 工业用来实现MAFD流程。从传统冷冻干燥转型 TO MAFD将减少加工成本和周期时间，并实现更敏捷的制造 包括按需工艺和半连续工艺。 在当前这场全球大流行期间，这一努力尤其重要。当前的行政管理 新冠肺炎疫苗受到冷链储存要求的限制。作为新冠肺炎疫苗接种计划 从应急响应过渡到常规管理、生产和分配经济学 将变得更加关键。未来新冠肺炎疫苗的发展很可能集中在冷冻方面 用于产品稳定和分配的干燥。许多常见的疫苗需要冷冻干燥，包括 预防麻疹、黄热病、乙型流感、卡介苗、甲型H1N1等。经济型冷冻干燥的发展 周期将是世界各地制造设施生产新冠肺炎疫苗的关键。

Project Summary/Abstract Physical Sciences Inc. (PSI), in collaboration with the University of Connecticut (UConn), and with industry participation form Merck, proposes to develop and verify a fundamental model of Microwave- Assisted Freeze Drying (MAFD) to enable its implementation for pharmaceutical manufacturing. This effort will leverage primary drying models of traditional shelf-based freeze drying in vials developed and tested with support from the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). Our goal is to develop a heat and mass transfer model of the primary drying, or ice sublimation phase of MAFD freeze- drying, the most time consuming and critical phase. The model will predict the temperature of the product throughout primary drying and the drying time based on input parameters for the container system (e.g. vial, tray or dual chamber syringe), the product formulation (e.g. dielectric properties, resistance to drying, etc.), and the process conditions (e.g. microwave frequency, microwave power, chamber pressure). This program supports the advancement of regulatory science to facilitate the implementation of emerging manufacturing technology in the pharmaceutical sector. Microwave-assisted freeze drying (MAFD) is emerging as an alternative to traditional freeze drying as MAFD can significantly reduce processing costs and time compared to traditional freeze drying while maintaining product efficacy and stability. For example, studies have shown an approximately 80% reduction in cycle time using MAFD over traditional freeze drying. MAFD has more commonly been used in the food industry, and has not been applied to drying of pharmaceutical products at a large scale. This is partially due to a lack of knowledge of formulation response to microwave energy, and heat and mass transfer in MAFD processes to ensure efficient process design while maintaining product quality attributes. The successful completion of this program will result in a heat and mass transfer model of MAFD and a database of formulation microwave power absorption that can be used by industry to enable implementation of MAFD processes. Transitioning from traditional freeze drying to MAFD will result in reduced processing costs and cycle times and enable more agile manufacturing including on-demand and semi-continuous processes. This effort is particularly relevant during this current global pandemic. Administration of the current COVID-19 vaccines was limited by cold chain storage requirements. As COVID-19 vaccination programs transition from emergency response to routine administration, the economics of production and distribution will become more crucial. It is likely that future development of the COVID-19 vaccines will focus on freeze drying for product stabilization and distribution. Many common vaccines require freeze-drying, including those to prevent measles, yellow fever, Hib, BCG, H1N1, etc. Development of economical freeze-drying cycles will be critical for production of COVID-19 vaccines in manufacturing facilities around the world.