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

项目概要/摘要 物理科学公司(PSI)，与康涅狄格大学（UConn）合作， 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），使其能够用于制药生产。这一努力 将利用传统的基于货架的小瓶冷冻干燥的主要干燥模型， 国家生物制药制造创新研究所（NIIMBL）的支持。我们的目标是 建立了MAFD冷冻过程中初级干燥或冰升华阶段的传热传质模型。 干燥，最耗时和关键的阶段。该模型将预测产品的温度 在整个初级干燥和干燥时间中基于容器系统的输入参数（例如小瓶， 托盘或双室注射器），产品配方（例如介电性能、抗干燥性等）， 和工艺条件（例如微波频率、微波功率、腔室压力）。 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） 由于MAFD可以显著降低加工成本， 和时间，同时保持产品的功效和稳定性。比如说， 研究表明使用MAFD比传统的冷冻干燥减少了大约80%的循环时间。 MAFD更常用于食品工业中，并且尚未应用于食品的干燥。 大规模生产药品。这部分是由于缺乏对制剂反应的了解 微波能量以及MAFD工艺中的热量和质量传递，以确保高效的工艺设计 同时保持产品质量属性。这一计划的成功完成将导致一个热 建立了MAFD的传质模型和微波功率吸收配方数据库， 被工业界用来实现MAFD过程。从传统的冷冻干燥 MAFD将降低加工成本和周期时间，并实现更敏捷的制造 包括按需和半连续工艺。 在当前这一全球大流行病期间，这一努力尤其具有现实意义。当前的行政管理 COVID-19疫苗受到冷链储存要求的限制。随着COVID-19疫苗接种计划 从应急响应到日常管理的过渡，生产和分配的经济性 将变得更加重要。COVID-19疫苗的未来开发可能会集中在冷冻方面， 干燥以使产品稳定和分布。许多常见的疫苗需要冷冻干燥，包括 预防麻疹、黄热病、Hib、BCG、H1N1等的冻干剂 对于全球各地生产设施的COVID-19疫苗生产而言，周期将至关重要。

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.