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

实现微波辅助冷冻干燥的基本模型的开发和实验验证

• 批准号: 10602061
• 负责人: Emily S Gong
• 金额: $ 99.94万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602061
• 关键词: Development; Experimental; Verification; Fundamental; Models

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.

项目摘要/摘要 物理科学公司（PSI），与康涅狄格大学（UConn）合作，并与 默克公司的行业参与形式，提议开发和验证微波的基本模型 辅助冷冻干燥（MAFD），以实现其用于制药制造的实施。这项努力 将利用开发和测试的小瓶中基于架子的冻干的主要干燥模型 国家制造生物制药（Niimbl）的国家创新研究所的支持。我们的目标是 开发主要干燥的热和传质模型，或MAFD冻结的冰升华阶段 干燥，最耗时和关键阶段。该模型将预测产品的温度 在整个初级干燥和基于容器系统的输入参数的干燥时间（例如，小瓶， 托盘或双室注射器），产品配方（例如介电性能，抗干燥等）， 以及过程条件（例如微波频率，微波功率，腔室压力）。 该计划支持监管科学的发展，以促进实施 制药领域的新兴制造技术。微波辅助冷冻干燥（MAFD） 由于MAFD可以大大降低处理成本 与传统的冷冻干燥相比，时间和时间在保持产品功效和稳定性的同时。例如， 研究表明，使用MAFD比传统的冷冻干燥降低了大约80％的循环时间。 MAFD更常用于食品行业，尚未应用于干燥 药品大规模。这部分是由于缺乏配方响应的知识 进行微波能量以及MAFD过程中的热量和传质，以确保有效的工艺设计 同时保持产品质量属性。该计划的成功完成将导致热量 MAFD的传质模型和配方微波功率吸收数据库，可以是 行业用于实施MAFD流程。从传统冷冻干燥过渡 MAFD将导致处理成本和周期时间减少，并启用更多敏捷制造 包括按需和半连续过程。 在当前的全球大流行期间，这项工作尤其重要。电流管理 Covid-19疫苗受冷链存储要求的限制。作为19号疫苗接种计划 从紧急响应到常规管理，生产和分销经济学的过渡 将变得更加关键。 Covid-19-19疫苗的未来开发可能会集中于冻结 干燥用于产品稳定和分布。许多常见的疫苗需要冷冻干燥，包括 那些防止麻疹，黄热病，HIB，BCG，H1N1等。 周期对于世界各地的制造设施中的Covid-19疫苗生产至关重要。