Baxter Medical Products R&D, LLC\ 927 S. Curry Pike, Bloomington, Indiana, 47403, USA.
Pfizer Global Research, Andover, Massachusetts, USA.
AAPS PharmSciTech. 2017 Oct;18(7):2379-2393. doi: 10.1208/s12249-017-0733-1. Epub 2017 Feb 15.
Recommended best practices in monitoring of product status during pharmaceutical freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments-thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed-thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for freeze dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.
推荐了在药物冷冻干燥过程中监测产品状态的最佳实践，重点介绍了适用于实验室和生产规模的方法。关于产品温度测量，讨论了任何类型的测量探头相关的不确定性源，以及两种最常见的温度测量仪器——热电偶和电阻温度探测器（RTD）之间的重要差异。讨论了两种类型的压力传感器——热导式仪表和电容压力计，其中皮拉尼计是首选的热导式仪表。建议在具有外部冷凝器的冷冻干燥器上的产品腔室和冷凝器上同时使用两种类型的压力表，并且讨论了这种建议的理由。还简要回顾了值得进一步研究的过程监测开发技术，包括无线产品温度监测、制造规模的可调谐二极管激光吸收光谱学、热通量测量和质谱作为过程监测工具。
