【国外标准】 Standard Practice for Product Temperature and Equipment Pressure Instrumentation in Pharmaceutical Freeze Drying

3.1 This practice deals with recommended best practices for freeze dryer instrumentation, particularly which is used for monitoring the status of the product during freeze drying and perhaps for equipment capability testing. Temperature and pressure are both critical variables affecting heat transfer, mass transfer, process efficiency, and product quality. For this reason, particular emphasis is placed on product temperature and pressure measurement within the freeze dryer. The methods discussed in this guide are limited to techniques that are equally applicable at both laboratory and production scale.3.2 Finally, it is recognized that “best practice” changes over time as new technology matures and process understanding deepens.1.1 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.1.2 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.1.3 Aseptic filling and sterilization practices are outside the scope of this practice. These are recommendations to assist users in selecting best practices and they are not intended to supersede or replace regulatory requirements.1.4 Units—The values stated in SI units are to be regarded as the standard. No other units of measurement are included in this standard with the exception of mTorr for pressure measurement1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.1.6 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.