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 instrumentsthermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussedthermal 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 UnitsThe 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 measurement. 1.5 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.
Keywordspressure measurement; process analytical technology; temperature measurement; freeze drying; process instrumentation; best practices
First, uncertainty over best practices in these areas of freeze-drying operations can lead to delays resulting from lengthy internal debate over what really constitutes best practice, and it seems common that unnecessarily conservative positions are taken, particularly when deep expertise in the subject may be lacking. Second, there is often not enough reflective thought about the scientific and engineering reasons behind such practices. Because we have always done it that way is an all-too common response. It is hoped that the sharing of information between companies will promote a deeper understanding of the science and engineering of pharmaceutical freeze drying, which is a fundamental component of the Quality by Design paradigm. Finally, on a more practical level, none of us want to be taken by surprise during discussions with any regulatory agency and have no thoughtful response to offer when asked about the reasoning behind our practices. The information is provided for use by development scientists, validation and operations engineers, technicians, and operators alike in the bio/pharmaceutical manufacturing industry and the practices outlined in the documents are designed for use by anyone in the freeze-drying community including quality control and government agencies.
The title and scope are in draft form and are under development within this ASTM Committee.Back to Top
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