Recommended Best Practices in Freeze Dryer Equipment Performance Qualification: 2022

Abstract

Best practices for performing freeze dryer equipment qualification are recommended, focusing on identifying methods to quantify shelf thermal uniformity (also known as “shelf surface uniformity”), equipment capability, and performance metrics of the freeze dryer essential to the pharmaceutical Quality by Design paradigm. Specific guidelines for performing shelf temperature mapping, freeze dryer equipment limit testing (the capability curve), and condenser performance metrics have been provided. Concerning shelf temperature mapping and equipment capability measurements, the importance of paying attention to the test setup and the use of appropriate testing tools are stressed. In all the guidelines provided, much attention has been paid to identifying the balance between obtaining useful process knowledge, logistical challenges associated with testing in the production environment vs that at laboratory scale, and the frequency of the testing necessary to obtain such useful information. Furthermore, merits and demerits of thermal conditions maintained on the cooled surfaces of the freeze dryer condenser have been discussed identifying the specific influence of the condenser surface temperature on the process conditions using experimental data to support the guidelines. Finally, guidelines for systematic leak rate testing criteria for a freeze dryer are presented. These specific procedural recommendations are based on calculations, measurements, and experience to provide useful process and equipment knowledge. Graphical Abstract

Best Practices and Guidelines (2022) for Scale-up and Technology Transfer in Freeze Drying Based on Case Studies. Part 2: Past Practices, Current Best Practices, and Recommendations

“…d) Vial (container) heat transfer coefficient (K v or K v,s ) as a function of pressure and position (edge effect). Ongoing efforts on best practice recommendations for equipment qualification are summarized in [8].…”

“…It is recommended to have predetermined condenser temperature set points during the process. In addition, having moderately higher condenser temperature set points such as − 60°C will be advantageous for ice distribution on condenser coils as compared to extremely low set points such as − 110°C [8,47]. The type of refrigeration system will also influence the freezing process and affect the cooling rate of the shelves.…”