Freeze Dryer Characterization using Water Sublimation Tests and Applications for Lyocycle Scale-Up

Conference Module

Freeze Dryer Characterization using Water Sublimation Tests and Applications for Lyocycle Scale-Up
Tracks:
Contributed Papers: Process Scale-Up, Validation, and Technology Transfer
Date/Time:
Tuesday, October 31, 2006 2:00 PM - 6:00 PM
Location:
T3264

Description:
Purpose: To compare lab, pilot, and production-scale freeze dryers using water sublimation tests. Sublimation tests will be used to (i) identify shelf to shelf variation and map the lyophilizer with respect to sublimation rate (ii) evaluate the maximum sublimation rate attainable without overloading the freeze dryer (iii) calculate the vial heat transfer coefficient for various locations in the freeze dryer.
Methods: Using Water for Injection (WFI), the sublimation rate, determined gravimetrically, was evaluated for lab, pilot, and production-scale freeze dryers. Steady-state heat and mass transfer relationships relevant to freeze drying were used to calculate the heat transfer coefficients and overloading conditions for each freeze dryer evaluated. The heat transfer coefficient was used to model primary drying using PassageÒ Freeze Drying software.
Results: The sublimation tests in trays demonstrated that failure of the freeze dryer (e.g. loss of pressure control) might occur if the sublimation rate exceeds the thermal load capacity. The sublimation tests also demonstrated that the sublimation rate in vials increased towards the rear of the freeze drying chamber (closest to the pipe separating chamber and condenser) and typically the lowest sublimation rates were observed on the middle shelf, indication of the “coldest zone” of the lyophilizer. The heat transfer coefficient for various locations on a shelf is also dependent on the scale of the freeze dryer. For example the heat transfer coefficient for center vials in a pilot-scale freeze dryer was approximately half of the heat transfer coefficient calculated for center vials in a lab-scale freeze dryer. The PassageÒ Freeze Drying software predicted relative drying times that were consistent with experimental data for sublimation endpoint for various size lyophilizers.
Conclusion: Data acquired from water sublimation tests can be used to ensure the freeze dryer can sustain a thermal load for specified lyocycle conditions. Sublimation test data is also used to determine hot/cold zones in the lyophilizer that should be identified as areas interest for post-lyophilization testing such as water content and reconstitution time. Sublimation test data can be also be used to compare equivalence of various capacity dryers and the PassageÒ Freeze Drying software can be used to predict the endpoint of ice sublimation which is extremely valuable for lyocycle scale-up.