Freeze-drying cycle duration

Although the measurement of product temperature with probes inserted nearly to the bottom of the vials or ampoules is often questioned for many reasons, we use this method routinely to evaluate the duration of primary drying and the maximum primary drying temperature as shown in Figure 1. During prevalidation trials, we have run a series of more or less extreme freeze-drying cycles for sucrose and lactose formulations. The pellets produced were examined for... 

Temperature of shelves during the successive freeze-drying steps Duration of the soaks and of the temperature ramps Total cycle time... 

For products in vials, cycles of fixed duration are easily implemented, as the vials can be automatically stoppered. However, with ampoules it may be desirable to have cycles of variable duration for schedule-related reasons. An elegant way to avoid variations in freeze-drying duration is to stop the lyophilization after a fixed time and to store the ampoules under dry sterile nitrogen in the lyophilizer until sealing is possible. 

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