Evaluating Functional Equivalency as a Lyophilization Cycle Transfer Tool - Pharmaceutical Technology

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Evaluating Functional Equivalency as a Lyophilization Cycle Transfer Tool
The authors describe a comprehensive methodology for establishing functional equivalence among various lyophilizers.


Pharmaceutical Technology
Volume 33, Issue 9, pp. 54-70


Figure 1: Placement of weighed trays of vials containing mannitol solutions. Five weighed trays were located in the top, middle, and bottom shelves. One weighed tray was located in all the remaining shelves. In the full-load studies, the remaining space of the shelves was filled with unweighed trays containing vials with mannitol solutions. Total number of trays in partial load studies: A420FT = 23; B420FT and C220FT = 25. Total number of trays in full load studies: C220FT = 110; A420FT and B420FT = 210. (FIGURE IS COURTESY OF THE AUTHOR)
Sublimation rate studies using mannitol solution. Solutions of mannitol in water for injection (5.82% w/v) were filtered through 0.22-μm membrane filters, and about 62 mL of this solution was aseptically filled into 100-cm3 molded glass vials. Each vial was semi-stoppered with lyophilization stoppers (20-mm, double vented), and the vials were placed in close packing (60 vials each) in aluminum transfer trays with the surrounding rings or brackets. Some trays were identified with a suitable code. These trays were weighed using a top-loading scale situated inside the aseptic area. The vial-filled trays were then transported to the lyophilizer chamber, the bottoms of the trays were pulled out (leaving the ring in place), and vials were directly transferred onto the surface of the shelves.


Table II: Lyophilization cycle used for sublimation rate studies.
Figure 1 shows the placement of the weighed trays containing vials in the lyophilizer chambers. Weighed trays were distributed throughout the chamber to obtain water loss data from all the locations. Once loaded, the lyophilization cycle was initiated as described in Table II. Upon completion of the lyophilization cycle sequence, the trays were unloaded and the marked trays were weighed using the same top-loading scale. The loss of water caused by sublimation drying in each tray was calculated on the basis of the difference in weights (final weight of the tray minus the initial weight). Using this methodology, drying rates were compared in lyophilizers with partially loaded trays (23 trays in C220FT and 25 trays in A420FT and B420FT) in the lyophilizer chambers as well as in fully loaded (110 trays in C220FT and 210 trays in A420FT/B420FT) conditions.

Comparison of process parameters during cycles. Shelf-temperature, condenser-temperature, and chamber-pressure profiles during the lyophilization runs were compared in lyophilizers under partial-load and full-load conditions, and the process parameter data were analyzed following the runs to determine the extent of agreement from unit to unit.


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