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

For the direct comparison of lyophilizer units A420FT (420-ft2 shelf surface area), B420FT (same model as A420FT but has longer vapor path between the condenser and vacuum pumps), and C220FT (220-ft2 shelf surface area), vials containing mannitol solutions were used and the initial rate of sublimation drying was studied in Type I borosilicate glass vials of 100-cm3 capacity. The concentration of mannitol was kept at 5.82% w/v in water for injection (which corresponded to the percent solid composition of a solution for lyophilization of a commercial product). After completion of the freezing process, sublimation drying was conducted for as long as 16 h at the first shelf-temperature regimen of primary drying. The cycle was interrupted and the amount of water lost because of sublimation was calculated by the difference in weights. The drying rates of trays of corresponding locations among three lyophilizer units were compared.

Cycle parameters for these trials were selected on the basis of existing production cycles executed in the units under study. The rationale for conducting only a partial cycle was to magnify the profiles of drying-rate kinetics, which is highly variable among individual vials during the early part of primary drying of a lyophilization cycle. If the cycle was allowed to proceed to completion, then all the vials would be equally dry to a very low level of residual moisture and comparison of the kinetics of drying would not reveal any meaningful differences.

Comparison of process parameters during cycles. The drying-rate studies were conducted in full and partially loaded conditions. Data from these cycles were used for comparison. Under full-load conditions (210 trays), a large amount of solution (~800 kg) is subjected to the lyophilization process. Such a large load of water to be sublimed represents the worst-case scenario in which the aspect ratio of the load versus the condenser capacity was close to 90%, when normally, only 60–70% range is recommended by the equipment manufacturers. Under such conditions, the system capabilities are fully challenged. Hence, the flawless execution of the lyophilization cycles (i.e., maintaining all the independent and dependent parameters within narrow limits) confirms that these units are indeed capable of the performance according to the set parameters and that the profiles generated are comparable to each other.

Materials and methods

Table I: Overview of selected technical characteristics of lyophilizers.
Comparability of relevant technical characteristics of the lyophilizer units. Review of selected technical parameters for the lyophilizer units was performed using installation and operational manuals, as well as installation, operational, and performance qualification test results (see Table I). Those parameters that are generally expected to have the greatest influence on the lyophilization process are indicated as critical; a number of additional characteristics are shown for information purposes only.


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