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

Conclusion

All of the critical hardware and the process control and monitoring mechanisms among the lyophilization units studied were comparable to each other. This similarity supports the hypothesis that the programmable cycle parameters such as shelf temperature, chamber pressure, and time duration of various stages will be executed identically in these units. Even during the early period of drying (when the greatest variability in the sublimation dry rate is expected), the observed rates of sublimation drying were quite close to each other, i.e., 1.79% and 3.21% in fully loaded and partially loaded conditions, respectively. Even under fully loaded conditions and relatively aggressive cycle conditions of the shelf temperature regimen, the lyophilization cycles were executed smoothly as seen by the maintenance of all the independent and dependent parameters (as reflected by the mean product temperatures) within the narrow limits of specifications confirming functional equivalency of these units. In a follow-up study, a set of four commercial large-scale lyophilizers (420-ft2 shelf area) were evaluated for functional equivalency. The validation matrix to use these multiple lyophilizer units for a commercial product was minimized, thereby saving resources and time.

These results provide the basis to establish functional equivalence among different lyophilizers. Once established, functional equivalence can facilitate successful implementation of scale-up and transfer of lyophilization cycles. Such equivalency procedures are desirable in large manufacturing operations, where multiple lyophilizers are used for processing a common lyophilized product, and reduced validation campaigns based upon a matrixing approach can save considerable resources and time.

Amol Mungikar, PhD, is a research investigator; Miron Ludzinski is a senior research scientist, and Madhav Kamat, PhD, RPh,* is a senior principal scientist at Biopharmaceutics R&D, Drug Product Processing and Packaging Technologies, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, NJ 08993,

*To whom all correspondence should be addressed.

Submitted: Mar. 17, 2008. Accepted: Apr. 24, 2009.




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References

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7. FDA, Compliance Program Guidance Manual, 7350.002A: Sterile Drug Inspections (Rockville, MD, 1993).

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10. T.A. Jennings, "Transferring the Lyophilization Process from One Freeze Dryer to Another," Am. Pharm. Rev. 5, 34 (2001).

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