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, Madhav.firstname.lastname@example.org
*To whom all correspondence should be addressed.
Submitted: Mar. 17, 2008. Accepted: Apr. 24, 2009.
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