Equipment Capability Measurement of Laboratory Freeze-Dryers: a Comparison of Two Methods

Abstract

The objective of this investigation was to evaluate two methods for measuring the maximum sublimation rate that a freeze-dryer will support—the minimum controllable pressure method and the choke point method. Both methods gave equivalent results, but the minimum controllable pressure method is preferred, since it is easier, faster, and less subjective. The ratio of chamber pressure to condenser pressure corresponding to the onset of choked flow was considerably higher in this investigation (up to about 20:1) than in previously published reports. This ratio was not affected by the location of the pressure gauge on the condenser; that is, on the foreline of the vacuum pump versus on the body of the condenser itself. The total water loss due to sublimation as measured by tunable diode laser absorption spectroscopy was consistently within 5% of gravimetrically determined weight loss, regardless of whether the measurement took place during choked versus non-choked process conditions.

Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update

“…We should mention that one of the important advances in lyophilization process development is an implementation of an instrument that allows direct measurement of sublimation rate (Tunable Diode Laser Absorption Spectroscopy-TDLAS ( [59,82,83]). It may become the cornerstone of our approach to design space development for primary drying by enabling measurement of K v , R p , and equipment capability.…”

“…Then, it is compared to the pressure the freeze-dryer could maintain at a particular sublimation rate (minimum controllable pressure, P min ). Minimum controllable pressure could be obtained by either a sublimation test or by using computational fluid dynamics modeling (CFD) [68,69]. An example of P min as a function of sublimation rate for different freeze-dryers is shown in Fig.…”

Recommended Best Practices in Freeze Dryer Equipment Performance Qualification: 2022

“…The following section contains the recommendations for performing the equipment limit testing. Note that there are differences between the minimum controllable chamber pressure test (described below) and the choked flow test [22], both of which provide the same equipment limit results [35]. Here, we recommend performing the minimum controllable chamber pressure curve test since it is the quicker of the two as described below.…”