Representative Scale-Down Lyophilization Cycle Development Using a Seven-Vial Freeze-Dryer (MicroFD).

We have implemented the use of a small-scale, 7-vial Micro Freeze Dryer (MicroFD; Millrock Technology, Inc.) that has the capability to accurately control heat transfer during lyophilization. We demonstrate the ability to fine-tune the MicroFD vial heat transfer coefficient (K) to match the K of vials in a LyoStar III laboratory-scale unit. When the MicroFD is run under conditions that match the K of the LyoStar III, the resulting lyophilization performance between scales results in equivalent product temperature profiles and critical quality attributes for the same drying process. The proposed workflow demonstrates how exploitation of K control in the MicroFD enables cycle development of at-scale lyophilization processes using only 7 product vials. By changing the MicroFDK, laboratory and, potentially, manufacturing cycles may be simulated using only 7 product vials for tremendous active pharmaceutical ingredient savings, as long as at-scale heat transfer coefficients are well characterized.