Lyophilization, or freeze-drying, is a process by which nearly all the water is removed from a frozen product under vacuum by sublimation, causing the ice to change directly from a solid to vapor without passing through a liquid phase.  

Sublimation endpoint determination in Primary Drying is crucial to the development of a robust lyophilization process as it directly impacts the critical quality attributes of the absence of collapse and residual moisture.

Current technologies that determine the endpoint of primary drying include direct product temperature measurement and combining chamber pressure readings of a Capacitance Manometer with a Thermocouple Vacuum Gauge. There is a growing interest in measuring the composition of the atmosphere within the lyophilizer using a Residual Gas Analyzer (RGA), a Process Analytical Technology, to ensure achieving the sublimation endpoint.

During lyophilization, measured process data indicate that the critical process parameters of shelf temperature, chamber pressure and time are within acceptable ranges. Boundary studies are performed with the intent to establish a proven acceptable range for the process.   These studies also demonstrate the robustness of the process by addressing the potential impact of processing deviations that could occur unavoidably, unknowingly or unintentionally, at conditions other than the target parameters, during routine processing.