Rapid freeze-drying cycle optimization using computer programs developed based on heat and mass transfer models and facilitated by tunable diode laser absorption spectroscopy (TDLAS)

Advances in Process Analytical Technology in Freeze-Drying

“…TDLAS was used to continuously measure the sublimation rate during 5 % mannitol run, and the program was able to quickly perform the calculations based on heat and mass transfer equation. It was demonstrated that maximum product temperatures were controlled slightly below the target temperature, and a cascading temperature-ramping cycle is the most efficient cycle design [10].…”

“…Kuu et al developed computer programs to determine the optimal shelf temperature and chamber pressure while ensuring the product temperature profile is below the target temperature [10]. TDLAS was used to continuously measure the sublimation rate during 5 % mannitol run, and the program was able to quickly perform the calculations based on heat and mass transfer equation.…”

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

“…Mathematical modeling of primary drying has been previously presented [13,19,31,42] and enabled development of a design space as a function of two primary control variables shelf temperature ( T shelf ) and chamber pressure ( P chamber ) with product temperature and primary drying time being the output.…”

“…The use of statistical methods (univariate statistical process control (SPC)-or multivariate statistical process control (MSPC)-based models) has been used to evaluate the process parameters and develop the design space [1]. In addition, there have been great advances in the freeze-drying theory and computational methods, which allow modeling the drying process in vials for a design space construction and avoid many trial-and-error experiments [18,22,38]. Also, scale-up and scale-down models are used towards freeze-drying process optimization, keeping in mind the manufacturing equipment capabilities, towards successful technology transfer, process validation/ qualification batches.…”

Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

“…For example, a spectroscopy based method called tunable diode laser absorption spectroscopy (TDLAS) which allows detection and quantification of trace concentrations of moisture has been introduced for monitoring of freeze-drying cycles into commercial lyophilizers. This technology has been found useful for cycle development as well as scale-up of freeze-drying cycles [8,9]. Another tool is the SMART Freeze dryer developed by FTS systems (Stone Ridge, NY).…”