In a freeze-drying process (especially during primary drying), product temperature cannot be controlled directly. Thus, it is determined by a combination of process and product parameters. The shelf temperature and chamber pressure are controlled directly based on the user-defined recipe. Indeed, they constitute the main variables for achieving a suitable product temperature over time profile.
Another essential factor with a high impact on product temperature in freeze-drying is the product resistance through the dried layer, Rp, which again depends on the solute concentration, cake thickness, and freezing conditions. High product resistance against the flow of water vapor through the dried layer leads to elevated product temperature and slower drying.
Other parameters influence the product temperature as well, such as the geometry of the container system, the extent of radiative heat transfer to the vials, and the physicochemical state of the product. Due to this multitude of factors, it is very difficult to keep all product units within the batch at a target product temperature throughout the process. This challenge can be overcome by applying Tempris, a process analytical technology capable of real-time temperature monitoring of the product temperature.