In-line control of a freeze-drying process in vials

This article deals with the control of a freeze-drying process in vials. Firstly, the results that can be obtained when the operation is carried out at constant chamber pressure and shelf temperature are predicted by means of mathematical simulations, using a previously validated detailed model, thus allowing off-line optimization of the process. Further improvements can be obtained if the shelf temperature is varied during the process in such a way that the product temperature is always maintained at the maximum allowable value. This strategy for the in-line control of the process allows to minimize the time required for the primary drying, besides satisfying the process constraints. The possibility of manipulating the chamber pressure for control purposes is also discussed. An alternative strategy based on a simple feedback controller, with proportional-integral action, is also investigated: it is able to control the product temperature at a predetermined value, giving stable and fast responses. The controller uses a soft sensor to get a reliable in-line estimate of the controlled variable; i.e., of the maximum temperature of the product.