Leak Detection and Classification in Pharmaceutical Freeze-Dryers: An Identification-Based Approach

Freeze-drying is a standard procedure in pharmaceutical industry, used to stabilize, store and increase the shelf life of drug products. In this process, the product has to be brought to a very low pressure and the lyophilization chamber has to be perfectly sealed. Even small external leaks can contaminate the entire drug batch. Since a single batch may contain thousands of product vials, freeze-dryer leakages are one of the most critical problems of the entire production chain of lyophilized drugs. We describe a simple mathematical model for lyophilizer leaks and address the problem of identifying and separating internal and external leaks. We propose a leak identification method based on the use of multiple leak detection tests. By using the real data of a pharmaceutical lyophilizer, we show that the proposed method allows to identify internal and external leaks and to estimate their evolution in time.