PAT for vaccines: the first stage of PAT implementation for development of a well-defined whole-cell vaccine against whooping cough disease.

Since variation in process time and process output is commonly accepted to be inevitable for biological processes, application of Process Analytical Technologies (PAT) on these processes is challenging. In this paper the applicability of PAT on the cultivation of Bordetella pertussis bacteria as part of the manufacture of a vaccine against whooping cough disease is investigated. Scrutinizing and eliminating the most prominent sources of variance make the cultivation process step highly reproducible. Furthermore, the use of DNA microarrays allows investigation of how disturbances influence cellular physiology and product quality. Marker genes for product quality were identified, providing the means to quantitatively assess product quality, which is hardly possible using the mandatory animal tests for product quality. The tools and results described in this paper, combined with suitable on line measurements, can make full PAT application for this process step possible. Ultimately, the process can be designed and controlled towards consistent end product quality.