Thomas de Beer
Prof. Thomas De Beer graduated in pharmaceutical sciences in 2002 at the Ghent University in Belgium. He obtained his PhD at the same university in 2007. For his PhD research, he worked three months at University of Copenhagen in Denmark (Prof. J. Rantanen). After his PhD, he was a FWO funded post-doctoral fellow at the Ghent University (2007-2010). Within his post-doc mandate, he worked 8 months at the Ludwig-Maximilians-University in Munich, Germany (Prof. Winter and Prof. Friess). In February 2010, he became professor in Process Analytical Technology at the Faculty of Pharmaceutical Sciences of the Ghent University. His research goals include the implementation of PAT systems in innovative pharmaceutical production processes.
In-depth analysis of multiple logged process parameters during a continuous granulation and drying process
Jurgen Vercruysse1, Margot Fonteyne2, , U. Delaet3, I. Van Assche3, Jean Paul Remon1, Chris Vervaet1, Thomas De Beer2
1Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
2Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
3Department of Pharmaceutical Development, Johnson&Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Beerse, Belgium
Continuous production is expected to make an impact on the manufacturing of solid dosage forms as there are many advantages associated with this mode of manufacturing which are all related to important economic drivers for change (i.e. quality, cost and time). As wet granulation is the most popular method to improve material properties (flow, homogeneity, compressibility) prior to tabletting, it is obvious that a continuous wet granulation process is of high importance for a manufacturer of solid dosage forms. Furthermore, a fully continuous manufacturing process requires continuous monitoring of critical process parameters as well as continuous inspection of product quality attributes.
In the present study, three similar long (10 hours each) continuous manufacturing runs of a pharmaceutical formulation were performed using the ConsiGmaTM-25 system (GEA Pharma Systems, ColletteTM, Wommelgem, Belgium), which is a fully continuous from powder to tablet manufacturing line. During processing, the ConsiGma TM-25 system continuously logged 55 different process parameters, hence supplying a huge amount of data.
Several multivariate data-analysis and time series analysis techniques were applied to extract relevant process information from the data-sets generated during the three performed 10 hour manufacturing runs. Numerous process phenomena and process trends could be identified and correlations between the different consecutive continuous units of the ConsiGmaTM-25 could be elucidated, which is essential for the development of feedforward control systems. Furthermore, some important uncontrolled process phenomena were detected (e.g., gradual stoppage of the filter bags in the six-segmented dryer during processing, hence gradually influencing the drying process performance). These observations allowed to develop solutions to overcome such undesired and uncontrolled process disturbances in the future. Finally, it was evaluated which critical process parameters are not assessed by the ConsiGma TM-25 automatically logged data. Based on this, suggestions are made to implement appropriate process sensors allowing to monitor the remaining uncontrolled critical process parameters in real-time.