Niels Nicolai

PhD Student

Prof. dr. ir. Ingmar Nopens - Ghent University
Prof. dr. Thomas De Beer - Laboratory of Pharmaceutical Process Analytical Technology, Ghent University
Prof. dr. ir Krist V. Gernaey- Department of Chemical and Biochemical Engineering, Technical University of Denmark

Research background

Traditionally, production of pharmaceuticals is realized using batch processing steps which can be fairly inefficient, time-consuming and poorly upscalable. Recent clarification by the regulatory authorities as well as the industry have accelerated the search for new manufacturing technologies. Consequently, a transition towards continuous manufacturing which includes real-time process monitoring and closed-loop control, has gained tremendous attention over the past few years. This because of the economic, environmental, safety and product-related advantages of a continuous manufacturing line. Driven by this change in mind-set, an innovative continuous from powder-to-tablet line (ConsiGmaTM-25, ColletteTM, GEA Pharma Systems) was developed for secondary manufacturing of pharmaceutical tablets.

Research objective

Previous and current studies at this research group are mainly focusing on the development of advanced measurement tools, which allow for real-time monitoring, and first principle models to ensure an improved understanding of the different phenomena occurring during processing. Based on this knowledge closed-loop control strategies for the ConsiGma-25 wet granulation system will be implemented to maintain final and intermediate critical quality attributes within the desired specifications.

Research methodology
  1. In a first step, different supervisory control strategies will be virtually developed using experimentally validated mechanistic models and/or empirical black-box models of the unit operations.
  2. For each unit process the developed controller will be implemented and validated on the ConsiGma using the Siemens SIPAT platform.
  3. Next, system-wide supervisory control strategies, i.e. coupling the different unit operations, will be established using an integrated process model.
  4. Finally, the system-wide controller will be implemented in the available SCADA system of the ConsiGma.
Key publications
Nicolaï, N., De Leersnyder, F., Copot, D., Stock, M., Ionescu, C. M., Gernaey, K. V., Nopens, I. and De Beer, T. (2018), Liquid-to-solid ratio control as an advanced process control solution for continuous twin-screw wet granulation, AIChE Journal doi:10.1002/aic.16161
Nicolaï, N., Verstraeten, M., Nopens, I., De Beer, T. (2018), Process control levels for continuous pharmaceutical tablet manufacturing, in Chemical Engineering in the Pharmaceutical Industry, Second Edition - Drug Product, John Wiley & Sons Inc., doi:10.1002/aic.16161
Rehrl, J., Karttunen, A.P., Nicolaï, N., Hörmann, T., Horn, M., Korhonen, O., Nopens, I., De Beer, T., Khinast, J.G. (2018) Control of Three Different Continuous Pharmaceutical Manufacturing Processes: Use of Soft Sensors, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2018.03.027