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Towards a novel continuous HME-Tableting line: Process development and control concept
09 Jun 2023 | Contributor(s):: Sacher, Stephan, Celikovic, Selma, Rehrl, Jakob, Poms, Johannes, Kirchengast, Martin, Kruisz, Julia, Sipek, Martin, Salar-Behzadi, Sharareh, Berger, Hannes, Stark, Gerald, Horn, Martin, Khinast, Johannes G.
The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous...
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System-wide hybrid MPC–PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit
The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables,...
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Real-time feasible model-based crystal size and shape control of crystallization processes
09 Jun 2023 | Contributor(s):: Szilagyi, Botond, Nagy, Zoltan K.
The simultaneous control of crystal size and shape is particularly important in fine chemical and pharmaceutical crystallization. These two quantities influence the dissolution rate and bioavailability of final drug products, and also contribute to the manufacturability and efficiency of...
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PAT implementation for advanced process control in solid dosage manufacturing - A practical guide
09 Jun 2023 | Contributor(s):: Sacher, Stephan, Poms, Johannes, Rehrl, Jakob, Khinast, Johannes G.
The implementation of continuous pharmaceutical manufacturing requires advanced control strategies rather than traditional end product testing or an operation within a small range of controlled parameters. A high level of automation based on process models and hierarchical control concepts is...
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Optimized continuous pharmaceutical manufacturing via model-predictive control
09 Jun 2023 | Contributor(s):: Rehrl, Jakob, Kruisz, Julia, Sacher, Stephan, Khinast, Johannes, Horn, Martin
This paper demonstrates the application of model-predictive control to a feeding blending unit used in continuous pharmaceutical manufacturing. The goal of this contribution is, on the one hand, to highlight the advantages of the proposed concept compared to conventional PI-controllers, and, on...
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Model predictive control in pharmaceutical continuous manufacturing: A review from a user's perspective
09 Jun 2023 | Contributor(s):: Jelsch, Morgane, Roggo, Yves, Kleinebudde, Peter, Krumme, Markus
Pharmaceutical continuous manufacturing is considered as an emerging technology by the regulatory agencies, which have defined a framework guided by an effective quality risk management. With the understanding of process dynamics and the appropriate control strategy, pharmaceutical continuous...
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Mechanistic modeling and parameter-adaptive nonlinear model predictive control of a microbioreactor
09 Jun 2023 | Contributor(s):: Hong, Moo Sun, Braatz, Richard D.
Microbioreactors are a promising technology to accelerate biologic drug development. In aerobic cellular respiration, a potential limit to the productivity of such systems is the transport of oxygen from an external gas to the most oxygen-deficient cells, and the potential for excessive spatially...
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Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC
09 Jun 2023 | Contributor(s):: Rehrl, J, Kirchengast, MCelikovic, S, Sacher, S, Kruisz, J, Khinast, J, Horn, M
Purpose The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletization process. The new concept should improve the particle size distribution of the pellets produced. Methods Production of pellets containing an active pharmaceutical...
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Implementation of an advanced hybrid MPC–PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plan
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Sahay, Abhishek, Karry, Krizia, Muzzio, Fernando, Ierapetritou, Marianthi, Ramachandran, Rohit
It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to...
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Implementation of control system into continuous pharmaceutical manufacturing pilot plant (powder to tablet)
09 Jun 2023 | Contributor(s):: Singh, Ravendra
Real-time process control is highly desired for efficient quality by design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end-product quality, satisfies the high regulatory constraints, facilitates real-time release of the product, and optimizes the resources....
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Hybrid advanced control of flexible multipurpose continuous tablet manufacturing process via direct compaction
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit
With numerous case studies throughout, this valuable guide is ideal for those engaged in, or learning about, continuous processing in pharmaceutical manufacturing.
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Ensuring tablet quality via model-based control of a continuous direct compaction process
09 Jun 2023 | Contributor(s):: Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M
Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...
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Evaluation of a Combined MHE-NMPC Approach to Handle Plant-Model Mismatch in a Rotary Tablet Press
09 Jun 2023 | Contributor(s):: Huang, Yan-Shu, Reklaitis, Gintaras V.
The transition from batch to continuous processes in the pharmaceutical industry has been driven by the potential improvement in process controllability, product quality homogeneity, and reduction of material inventory. A quality-by-control (QbC) approach has been implemented in a variety of...
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Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process
09 Jun 2023 | Contributor(s):: Bhaskar, Aparajith, Barros, Fernando N, Singh, Ravendra
In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the...
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Automated and continuous synthesis of drug substances
09 Jun 2023 | Contributor(s):: Sacher, Stephan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D, Kirschneck, Dirk, Kappea, C. Oliver, Horn, Martin
A continuous synthesis line was developed integrating different common reaction stepsnamely nitration, substitution and hydrogenation. Mesalazine as model drug substancewas produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PATstrategy was implemented to equip the full...
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Artificial neural network modelling of continuous wet granulation using a twin-screw extruder
09 Jun 2023 | Contributor(s):: Shirazian, Saeed, Kuhs, Manuel, Darwish, Shaza, Croker, Denise., Walker, Gavin M
Computational modelling of twin-screw granulation was conducted by using an artificial neural network (ANN) approach. Various ANN configurations were considered with changing hidden layers, nodes and activation functions to determine the optimum model for the prediction of the process. The neural...
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Advanced control of a continuous oscillatory flow crystalliser
09 Jun 2023 | Contributor(s):: Tahir, F, Krzemieniewska-Nandwani, KMack, J, Lovett, D, Siddique, H, Mabbott, F, Raval, V, Houson, I, Florence, A
This paper presents the application and challenges of achieving Model Predictive Control (MPC) on two continuous oscillatory baffled crystallisation reactors, delivering precise product quality control in the face of raw material fluctuations. A key advantage of MPC is that it effectively deals...
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Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Velazquez, Carlos Sahay, Abhishek Karry, Krizia M Muzzio, Fernando J Ierapetritou, Marianthi G, Ramachandran, Rohit
A novel manufacturing strategy based on continuous processing, integrated with online/inline monitoring tools, coupled with an advanced automatic feedback control system is highly desired for efficient Quality by Design (QbD)-based manufacturing of the next generation of pharmaceutical products...
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A Validated Model for Design and Evaluation of Control Architectures for a Continuous Tablet Compaction Process
09 Jun 2023 | Contributor(s):: Nunes de Barros, Fernando, Bhaskar, Aparajith, Singh, Ravendra
The systematic design of an advanced and efficient control strategy for controlling critical quality attributes of the tablet compaction operation is necessary to increase the robustness of a continuous pharmaceutical manufacturing process and for real time release. A process model plays a very...
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A systematic framework for onsite design and implementation of a control system in a continuous tablet manufacturing process
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Sahay, Abhishek Muzzio, Fernando Ierapetritou, Marianthi, Ramachandran, Rohit
A novel manufacturing strategy based on continuous processing integrated with online/inline monitoring tools coupled with an advanced control system is highly desired for efficient Quality by Design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end product...