A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process

09 Jun 2023 | Contributor(s): Singh, Ravendra, Muzzio, Fernando J, Ierapetritou, Marianthi, Ramachandran, Rohit

Continuous pharmaceutical manufacturing together with PAT (Process Analytical Technology) provides a suitable platform for automatic control of the end product quality as desired by QbD (quality by design)-based efficient manufacturing. The precise control of the quality of the pharmaceutical...

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Sen, M, Singh, R, Ramachandran, R

In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and...

A model-based framework for design and analysis of PAT systems

09 Jun 2023 | Workshop | Contributor(s): Gani, Rafiqul, Singh, Ravendra, Gernaey, Krist

A multi-scale hybrid CFD-DEM-PBM description of a fluid-bed granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Barrasso, Dana Singh, Ravendra, Ramachandran, Rohit

In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying...

A retrofit strategy to achieve “Fast, Flexible, Future (F3)” pharmaceutical production processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Rozada-Sanchez, Raquel Wrate, Tim Muller, Frans Gernaey, Krist V Gani, Rafiqul, Woodley, John M

n the work reported here, a substrates adoption methodology for a series of similar substrates has been developed as part of a retrofit strategy. The objective is to achieve “fast, flexible and future” pharmaceutical production processes by adapting a generic modular process-plant template....

A systematic computer aided framework for design and analysis of PAT systems

09 Jun 2023 | Workshop | Contributor(s): Gernaey, Krist, Singh, Ravendra, Gani, Rafiqul

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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 | Peer-reviewed journal | 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...

A Systematic Framework for the Design and Implementation of Sensing and Control Architecture for a Continuous Pharmaceutical Manufacturing Plant

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Muzzio, Fernando J Ierapetritou, Marianthi, Ramachnadran, Rohit

The continuous pharmaceutical manufacture (CPM) plant and control architecture developed earlier is currently being widely implemented in industries [1,2]. CPM indeed provides an appropriate platform to implement suitable monitoring and control architecture, to improve product quality, and to...

A systematic framework to monitor mulling processes using Near Infrared spectroscopy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Wu, Suyang, Panikar, Savitha S Singh, Ravendra Zhang, Jun Glasser, Benjamin, Ramachandran, Rohit

The optimal design of sensor location and setup is essential to ensure the accuracy and precision of in-line process monitoring of water/moisture content. This manuscript presents a systematic framework of using Near Infrared (NIR) spectroscopy to monitor moisture content in an alumina mulling...

A Validated Model for Design and Evaluation of Control Architectures for a Continuous Tablet Compaction Process

09 Jun 2023 | Peer-reviewed journal | 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...

Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes

09 Jun 2023 | Chapter Book | 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...

Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Haas, Nicholas Townsend, Ierapetritou, Marianthi, Singh, Ravendra

In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical tablets can be produced...

An ontological knowledge-based system for the selection of process monitoring and analysis tools

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul

Efficient process monitoring and analysis tools provide the means for automated supervision and control of manufacturing plants and therefore play an important role in plant safety, process control and assurance of end product quality. The availability of a large number of different process...

Application of mechanistic models within a PAT framework

09 Jun 2023 | Website | Contributor(s): Gernaey, Krist, Sin, Gürkan Albo, E Woodley, John Singh, Ravendra, Gani, Rafiqul

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Characterization of NIR interfaces for the feeding and in-line monitoring of a continuous granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Román-Ospino, Andrés D, Tamrakar, Ashutosh Igne, Benoît Dimaso, Elyse Towns Airiau, Christian Clancy, Donald J Pereira, Glinka Muzzio, Fernando J Singh, Ravendra, Ramachandran, Rohit

This work describes the characterization of three NIR interfaces intended to monitor a continuous granulation process. Two interfaces (i.e. a barrel interface and a rotating paddle interface) were evaluated to monitor the API concentration at the entrance of the granulator, and a third interface...

Closed-loop feedback control of a continuous pharmaceutical tablet manufacturing process via wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Barrasso, Dana Chaudhury, Anwesha Sen, Maitraye Ierapetritou, Marianthi Ramachandran, Rohit

The wet granulation route of tablet manufacturing in a pharmaceutical manufacturing process is very common due to its numerous processing advantages such as enhanced powder flow and decreased segregation. However, this route is still operated in batch mode with little (if any) usage of an...

Combined feedforward/feedback control of an integrated continuous granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pereira, Glinka Cathy, Muddu, Shashank Venkat Román-Ospino, Andrés David Clancy, Don Igne, Benoit Airiau, Christian Muzzio, Fernando J Ierapetritou, Marianthi Ramachandran, Rohit, Singh, Ravendra

Continuous manufacturing offers shorter processing times and increased product quality assurance, among several other advantages. This makes it an ever-growing interest among pharmaceutical companies. A suitable efficient control system is however desired for continuous pharmaceutical...

Control of process operations and monitoring of product qualities through generic model-based in batch cooling crystallization

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Samad, Noor Asma Fazli Abdul, Singh, Ravendra Sin, Gürkan Gernaey, Krist V, Gani, Rafiqul

A generic model-based framework has been developed for crystallization processes, with applications aiming at the control of process operations and the monitoring of product quality. This generic model-based framework allows the systematic development of a wide range of crystallization models for...

Design of an Integrated Continuous Manufacturing System

09 Jun 2023 | Chapter Book | Contributor(s): Oka, Sarang S, Escotet-Espinoza, M Sebastian Singh, Ravendra Scicolone, James V Hausner, Douglas B Ierapetritou, Marianthi, Muzzio, Fernando J

This chapter presents a systematic, 12-step approach for designing, implementing, integrating, optimizing, and validating a continuous manufacturing system. Wherever appropriate, it also discusses the regulatory relevance of the technology integration effort. When considering the development of a...

Designing a novel continuous manufacturing plant with superior monitoring and control

09 Jun 2023 | Magazine | Contributor(s): Singh, Ravendra, Zhang, Jun Ierapetritou, Marianthi, Ramachandran, Rohit

There is a growing interest in manufacturing the pharmaceutical product continuously . Along with other advantages , it provides an appropriate platform to implement suitable monitoring and control architecture, to improve the product quality and minimise product rejection and operating expenses....

Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process

09 Jun 2023 | Peer-reviewed journal | 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...

Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Metta, Nirupaplava, Ghijs, Michael Schäfer, Elisabeth Kumar, Ashish Cappuyns, Philippe Van Assche, Ivo Singh, Ravendra Ramachandran, Rohit De Beer, Thomas, Ierapetritou, Marianthi

In view of growing interest and investment in continuous manufacturing, the development and utilization of mathematical model(s) of the manufacturing line is of prime importance. These models are essential for understanding the complex interplay between process-wide critical process parameters...

Effect of material properties on the residence time distribution (RTD) of a tablet press feed frame

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Furukawa, Ryoichi, Singh, Ravendra, Ierapetritou, Marianthi

In continuous manufacturing (CM) of pharmaceutical tablets, the residence time distribution (RTD) of the tablet press feed frame plays an important role in ensuring the critical quality attributes (CQAs) of the final product. Knowledge of factors affecting the RTD of the feed frame is necessary...

Experimental investigation and modelling of tensile strength of pharmaceutical tablets based on shear force applied by feed frame paddles

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Furukawa, Ryoichi, Singh, Ravendra, Ierapetritou, Marianthi

The feed frame is an essential device used in a rotary tablet press and it improves the performance of the powder filling process into dies. However, the feed frame affects critical quality attributes such as a tensile strength and a dissolution negatively due to a shear applied to powders from...

Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Rogers, Amanda Singh, Ravendra Chaudhury, Anwesha John, Joyce Ierapetritou, Marianthi G, Ramachandran, Rohit

In this work, a continuous API purification process has been optimized using an integrated flowsheet model. The simulation is dynamic in nature and includes an API purification step (crystallization), followed by filtration, drying and mixing of the API with an excipient. For the first time, this...