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Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review
09 Jun 2023 | Contributor(s):: Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi
While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...
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The scope of PAT in real-time advanced control of tablet quality
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit
Continuous pharmaceutical manufacturing together with process analytical technology (PAT) provides a suitable platform for automatic feed-forward/feed-back (FF/FB) control of the end product quality as desired by quality by design (QbD)-based efficient manufacturing. The precise control of the...
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Surrogate-based Optimization for Pharmaceutical Manufacturing Processes
09 Jun 2023 | Contributor(s):: Wang, Zilong, Escotet-Espinoza, M Sebastian Singh, Ravendra, Ierapetritou, Marianthi
The development of pharmaceutical manufacturing processes has been facilitated by recent advances in the process simulation area. However, since the simulations are usually complex and the analytical expressions of the model can be unknown, it is difficult to directly apply traditional...
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Simulation-Based Design of an Efficient Control System for the Continuous Purification and Processing of Active Pharmaceutical Ingredients
09 Jun 2023 | Contributor(s):: Sen, M, Singh, R, Ramachandran, R
In this study, an efficient system-wide controlsystem has been designed for the integrated continuous purification and processing of the active pharmaceutical ingredient (API). The control strategy is based on the regulatory PID controller which is most widely used in the manufacturing industry...
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Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies
09 Jun 2023 | Contributor(s):: Chopda, Viki, Gyorgypal, Aron Yang, Ou Singh, Ravendra Ramachandran, Rohit Zhang, Haoran Tsilomelekis, George Chundawat, Shishir PS, Ierapetritou, Marianthi G
Continuous bioprocessing is significantly changing the biological drugs (or biologics) manufacturing landscape by potentially improving product quality, process stability, and overall profitability, as was similarly seen during the adoption of advanced manufacturing processes for small molecule...
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Residence Time Distribution as a Traceability Method for Lot Changes in A Pharmaceutical Continuous Manufacturing System
09 Jun 2023 | Contributor(s):: Sánchez-Paternina, Adriluz, Martínez-Cartagena, Pedro Li, Jingzhe Scicolone, James Singh, Ravendra Lugo, Yleana C Romañach, Rodolfo J Muzzio, Fernando J, Román-Ospino, Andrés D
Residence time distribution (RTD) models were developed to track raw material lots and investigate batch transitions in a continuous manufacturing system. Two raw materials with similar physical properties (granular metformin and lactose) were identified via Principal Component Analysis (PCA)...
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Residence time distribution modelling and in line monitoring of drug concentration in a tablet press feed frame containing dead zones
09 Jun 2023 | Contributor(s):: Tanimura, Shinji, Singh, Ravendra Román-Ospino, Andrés D, Ierapetritou, Marianthi
The presence of a ‘significant dead zone’ in any continuous manufacturing equipment may affect the product quality and need to be investigated systematically. Dead zone will affect the residence time distribution (RTD) of continuous manufacturing and thus the mixing and product quality. Tablet...
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Process dynamics and control of API manufacturing and purification processes
09 Jun 2023 | Contributor(s):: Sen, Maitraye, Singh, Ravendra, Ramachandran, Rohit
The pharmaceutical industries have started transitioning toward continuous mode of manufacturing recently. Due to many advantages of the continuous manufacturing over the traditional alternatives, the industries are putting huge effort to efficiently adapt the continuous processing mode. However,...
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Pharmaceutical Cocrystal Drug Products: An Outlook on Product Development
09 Jun 2023 | Contributor(s):: Shaikh, Rahamatullah, Singh, Ravendra Walker, Gavin M, Croker, Denise M
Active pharmaceutical ingredients (APIs) are most commonly formulated and delivered to patients in the solid state. Recently, an alternative API solid-state form, namely the pharmaceutical cocrystal, has witnessed increasing academic and industrial interest due to its potential to deliver bespoke...
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PAT for pharmaceutical manufacturing process involving solid dosages forms
09 Jun 2023 | Contributor(s):: Román-Ospino, Andrés D, Cárdenas, Vanessa Ortega-Zuñiga, Carlos, Singh, Ravendra
This chapter summarizes important considerations to develop multivariate methods for pharmaceuticals process monitoring and quality control in solid dosages forms based on spectroscopic techniques. The stages described in each section aimed to explain relevant knowledge of the calibration...
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Model-based computer-aided framework for design of process monitoring and analysis systems
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul
In the manufacturing industry, for example, the pharmaceutical industry, a thorough understanding of the process is necessary in addition to a properly designed monitoring and analysis system (PAT system) to consistently obtain the desired end-product properties....
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Modeling the effects of material properties on tablet compaction: A building block for controlling both batch and continuous pharmaceutical manufacturing processes
09 Jun 2023 | Contributor(s):: Escotet-Espinoza, M Sebastian, Vadodaria, Shishir Singh, Ravendra Muzzio, Fernando J, Ierapetritou, Marianthi G
As the pharmaceutical industry modernizes its manufacturing practices and incorporates more efficient processing approaches, it is important to reevaluate which process design elements affect product quality and the means to study these systems. The purpose of this work is to provide insight on a...
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Model development and prediction of particle size distribution, density and friability of a comilling operation in a continuous pharmaceutical manufacturing process
09 Jun 2023 | Contributor(s):: Metta, Nirupaplava, Verstraeten, Maxim Ghijs, Michael Kumar, Ashish Schafer, Elisabeth Singh, Ravendra De Beer, Thomas Nopens, Ingmar Cappuyns, Philippe, Van Assche, Ivo
The comilling process plays an important role in solid oral dosage manufacturing. In this process, the granulated products are comminuted to the required size distribution through collisions created from a rotating impeller. In addition to predicting particle size distribution, there is a need to...
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Integrated moving horizon-based dynamic real-time optimization and hybrid MPC-PID control of a direct compaction continuous tablet manufacturing process
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Sen, Maitraye Ierapetritou, Marianthi, Ramachandran, Rohit
In this manuscript, a moving horizon-based real-time optimization (MH-RTO) has been integrated with a hybrid model predictive control (MPC) system for a continuous tablet manufacturing process for quality by design (QbD)-based efficient continuous manufacturing. In the proposed approach, the...
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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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ICAS-PAT: A software for design, analysis and validation of PAT systems
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul
In chemicals based product manufacturing, as in pharmaceutical, food and agrochemical industries, efficient and consistent process monitoring and analysis systems (PAT systems) have a very important role. These PAT systems ensure that the chemicals based product is manufactured with the specified...
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Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation
09 Jun 2023 | 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...
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Experimental investigation and modelling of tensile strength of pharmaceutical tablets based on shear force applied by feed frame paddles
09 Jun 2023 | 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...
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Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route
09 Jun 2023 | 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...
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Effect of material properties on the residence time distribution (RTD) of a tablet press feed frame
09 Jun 2023 | 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...
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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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Control of process operations and monitoring of product qualities through generic model-based in batch cooling crystallization
09 Jun 2023 | 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...
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Closed-loop feedback control of a continuous pharmaceutical tablet manufacturing process via wet granulation
09 Jun 2023 | 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...
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Combined feedforward/feedback control of an integrated continuous granulation process
09 Jun 2023 | 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...