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,...

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...

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...

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...

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...

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)...

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...

Process Simulation and Control for Continuous Pharmaceutical Manufacturing of Solid Drug Products

09 Jun 2023 | Contributor(s): Ierapetritou, Marianthi, Escotet-Espinoza, M Sebastian, Singh, Ravendra

This chapter focuses on the application and development of unit operation and process models of the major routes of continuous solid dose manufacturing. Process models developed in the chapter are very important tools for the design of control system. The chapter also focuses on the current...

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,...

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...

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...

Model-predictive design, control and optimization of pharmaceutical process

09 Jun 2023 | Contributor(s): Muzzio, F, Singh, R Chaudhury, A Rogers, A Ramachandran, R, Ierapetritou, M

Applying model-predictive methods and a continuous process-control framework to a continuous tablet-manufacturing process. Currently, there is a high level of interest in the pharmaceutical industry in continuous-manufacturing strategies, integrated with online-monitoring tools, that are...

Model-Predictive Design, Control, and Optimization

09 Jun 2023 | Contributor(s): Muzzio, Fernando, Singh, Ravendra Chaudhury, Anwesha Rogers, Amanda Ramachandran, Rohit, Ierapetritou, Marianthi

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....

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...

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...

Mechanistic modeling for systematic design and analysis of PAT systems

09 Jun 2023 | Contributor(s): Singh, Ravendra, Samad, Noor Asma Fazli Abdul Gernaey, Krist V Woodley, John M, Gani, Rafiqul

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Manufacturing of Solid Drug

09 Jun 2023 | Contributor(s): Ierapetritou, Marianthi, Escotet-Espinoza, M Sebastian, Singh, Ravendra

This chapter focuses on the application and development of unit operation and process models of the major routes of continuous solid dose manufacturing. Process models developed in the chapter are very important tools for the design of control system. The chapter also focuses on the current...

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...

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....

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.

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...

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...

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...

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...