Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

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,...

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,...

Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development

09 Jun 2023 | Contributor(s): Ottoboni, S, Coleman, SJSteven, C, Siddique, M, Fraissinet, M, Joannes, M, Laux, A, Barton, A, Firth, P, Price, CJ, Mulheran, PA

Developing a continuous isolation process to produce a pure, dry, free-flowing active pharmaceutical ingredient (API) is the final barrier to the implementation of continuous end-to-end pharmaceutical manufacturing. Recent work has led to the development of continuous filtration and washing...

Thin-Film Evaporator Model for Continuous Active Pharmaceutical Ingredient Manufacturing

09 Jun 2023 | Contributor(s): Lee, BW, Yin, KHSplaine, K, Roesch, B

Thin-film evaporator (TFE) is a popular continuous distillation/evaporation technology for pharmaceutical and fine chemical industries and has several equipment and process configurations that make fundamental modeling approaches very challenging. Specifically, moving wipers and lack of fluid...

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...

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...

Technoeconomic Optimization of Continuous Crystallization for Three Active Pharmaceutical Ingredients: Cyclosporine, Paracetamol, and Aliskiren

09 Jun 2023 | Contributor(s): Diab, S, Gerogiorgis, DI

Mixed suspension, mixed product removal (MSMPR) crystallizers are widely implemented for the continuous crystallization of active pharmaceutical ingredients (APIs), allowing enhanced efficiency, flexibility, and product quality compared to currently dominant batch crystallizer designs....

Technoeconomic Optimization of a Conceptual Flowsheet for Continuous Separation of an Analgaesic Active Pharmaceutical Ingredient (API)

09 Jun 2023 | Contributor(s): Jolliffe, HG, Gerogiorgis, DI

Continuous Pharmaceutical Manufacturing (CPM) has recently emerged as a promising alternative to current batch production methods, which require significant expenditures in order to ensure product quality and process reliability. Advances in new continuous synthesis routes, demonstrations of full...

Systematic Framework for Design and Adaption of Fast, Flexible, Continuous Modular Plants

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

Not available

Systematic framework for implementation of material traceability into continuous pharmaceutical tablet manufacturing process

09 Jun 2023 | Contributor(s): Billups, Matthew, Singh, Ravendra

Purpose: With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing...

Systematic substrate adoption methodology (SAM) for future flexible, generic pharmaceutical production processes

09 Jun 2023 | Contributor(s): Singh, Ravendra, Godfrey, Andy Gregertsen, Björn Muller, Frans Gernaey, Krist V Gani, Rafiqul, Woodley, John M

The discovery of an effective and safe pharmaceutical product is based on success in clinical trials. Often, several candidate compounds targeting the same disease area are tested in order to identify the most efficacious products. This involves the manufacture of small quantities of compounds...

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,...

Systematic computer-aided method and tool (ICAS-PAT) for design, analysis &/or validation of process monitoring and analysis systems (PAT systems)

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

Not available

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...

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...

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...

Regions of attainable particle sizes in continuous and batch crystallization processes

09 Jun 2023 | Contributor(s): Vetter, Thomas, Burcham, Christopher L., Doherty, Michael F.

Process alternatives for continuous crystallization, i.e., cascades of mixed suspension, mixed product removal crystallizers (MSMPRCs) and plug flow crystallizers (PFCs), as well as batch crystallizers are discussed and modeled using population balance equations. The attainable region approach...

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...

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...