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 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 comparative review of multi-rate moving horizon estimation schemes for bioprocess applications

09 Jun 2023 | Contributor(s): Elsheikh, Mohamed, Hille, Rubin Tatulea-Codrean, Alexandru, Kramer, Stefan

Advanced control and monitoring of bioprocesses are dependent on accurate state and parameter information. At the same time, bioprocesses are well known for their time-varying behavior and difficulty of obtaining online measurements of the important process states. The selection and the tuning of...

A Continuous Operation Concept for a Rotary Tablet Press Using Mass Flow Operating Points

09 Jun 2023 | Contributor(s): Martinetz, Michael Christian, Rehrl, Jakob Aigner, Isabella Sacher, Stephan, Khinast, Johannes

Abstract In a continuous pharmaceutical manufacturing line the rotary tablet press was viewed as the master of control concept and defined the mass flow through the entire process. According to a conventional control concept, missing mass flow from an upstream unit operation leads to a shutdown...

A design aid for crystal growth engineering

09 Jun 2023 | Contributor(s): Li, Jinjin, Tilbury, Carl J. Kim, Seung Ha, Doherty, Michael F.

With the highly competitive development of chemical and pharmaceutical industries, mastering crystal growth is becoming increasingly necessary. Modern industrial manufacturers place high importance on the ability to grow crystals with a specific habit using tailored operating conditions. A...

A Digital Twin for Process Optimisation in Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Gerogiorgis, Dimitrios I., Castro-Rodriguez, Daniel

Organic synthesis is a critical step in producing any Active Pharmaceutical Ingredient (API): it encompasses a series of organic (mostly catalytic) reactions and separations, whose purpose is to arrive at a solution of a target molecule, which must then undergo crystallisation for purification,...

A fast moving horizon estimation algorithm based on nonlinear programming sensitivity

09 Jun 2023 | Contributor(s): Zavala, Victor M, Laird, Carl D, Biegler, Lorenz T

Moving horizon estimation (MHE) is an efficient optimization-based strategy for state estimation. Despite the attractiveness of this method, its application in industrial settings has been rather limited. This has been mainly due to the difficulty to solve, in real-time, the associated dynamic...

A fast moving horizon estimation algorithm based on nonlinear programming sensitivity

09 Jun 2023 | Contributor(s): Zavala, Victor M, Laird, Carl D, Biegler, Lorenz T

Moving horizon estimation (MHE) is an efficient optimization-based strategy for state estimation. Despite the attractiveness of this method, its application in industrial settings has been rather limited. This has been mainly due to the difficulty to solve, in real-time, the associated dynamic...

A flowsheet model for the development of a continuous process for pharmaceutical tablets: An industrial perspective

09 Jun 2023 | Contributor(s): Garcia-Munoz, Salvador, Butterbaugh, Adam Leavesley, Ian Manley, Leo Francis, Slade, David, Bermingham, Sean

A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of...

A framework for model reliability and estimability analysis of crystallization processes with multi-impurity multi-dimensional population balance models

09 Jun 2023 | Contributor(s): Fysikopoulos, D, Benyahia, B Borsos, A Nagy, Z K, Rielly, C D

The development of reliable mathematical models for crystallization processes may be very challenging due the complexity of the underlying phenomena, the inherent Population Balance Models (PBMs) and the large number of parameters that need to be identified from experimental data. Due to the poor...

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 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 hybrid neural network-first principles approach to process modeling

09 Jun 2023 | Contributor(s): Psichogios, Dimitris C., Ungar, Lyle H.

A hybrid neural network‐first principles modeling scheme is developed and used to model a fedbatch bioreactor. The hybrid model combines a partial first principles model, which incorporates the available prior knowledge about the process being modeled, with a neural network which...

A hybrid neural network-first principles approach to process modeling

09 Jun 2023 | Contributor(s): Psichogios, Dimitris C., Ungar, Lyle H.

A hybrid neural network‐first principles modeling scheme is developed and used to model a fedbatch bioreactor. The hybrid model combines a partial first principles model, which incorporates the available prior knowledge about the process being modeled, with a neural network which...

A hybrid NIR-soft sensor method for real time in-process control during continuous direct compression manufacturing operations

09 Jun 2023 | Contributor(s): Cogoni, Giuseppe, Husain, Anas, Alam, Md Anik, Liu, Yang Angela, Kamyar, Reza

Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet...

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

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

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

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

A Moving Horizon Estimator for processes with multi-rate measurements: A Nonlinear Programming sensitivity approach

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Lopez-Negrete, Rodrigo, Biegler, Lorenz T.

Moving Horizon Estimation (MHE) provides a framework that allows one to incorporate both frequent and infrequent observations easily because it uses a window of past measurements, where the slower ones can be introduced as they become available. Also, MHE allows for the use of constraints on the...

A Moving Horizon-Based Approach for Least-Squares Estimation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Robertson, Douglas G., Lee, Jay H., Rawlings, James B.

A general formulation of the moving horizon estimator is presented. An algorithm with a fixed-size estimation window and constraints on states, disturbances, and measurement noise is developed, and a probabilistic interpretation is given. The moving horizon formulation requires only one more...

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 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 New Software Framework for Implementing Crystal Growth Models to Materials of Any Crystallographic Complexity

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Zhao, Yongsheng, Tilbury, Carl J. Landis, Steven Sun, Yuanyuan, Li, Jinjin, Zhu, Peng, Doherty, Michael F.

To continue the realization of new therapeutics, a more diverse range of solid forms is being considered. Synthetic modalities are broadening beyond simple organic molecules to more complicated structures, including organic salts, cocrystals, and solvates. As in all crystalline applications,...

A Novel Integrated Workflow for Isolation Solvent Selection Using Prediction and Modeling

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ottoboni, S, Wareham, BVassileiou, A, Robertson, M, Brown, CJ, Johnston, B, Price, CJ

A predictive tool was developed to aid process design and to rationally select optimal solvents for isolation of active pharmaceutical ingredients. The objective was to minimize the experimental work required to design a purification process by (i) starting from a rationally selected...

A novel robust digital design of a network of industrial continuous cooling crystallizers of dextrose monohydrate: From laboratory experiments to industrial application

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nagy, Zoltan K., Szilagyi, Botond Pal, Kanjakha, Tabar, Iman Beheshti ;

This paper presents the first-ever industrial application of the digital design of a complex, large-scale industrial continuous crystallization network. The aim of the work is to optimize a large-scale continuous crystallization network used for the purification of dextrose monohydrate, by...

A perspective on Quality-by-Control (QbC) in pharmaceutical continuous manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Su, Qinglin, Ganesh, Sudarshan Moreno, Mariana Bommireddy, Yasasvi, Gonzalez, Marcial, Reklaitis, Gintaras V., Nagy, Zoltan K.

The Quality-by-Design (QbD) guidance issued by the US Food and Drug Administration (FDA) has catalyzed the modernization of pharmaceutical manufacturing practices including the adoption of continuous manufacturing. Active process control was highlighted recently as a means to improve the QbD...