-
Development of a tablet press feed frame lead lag determination model using in-line and off-line NIR measurements
Contributor(s):: Van;Hauwermeiren, D, Peeters, MPeeters, E, Cogoni, G, Yang, LA, De;Beer, T
For continuous pharmaceutical manufacturing of oral solid dosages, it is essential that product quality is measured inline. In this application, a continuous rotary tablet press is used. The goal is a model-based assessment of the quality of the blend in the feed frame to determine whether the...
-
Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame
Contributor(s):: Li, Yi, Anderson, Carl A, Drennen, James K, Airiau, Christian, Igne, Benoît
Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An...
-
Development of an in-line Raman spectroscopic method for continuous API quantification during twin-screw wet granulation
Contributor(s):: Harting Julia, Kleinebudde, Peter
Raman spectroscopy was evaluated as a process analytical technology (PAT) tool for continuous API quantification during twin-screw wet granulation. Therefore, a Raman probe was implemented in front of the granulator barrel. This setup enabled the collection of Raman spectra upon a constant...
-
Development of calibration-free/minimal calibration wavelength selection for iterative optimization technology algorithms toward process analytical technology application
Contributor(s):: Rish, AJJ, Henson, Samuel R., Anik Alam, Md., Liu, Yang, Drennen, James K., Anderson, Carl A
As continuous manufacturing (CM) processes are developed, process analytical technology (PAT) via NIR spectroscopy has become an integral tool in process monitoring. NIR spectroscopy requires the deployment of complex multivariate models to extract the relevant information. The model of choice...
-
Development of Continuous Filtration in a Novel Continuous Filtration Carousel Integrated with Continuous Crystallization
Contributor(s):: Liu, Yiqing C., Domokos, András, Coleman, Simon, Firth, Paul, Nagy, Zoltan K.
Pharmaceutical manufacturing has been largely carried out in batch mode, which has disadvantages such as batch-to-batch variations and difficult scale-up. As a result, the pharmaceutical industry is going through the paradigm shift to continuous manufacturing. Many unit operations have been...
-
Development and Scale-Up of Diversion Strategy for Twin Screw Granulation in Continuous Manufacturing
Contributor(s):: Pawar, Pallavi, Clancy, Don, Gorringe, Lee, Barlow, Steve, Hesketh, Alex, Elkes, Richard
Successful implementation of Continuous Manufacturing technology requires real time product quality monitoring that can result into rejection strategies for material manufactured outside process control limits. In a twin screw granulation process, parameters like water content, powder feed rate,...
-
Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press
Contributor(s):: De Leersnyder, Fien, Peeters, Elisabeth, Djalabi, Hasna, Vanhoorne, Valérie, Van Snick, Bernd, Hong, Ke, Hammond, Stephen, Liu, Angela, Ziemons, Eric, Vervaet, Chris, De Beer, Thomas
A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was...
-
Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process
Contributor(s):: Vanarase, Aditya, Järvinen, Maiju, Paaso, Janne, Muzzio, Fernando
In this paper, a multi-point fiber optic based NIR system was implemented to monitor API concentration at the discharge of a continuous mixer. The sample size being interrogated by NIR was determined by measuring the velocity of the powder on the chute, which allowed selection of the number of...
-
Detailed Analysis of the Online Near-Infrared Spectra of Pharmaceutical Blend in a Rotary Tablet Press Feed Frame
Contributor(s):: Šašić, Slobodan, Blackwood, Daniel, Liu, Angela, Ward, Howard W, Clarke, Hugh
The present study is an in-depth analysis of the online near-infrared (NIR) spectra acquired with a spectrometer mounted on the rotary tablet press feed frame. A 3.5% active pharmaceutical ingredient (API) formulation is analyzed. An attempt is made to determine the API univariately via the 2nd...
-
Determination of Residence Time Distribution in a Continuous Powder Mixing Process With Supervised and Unsupervised Modeling of In-line Near Infrared (NIR) Spectroscopic Data
Contributor(s):: Pedersen, Troels, Karttunen, Anssi-Pekka, Korhonen, Ossi, Wu, Jian Xiong, Naelapää, Kaisa, Skibsted, Erik, Rantanen, Jukka
Successful implementation of continuous manufacturing processes requires robust methods to assess and control product quality in a real-time mode. In this study, the residence time distribution of a continuous powder mixing process was investigated via pulse tracer experiments using near infrared...
-
Development and Application of a Business Case Model for a Stream Sampler in the Pharmaceutical Industry
Contributor(s):: Fontalvo-Lascano, María A, Alvarado-Hernández, Bárbara B., Conde, Carlos, Sánchez, Eric J., Méndez-Piñero, Mayra I., Romañach, Rodolfo
Purpose: A template to prepare a business case for Process Analytical Technology (PAT) and Continuous Manufacturing (CM) projects is presented in this study. Business cases are necessary tools used in different organizations to present new projects for management evaluation. As new ways of...
-
Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit
Contributor(s):: Hou, GY, Power, GBarrett, M, Glennon, B, Morris, G, Zhao, Y
A continuously operated single stage mixed-suspension, mixed-product-removal (MSMPR) crystallizer using intermittent withdrawal via a dip pipe with combined pressure/vacuum was successfully developed for the manufacture of active pharmaceutical ingredients. Approximately 5.8% of the total...
-
Cyber-physical-based PAT (CPbPAT) framework for Pharma 4.0
Contributor(s):: Barenji, Reza Vatankhah, Akdag, Yagmur, Yet, Barbaros., Oner, Levent
Industry 4.0 aims to integrate manufacturing operations into a seamless digital whole by incorporating flexibility, agility, re-configurability, and sustainability. The result of this integration is a “smart factory” that is more lean, agile, and flexible in operations. There are valid reasons,...
-
Data reconciliation in the Quality-by-Design (QbD) implementation of pharmaceutical continuous tablet manufacturing
Contributor(s):: Su, Qinglin, Bommireddy, Yasasvi, Shah Yash, Ganesh, Sudarshan, Moreno, Mariana, Liu, Jianfeng, Gonzalez, Marcial, Yazdanpanah, Nima, O'Connor, Thomas, Reklaitis, Gintaras V., Nagy, Zoltan K
Data provided by in situ sensors is always affected by some level of impreciseness as well as uncertainty in the measurements due to process operation disturbance or material property variance. In-process data precision and reliability should be considered when implementing active product quality...
-
Deep learning for continuous manufacturing of pharmaceutical solid dosage form
Contributor(s):: Roggo, Yves, Jelsch, Morgane, Heger, Philipp, Ensslin, Simon, Krumme, Markus
Continuous Manufacturing (CM) of pharmaceutical drug products is a new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line for production of solid dosage forms was investigated. The line was composed of the subsequent continuous unit:...
-
Deep UV Raman and fluorescence spectroscopy for real-time in situ process monitoring
Contributor(s):: Hug, WF, Nguyen, QReid, M, Sijapati, K, Reid, RD
Raman spectroscopy has become an increasingly common analytical method for real-time, on-line, in-line, and off-line in situ monitoring of product quality in a variety of pharmaceutical, chemical, and biological manufacturing environments, including wastewater quality [1]. The major shortcomings...
-
Design and Commercialization of an End-to-End Continuous Pharmaceutical Production Process: A Pilot Plant Case Study
Contributor(s):: Testa, Christopher J., Hu, Chuntian, Shvedova, Khrystyna, Wu, Wei, Sayin, Ridade, Casati, Federica, Halkude, Bhakti S., Hermant, Paul, Shen, Dongying Erin, Ramnath, Anjana, Su, Qinglin, Born, Stephen C., Takizawa, Bayan, Chattopadhyay, Saptarshi, O'Connor, Thomas F., Yang, Xiaochuan, Ramanujam, Sukumar, Mascia, Salvatore
The pharmaceutical industry faces multiple challenges (e.g., inefficient manufacturing techniques, quality control issues, and supply chain vulnerabilities) because of its current batch-wise approach to manufacturing. Recent regulatory support for continuous manufacturing and advances in...
-
Design of Condition-based Maintenance Framework for Process Operations Management in Pharmaceutical Continuous Manufacturing
Contributor(s):: Ganesh, Sudarshan, Su, Qinglin, Vo, Le Bao Dan, Pepka, Nolan, Rentz, Benjamin, Vann, Lucas, Yazdanpanah, Nima, O'Connor, Thomas, Nagy, Zoltan K., Reklaitis, Gintaras V.
Continuous manufacturing, an emerging technology in the pharmaceutical industry, has the potential to increase the efficiency, and agility of pharmaceutical manufacturing processes. To realize these potential benefits of continuous operations, effectively managing materials, equipment, analyzers,...
-
Designing a novel continuous manufacturing plant with superior monitoring and control
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....
-
Coupling hot melt extrusion and fused deposition modeling: Critical properties for successful performance
Contributor(s):: Bandari, Suresh, Nyavanandi, Dinesha, Dumpa, Nagireddy, Repka, Michael A.
Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be...
-
Control of process operations and monitoring of product qualities through generic model-based in batch cooling crystallization
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...
-
Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors
Contributor(s):: Rehrl, J, Karttunen, APNicolai, N, Hormann, T, Horn, M, Korhonen, O, Nopens, I, De, Beer, T, Khinast, JG
One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the...
-
Control strategy definition for a drug product continuous wet granulation process: Industrial case study
Contributor(s):: Chavez, Pierre-François, Stauffer, Fanny, Eeckman, Frédéric, Bostijn, Nils, Didion, David, Schaefer, Cédric, Yang, Hong, El Aalamat, Yousef, Lories, Xavier, Warman, Martin, Mathieu, Benoit, Mantanus, Jérôme
This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with...
-
Continuous Twin Screw Wet Granulation and Drying - Control Strategy for Drug Product Manufacturing
Contributor(s):: Dahlgren, Gabriella, Tajarobi, Pirjo, Simone, Eric, Ricart, Brendon, Melnick, Jason, Puri, Vibha, Stanton, Courtney, Bajwa, Gurjit
The use of continuous manufacturing has been increasing within the pharmaceutical industry over the last few years. Continuous direct compression has been the focus of publications on the topic to date. The use of wet granulation can improve segregation resistance, uniformity, enhance density,...
-
Continuous, one-step synthesis of pharmaceutical cocrystals via hot melt extrusion from neat to matrix-assisted processing - State of the art
Contributor(s):: Gajda, Maciej, Nartowski, Karol P., Pluta, Janusz, Karolewicz, Bożena
Use of hot melt extrusion (HME) as continuous manufacturing process in the cocrystal synthesis is of increasing interest from both industrial and academic perspective and it is seen as a newly developing branch of mechanochemistry with possible broad application in single step synthesis and...