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Understanding pharmaceutical quality by design
Contributor(s):: Yu, Lawrence X, Amidon, Gregory Khan, Mansoor A Hoag, Stephen W, Polli, James, Raju, G K, Woodcock, Janet
This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and...
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Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development
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...
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The Evolving State of Continuous Processing in Pharmaceutical API Manufacturing: A Survey of Pharmaceutical Companies and Contract Manufacturing Organizations
Contributor(s):: McWilliams, JC, Allian, ADOpalka, SM, May, SA, Journet, M, Braden, TM
This manuscript provides the results of an in-depth survey assessment of the capabilities, experience, and perspectives on continuous processing in the pharmaceutical sector, with respondents from both pharmaceutical companies and Contract Manufacturing Organizations (CMOs). The survey includes...
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Systematic framework for implementation of material traceability into continuous pharmaceutical tablet manufacturing process
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...
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Systematic substrate adoption methodology (SAM) for future flexible, generic pharmaceutical production processes
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...
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Surrogate-based Optimization for Pharmaceutical Manufacturing Processes
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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Residence time distribution modelling and in line monitoring of drug concentration in a tablet press feed frame containing dead zones
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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Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing
Contributor(s):: Esmonde-White, Karen A, Cuellar, Maryann, Uerpmann, Carsten, Lenain, Bruno., Lewis, Ian R.
Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data...
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Progress of Pharmaceutical Continuous Crystallization
Contributor(s):: Zhang, DJ, Xu, SJDu, SC, Wang, JK, Gong, JB
Crystallization is an important unit operation in the pharmaceutical industry. At present, most pharmaceutical crystallization processes are performed in batches. However, due to product variability from batch to batch and to the low productivity of batch crystallization, continuous...
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Process analytical technology in continuous manufacturing of a commercial pharmaceutical product
Contributor(s):: Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo
The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...
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Practical application of roller compaction process modeling
Contributor(s):: Reynolds, Gavin, Ingale, Rohit Roberts, Ron Kothari, Sanjeev, Gururajan, Bindhu
Very limited work has been reported on comparing the performance of the roller compaction process at different scales. The majority of the approaches highlighted in the literature discuss the applicability of using confined uniaxial compaction for predicting the performance of the roller...
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Prediction of segregation tendency occurrence in dry particulate pharmaceutical mixtures: Development of a mathematical tool adapted for granular systems application
Contributor(s):: Abatzoglou, N;, Simard, JS
Segregation phenomena are of importance in nearly all processes involving dry granular and powder mixtures. The extent of segregation directly influences the eventual rejection of a considerable percentage of the final product in the majority of pharmaceutical processes; among these are those...
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Mechanistic modeling for systematic design and analysis of PAT systems
Contributor(s):: Singh, Ravendra, Samad, Noor Asma Fazli Abdul Gernaey, Krist V Woodley, John M, Gani, Rafiqul
Not available
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Method for characterization of loss-in-weight feeder equipment
Contributor(s):: William E. Engisch, Fernando J. Muzzio
This paper presents a method for evaluating the steady state performance of loss-in-weight powder feeding equipment and then demonstrates the use of the method in evaluating the performance of a K-Tron KT35 loss-in-weight feeder for three pharmaceutical grade powders. The method describes in...
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Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing
Contributor(s):: Allenspach, Carl, Timmins, Peter, Lumay, Geoffroy, Holman, James, Minko, Tamara
Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both...
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Implementation of an advanced hybrid MPC–PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plan
Contributor(s):: Singh, Ravendra, Sahay, Abhishek, Karry, Krizia, Muzzio, Fernando, Ierapetritou, Marianthi, Ramachandran, Rohit
It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to...
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Implementation of control system into continuous pharmaceutical manufacturing pilot plant (powder to tablet)
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
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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From form to function: Crystallization of active pharmaceutical ingredients
Contributor(s):: Variankaval, Narayan, Cote, Aaron S., Doherty, Michael F.
In this perspective, we describe the state-of-the-art in API crystal product and process design, highlight barriers that currently prevent the production of better, cheaper crystalline products, and give our best estimate of where the field is going and should go during the next decade.
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Flow Chemistry, Continuous Processing, and Continuous Manufacturing: A Pharmaceutical Perspective
Contributor(s):: May, SA
Flow chemistry has become a vibrant area for Research Article over the past decade. This perspective is intended to capture insights on how these advances have and will continue to impact the development and commercialization of active pharmaceutical ingredients. A series of chemistry examples...
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Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process
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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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...
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Closed-loop feedback control of a continuous pharmaceutical tablet manufacturing process via wet granulation
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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Applications of Flow Chemistry in the Pharmaceutical Industry-Highlights of the Recent Patent Literature
Contributor(s):: Hughes, DL
Flow chemistry is playing an increasingly important role in drug discovery, chemical process development, and manufacturing in the pharmaceutical and agrichemical industries. The current review covers patents and patent applications from 2017 to 1Q 2020 for which no accompanying journal articles...
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Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes
Contributor(s):: Singh, Ravendra, Velazquez, Carlos Sahay, Abhishek Karry, Krizia M Muzzio, Fernando J Ierapetritou, Marianthi G, Ramachandran, Rohit
A novel manufacturing strategy based on continuous processing, integrated with online/inline monitoring tools, coupled with an advanced automatic feedback control system is highly desired for efficient Quality by Design (QbD)-based manufacturing of the next generation of pharmaceutical products...