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Continuous Manufacturing to Improve Pharmaceutical Quality: Research Examples and Opportunities
| Contributor(s):: Geng Tian
Continuous manufacturing (CM) of drug substances and drug productsProcess modeling and simulation (M&S) for CM at FDACM research highlightsOpportunities of CM for generic drug productsPharmaceutical Quality Symposium 2023: Quality, Supply Chain & Advanced Manufacturing -...
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Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms
| Contributor(s):: Wahlich, John
Continuous manufacturing (CM) is defined as a process in which the input material(s) are continuously fed into and transformed, and the processed output materials are continuously removed from the system. CM can be considered as matching the FDA’s so-called ‘Desired State’ of pharmaceutical...
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Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies
| Contributor(s):: Schenck, L, Erdemir, DGorka, LS, Merritt, JM, Marziano, I, Ho, R, Lee, M, Bullard, J, Boukerche, M, Ferguson, S, Florence, AJ, Khan, SA, Sun, CC
Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining...
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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 Tools for Monitoring Pharmaceutical Unit operations: A Control Strategy for Continuous Process Verification
| Contributor(s):: Kim, Eun, Kim, Ji, Kim, Min-Soo, Jeong, Seong, Choi, Du
Various frameworks and methods, such as quality by design (QbD), real time release test (RTRT), and continuous process verification (CPV), have been introduced to improve drug product quality in the pharmaceutical industry. The methods recognize that an appropriate combination of process controls...
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Process Control of Drug Product Continuous Manufacturing Operations - a Study in Operational Simplification and Continuous Improvement
| Contributor(s):: Medendorp, Joseph, Shapally, Sreendhar, Vrieze, Derek, Tolton, Kelly
Purpose The purpose of this manuscript is to demonstrate that implementation of gravimetric measurements provides the same assurance of product quality and process control as spectroscopic measurements (1) for control of drug content in a fixed-dose combination (FDC) tablet and (2) for...
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Part 3: Enhanced Approaches to the Development of the Control Strategy and its Implementation in the Manufacturing Process Description
| Contributor(s):: Popkin, ME, Omer, BASeibert, KD, Luciani, CV, Srivastava, S, Hobson, L, Lepore, JV
A series of case histories from IQ consortium member companies will be presented to exemplify how the application of the ICH Q11 vision for enhanced Quality by Design (QbD) development of the active pharmaceutical ingredient (API) can lead to differentiated outcomes for elements such as the API...
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Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production
| Contributor(s):: Lee, SL, O'Connor, TFYang, XC, Cruz, CN, Chatterjee, S, Madurawe, RD, Moore, CMV, Yu, LX, Woodcock, J
Currently, there is a high level of interest in the pharmaceutical industry in continuous-manufacturing strategies, integrated with online-monitoring tools, that are designed, optimized, and controlled using advanced, model-predictive systems. These strategies can accelerate the full...
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Model predictive control in pharmaceutical continuous manufacturing: A review from a user's perspective
| Contributor(s):: Jelsch, Morgane, Roggo, Yves, Kleinebudde, Peter, Krumme, Markus
Pharmaceutical continuous manufacturing is considered as an emerging technology by the regulatory agencies, which have defined a framework guided by an effective quality risk management. With the understanding of process dynamics and the appropriate control strategy, pharmaceutical continuous...
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Impact of material properties and process variables on the residence time distribution in twin screw feeding equipment
| Contributor(s):: Van Snick, B, Kumar, A, Verstraeten, M, Pandelaere, K, Dhondt, J, Di Pretoro, G, De Beer, T, Vervaet, C, Vanhoorne, V
Screw feeders are integrated as dispensing units in most continuous manufacturing platforms. Hence, characterizing and modelling the residence time distribution (RTD) of materials in feeders is indispensable to understand the traceability of raw materials from the drum till tablet, enabling the...
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Holistic Control Strategies for Continuous Manufacturing
| Contributor(s):: Moore, Christine, Garcia, Thomas, Hausner, Douglas B., Ben-Anat, Inna
Innovative technologies such as continuous manufacturing (CM) bring speed, efficiency, and agility to pharmaceutical manufacturing together with enhanced process robustness and assurance of product quality. During CM, material is simultaneously charged and discharged into process unit operations....
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From powder to tablets: Investigation of residence time distributions in a continuous manufacturing process train as basis for continuous process verification
| Contributor(s):: Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus
The essence of Continuous Manufacturing (CM) resides in the fact that continuous process units are directly connected to each other forming a continuous process train. The thorough understanding of material flow in this train based on suitable sensors, including on-line process analytical...
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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 Use of a Residence Time Distribution (RTD) Model Control Strategy for a Continuous Manufacturing Drug Product Pharmaceutical Process
| Contributor(s):: Hurley, Samantha, Tantuccio, Anthony, Escotet-Espinoza, Manuel Sebastian, Flamm, Matthew, Metzger, Matthew
Residence-time-distribution (RTD)-based models are key to understanding the mixing dynamics of continuous manufacturing systems. Such models can allow for material traceability throughout the process and can provide the ability for removal of non-conforming material from the finished product....
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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...
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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...
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Approach to establishment of control strategy for oral solid dosage forms using continuous manufacturing
| Contributor(s):: Ishimoto, Hayato, Kano, Manabu, Sugiyama, Hirokazu, Takeuchi, Hirofumi, Terada, Katsuhide, Aoyama, Atsushi, Shoda, Takuji, Demizu, Yosuke, Shimamura, Jinen, Yokoyama, Reiji, Miyamoto, Yuji, Hasegawa, Koji, Serizawa, Masaru, Unosawa, Kazuomi, Osaki, Kazuo, Asai, Naochika, Matsuda, Yoshihiro
As a result of the Research Article activities of the Japan Agency for Medical Research Article and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology...
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API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection in cGMP Manufacturing
| Contributor(s):: Johnson, MD, Burcham, CLMay, SA, Calvin, JR, Groh, JM, Myers, SS, Webster, LP, Roberts, JC, Reddy, VR, Luciani, CV, Corrigan, AP, Spencer, RD, Moylan, R, Boyse, R, Murphy, JD, Stout, JR
Crystallization of 204 kg of final active pharmaceutical ingredient was accomplished continuously using a cascade of mixed suspension mixed product removal crystallizers in cGMP manufacturing. This article describes the journey taken to transform a set of technical to final batch crystallizations...
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Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity
| Contributor(s):: Corredor, Claudia, Bu, Xin, McCann, Ryan, Dougherty, Jeffrey, Stevens, Tim, Both, Douglas, Shah, Pankaj
In this work, an example of analytical method quality by design (AQbD) principles applied to an in-line NIR method to monitor blend potency and uniformity in the manufacturing of an oral solid dosage product is presented. An integrated process analytical technology (PAT) method was developed...