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Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing
| Contributor(s):: Sara Fathollahi, Pauline H. M. Janssen, Bastiaan H. J. Dickhoff, Henderik W. Frijlink
The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of...
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Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant
| Contributor(s):: Johannes Khinast, Martin Horn, Jakob Rehrl, Selma Celikovic, Johannes Poms
ConsiGmaTM-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw...
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Implementation of a fully integrated continuous manufacturing line for direct compression and coating at a commercial pharmaceutical facility – Part 1: Operational considerations and control strategy
| Contributor(s):: Conway, Stephen L., Rosas, Juan G., Overton, Paul, Tugby, Neil, Cryan, Phillip, Witulski, Frank, Hurley, Samantha, Wareham, Laura, Tantuccio, Anthony, Ramasamy, Manoharan, Lalloo, Anita, Gibbs, Mason, Meyer, Robert F.
We implement a fully integrated continuous manufacturing (CM) line for direct compression and coating of a pharmaceutical oral solid dosage form in a commercial production facility. In this first paper of a two-part series, we describe process design and operational choices made to introduce CM...
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Implementation of a fully integrated CM direct compression and coating process at a commercial pharmaceutical facility - Part 2: PAT and RTD results for normal operational conditions batches.
| Contributor(s):: Rosas, JG, Brush, P, Thompson, B, Miller, C, Overton, P, Tugby, N, Stoliarskaia, D, Hurley, S, Ramasamy, M, Conway, SL
This is the second of two articles detailing the continuous manufacturing (CM) development and implementation activities for an marketed product which have been realized in novel, qualified equipment, using validated control strategy elements to enable manufacture of batches under current good...
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Embracing continuous manufacturing in the pharmaceutical industry
| Contributor(s):: Joelle Anselmo
"Drugmakers have been slow to adopt the production process, which experts say can streamline operations, boost data quality and reduce time to market."
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MOOC 1 Introduction to Continuous Manufacturing
| Contributor(s):: RCPE
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MOOC I - Batch vs. Continuous Manufacturing: Revolutionizing Medicine Production
| Contributor(s):: RCPE
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MOOC I Introduction - The Advantages and Challenges of Continuous Manufacturing in Pharmaceuticals
| Contributor(s):: RCPE
In this video, we start exploring the world of continuous manufacturing in the pharmaceutical industry. Discover how this innovative technology is revolutionizing the production of medicines, its advantages over traditional batch manufacturing, and the challenges it presents. Join us as we delve...
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CDER's Emerging Technology Program
| Contributor(s):: Thomas O’Connor
Emerging Technology Program (ETP) OverviewETP TrendsLifecycle of an Emerging TechnologyInteracting with the ETPPharmaceutical Quality Symposium 2023: Quality, Supply Chain & Advanced Manufacturing - 10/31/2023 | FDA
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Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process
| Contributor(s):: Gerald A. Hebbink, Pauline H. M. Janssen, Jurjen H. Kok, Lorenzo Menarini, Federica Giatti, Caterina Funaro, Salvatore Fabrizio Consoli, Bastiaan H. J. Dickhoff
Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and...
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A Comparative Investment Analysis of Batch Versus Continuous Pharmaceutical Manufacturing Technologies
| Contributor(s):: Clifford V. Rossi
Purpose This study examines the risks and economics associated with investing in continuous (CM) versus conventional batch manufacturing for production of oral solid dosage pharmaceutical (OSD) products in the USA and abroad. Methods A stochastic net present value (NPV) simulation of brand...
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Addressing Barriers in Implementing Pharmaceutical Continuous Manufacturing Key Concepts & Challenges in Pharmaceutical Continuous Manufacturing
| Contributor(s):: Gabriela Grasa Mannino
Pharmaceutical continuous manufacturing (PCM) can reduce production time, decrease labor costs, and optimize process flow and the supply chain. Although some industry leaders have already invested in PCM, its widespread implementation has yet to be achieved. Major challenges to adoption include...
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Effect of batch-to-batch variation of spray dried lactose on the performance of feeders
| Contributor(s):: Carlota Mendez Torrecillas, Florian Tegel, Ralf Weinekötter, Bernhard Meir, Bastiaan H.J. Dickhoff, Sri Sharath Kulkarni, Pauline H.M. Janssen
With the emergence of quality by design (QbD), it becomes imperative to gain understanding of the impact of batch-to-batch variability of raw materials on the performance of processes. Feeding is the first unit of operation in a continuous manufacturing line and is critical for the final product...
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Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen
| Contributor(s):: Clive Badman, Charles L.Cooney, Alastair Florence, Konstantin Konstantinov, Markus Krumme, Salvatore Mascia, Moheb Nasr, Bernhardt L. Trout
We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.
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Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: Influence of mass flow and rotation speed variations
| Contributor(s):: Martínez, Lizbeth, Peinado, Antonio, Liesum, Lorenz, Betz, Gabriele
The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic...
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Use of the channel fill level in defining a design space for twin screw wet granulation
| Contributor(s):: Gorringe, L. J., Kee, G. S., Saleh, M. F., Fa, N. H., Elkes, R. G.
Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous Research Article has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the...
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TPLS as predictive platform for twin-screw wet granulation process and formulation development
| Contributor(s):: Ryckaert, A., Van Hauwermeiren, D., Dhondt, J., De Man, A., Funke, A., Djuric, D., Vervaet, C., Nopens, I., De Beer, T.
In recent years, the interest in continuous manufacturing techniques, such as twin-screw wet granulation, has increased. However, the understanding of the influence of the combination of raw material properties and process settings upon the granule quality attributes is still limited. In this...
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Tracking raw material flow through a continuous direct compression line. Part II of II: Predicting dynamic changes in quality attributes of tablets due to disturbances in raw material properties using an independent residence time distribution model
| Contributor(s):: Peterwitz, M, Buchgeister, SMeier, R, Schembecker, G
Continuous manufacturing of pharmaceuticals promises many advantages regarding economics and quality. However, tracing deviating material in such processes is much more challenging than in batch processes due to axial back-mixing. The literature has proven the traceability of disturbances in the...
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Twin screw granulation - review of current progress
| Contributor(s):: Thompson, M. R.
Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of Research Article has...
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Twin-screw melt granulation: Current progress and challenges
| Contributor(s):: Kittikunakorn, Nada, Liu, Tongzhou, Zhang, Feng
Twin-screw melt granulation (TSMG) is a new alternative method for granulation that offers several advantages over wet and dry granulation methods. TSMG has rapidly gained interest over recent years in the pharmaceutical industry. Since it is an inherently continuous process with controlled...
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Towards a Continuous Manufacturing Process of Protein-Loaded Polymeric Nanoparticle Powders
| Contributor(s):: Schiller, Stefan, Hanefeld, Andrea, Schneider, Marc, Lehr, Claus-Michael
To develop a scalable and efficient process suitable for the continuous manufacturing of poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing ovalbumin as the model protein. PLGA nanoparticles were prepared using a double emulsification spray-drying method. Emulsions were prepared using...
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Towards a novel continuous HME-Tableting line: Process development and control concept
| Contributor(s):: Sacher, Stephan, Celikovic, Selma, Rehrl, Jakob, Poms, Johannes, Kirchengast, Martin, Kruisz, Julia, Sipek, Martin, Salar-Behzadi, Sharareh, Berger, Hannes, Stark, Gerald, Horn, Martin, Khinast, Johannes G.
The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous...
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Towards Continuous Primary Manufacturing Processes-Particle Design through Combined Crystallization and Particle Isolation
| Contributor(s):: Steenweg, C, Kufner, ACHabicht, J, Wohlgemuth, K
Integrated continuous manufacturing processes of active pharmaceutical ingredients (API) provide key benefits concerning product quality control, scale-up capability, and a reduced time-to-market. Thereby, the crystallization step, which is used in approximately 90% of API productions, mainly...
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The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation
| Contributor(s):: Ryckaert, Alexander, Ghijs, Michael, Portier, Christoph, Djuric, Dejan, Funke, Adrian, Vervaet, Chris, De Beer, Thomas
The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying...
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The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing
| Contributor(s):: Dadou, SM, Tian, YWLi, S, Jones, DS, Andrews, GP
Complications associated with uncontrolled hypertension are considered the major cause of premature death worldwide. Fixed-dose combinations (FDCs) offer an alternative approach to polypharmacy with the aim to improve patient compliance. Process Analytical Technology (PAT) is gaining momentum as...