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Development and process scaling of repeat mini-blending as a complementary approach to deliver continuous direct compression
Peer-reviewed journal | 13 Nov 2024 | Contributor(s):: Martin Prostredny, Hikaru Graeme Jolliffe, Richard Elkes, Khalid Maqsood, Yunfei Li Song, Gavin Reynolds, Bernhard Meir, John Robertson
Process integration efforts in the pharmaceutical industry have led to an increased interest in Direct Compression, including Continuous Direct Compression. Accurate scale-up of powder blending and prediction of blend Critical Quality Attributes (CQAs) is key. The present work takes a modified...
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Process intensification of pharmaceutical powder blending at commercial throughputs by utilizing semi-continuous mini-blending
Peer-reviewed journal | 13 Aug 2024 | Contributor(s):: Maarten Jaspers, Florian Tegel, Timo P. Roelofs, Fabian Starsich, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff
Process intensification involves the miniaturization of equipment while retaining process throughput and performance. The pharmaceutical industry can benefit from this approach especially during drug product development, where the availability of active pharmaceutical ingredients (API) is often...
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Process Intensification via End-to-End Continuous Manufacturing of Atorvastatin Calcium Using an Integrated, Modular Reaction-Crystallization-Spherical Agglomeration-Filtration-Drying Process
Peer-reviewed journal | 23 Jul 2024 | Contributor(s):: Parvaresh, Rojan, Nagy, Zoltan K.
Continuous manufacturing can show potential benefits over batch processing in lower turnaround times and smaller footprint in addition to higher productivity, adaptability, and consistent product quality. Although these possible benefits exist, there are also challenges in integrating the various...
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Continuous Flow-Facilitated CB2 Agonist Synthesis, Part 2: Cyclization, Chlorination, and Amination
Peer-reviewed journal | 24 Apr 2024 | Contributor(s):: Prieschl, Michael, Sagmeister, Peter, Moessner, Christian, Sedelmeier, Joerg, Williams, Jason D., Kappe, C. Oliver
A new route to the cannabinoid receptor type 2 agonist, RG7774, has been developed circumventing an alkylation with poor regioselectivity as the final step. In the new synthetic route, this side chain is incorporated from the beginning. In this article, the development of the final four...
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A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles
Peer-reviewed journal | 24 Apr 2024 | Contributor(s):: Hsieh, Hsiao-Wu, Griffin, Daniel J., Ananthoji, Padmini, Avci, Nadide Hazal, Brown, Derek B., Ericson, Ari, Fostinis, James D., Irfan, Muhammad, Langille, Neil, Lovette, Michael A., Murray, James I., Spada, Simone, Thiel, Oliver R., Aiello, Frankie, Daou, Joseph, Goudas-Salomon, Nicole, Pan, Ende, Sarkar, Nandini, Wimalasinghe, Rasangi, Wu, Zufan Steven, Zeng, Alicia, Beaver, Matthew G., Cohen, Carolyn M.
Herein, we report the development of an integrated continuous manufacturing (CM) process for the penultimate step in the synthesis of apremilast, the drug substance (DS) of the commercial product Otezla. This development effort was motivated by the desire to create an alternative manufacturing...
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Continuous Manufacturing: Many Want It, But Here's Why Few Have It
Website | 20 Feb 2024 | Contributor(s):: Ioanna Deni
Continuous manufacturing remains a key objective among bioprocessing professionals. While continuous bioprocessing isn’t a new concept, having been applied in the production of both old and new products, significant technological advancements set the stage for its wider adoption.
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Process Intensification and Integration Studies for the Generation of a Key Aminoimidazole Intermediate in the Synthesis of Lanabecestat
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Znidar, D, Cantillo, DInglesby, P, Boyd, A, Kappe, CO
An improved synthetic procedure for the multistep synthesis of aminoimidazole 6, a key intermediate in the preparation of lanabecestat (AZD3293/LY3314814), is described. Under intensified conditions (high temperature and elevated pressure), the overall processing time and required amounts of...
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Pharmaceutical industry perspectives on flow chemocatalysis and biocatalysis
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Martin, LL, Peschke, TVenturoni, F, Mostarda, S
In response to a growing demand for more sustainable and cost-effective synthetic processes, the pharmaceutical industry is increasingly relying on continuous manufacturing as a valuable alternative to conventional batch processing. Particularly, flow processing may enable process intensification...
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Mathematical modeling and digital design of an intensified filtration-washing-drying unit for pharmaceutical continuous manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Destro, Francesco, Hur, Inyoung Wang, Vivian Abdi, Mesfin, Feng, Xin, Wood, Erin, Coleman, Simon, Firth, Paul, Barton, Alastair, Barolo, Massimiliano, Nagy, Zoltan K.
This paper introduces a comprehensive mathematical model of a novel integrated filter-dryer carousel system, designed for continuously filtering, washing and drying a slurry stream into a crystals cake. The simulator includes models for dead-end filtration, cake washing and convective cake...
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Forbidden Chemistries - Paths to a Sustainable Future Engaging Continuous Processing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Gutmann, B, Kappe, CO
Optimizing current chemical processes alone does not yield the improvements required in the fine chemical and pharmaceutical industries. At least partially, a switch from batch to continuous manufacturing is needed. Cost-, time-, and atom-efficient routes frequently demand the application of high...
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Expedient preparation of active pharmaceutical ingredient ketamine under sustainable continuous flow conditions
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Kassin, VEH, Gerardy, RToupy, T, Collin, D, Salvadeo, E, Toussaint, F, Van, Hecke, K, Monbaliu, JCM
A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The procedure relies on the main assets of continuous flow processing, starts from commercially available chemicals, utilizes low toxicity...
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Continuous manufacturing of drug substance and small molecules: process and equipment view
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Yazdanpanah, Nima
The continuous manufacturing of pharmaceutical compounds and fine chemicals is in high interest for the industry due to significant technical, quality, and economical advantages. This manufacturing method has its own challenges. Beside the more efficient, safer, and greener synthesis rout, a new...
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Continuous manufacturing technologies in upstream pharmaceutical supply chains: Combining engineering and managerial criteria
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Aulakh, PK, Settanni, E, Srai, JS
The COVID-19 pandemic exposed vulnerabilities in upstream pharmaceutical supply chains (PSC). One is that the global supply of active pharmaceutical ingredients (APIs) is overly dependent on few locations and large-scale batch manufacturing. Regulators hope to enable more dependable location...
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Accelerating biologics manufacturing by modeling or: Is Approval under the QbD and PAT approaches demanded by authorities acceptable without a digital-twin?
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Zobel-Roos, Steffen, Schmidt, Axel Mestmäcker, Fabian Mouellef, Mourad, Huter, Maximilian, Uhlenbrock, Lukas, Kornecki, Martin, Lohmann, Lara, Ditz, Reinhard, Strube, Jochen
Innovative biologics, including cell therapeutics, virus-like particles, exosomes, recombinant proteins, and peptides, seem likely to substitute monoclonal antibodies as the main therapeutic entities in manufacturing over the next decades. This molecular variety causes a growing need for a...