Process analytics for the new era of continuous RNA manufacturing

23 Jul 2024 | Contributor(s): Botonjic-Sehic, Edita

In this article, Edita Botonjic-Sehic, Head of Process Analytics and Data Science at ReciBioPharm, examines the need for a digitally controlled continuous manufacturing process to correct the shortcomings of the current standard of batch processing. She highlights the critical role in-line...

Continuous Flow Intensification for the Synthesis of High-Purity Warfarin

10 May 2024 | Contributor(s): Silva-Brenes, Diana V., Reyes-Vargas, Stephanie K., Duconge, Jorge, Vlaar, Cornelis, Stelzer, Torsten, Monbaliu, Jean-Christophe M.

While racemic warfarin was initially commercialized as a rodenticide, it has become the most prescribed anticoagulant drug for prevention of blood clots and is part of the World Health Organization’s list of essential medicines. The synthesis of warfarin appears straightforward, consisting of a...

Rapid production of the anaesthetic mepivacaine through continuous, portable technology

24 Apr 2024 | Contributor(s): Díaz-Kruik, Pablo, Paradisi, Francesca

Local anaesthetics such as mepivacaine are key molecules in the medical sector, so ensuring their supply chain is crucial for every health care system. Rapid production of mepivacaine from readily available commercial reagents and (non-dry) solvents under safe conditions using portable,...

Multi-step Flow Synthesis of the Anthelmintic Drug Praziquantel

24 Apr 2024 | Contributor(s): Phull, Manjinder Singh, Bohara, Chander Singh, Gundla, Rambabu, Mainkar, Prathama S., Jadav, Surender Singh

Praziquantel (PZQ; Brand name: Biltricide) is categorized as an anthelminthic drug, and it is used for the treatment of Schistosomiasis and other parasitic infections. The World Health Organization (WHO) has classified it as one of the essential and emergency medicines needed across the globe....

Continuous Flow-Facilitated CB2 Agonist Synthesis, Part 2: Cyclization, Chlorination, and Amination

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...

A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles

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...

Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis

09 Jun 2023 | Contributor(s): Madarasz, L, Kote, AGyurkes, M, Farkas, A, Hambalko, B, Pataki, H, Fulop, G, Marosi, G, Lengyel, L, Casian, T, Csorba, K, Nagy, ZK

The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles...

Using a material property library to find surrogate materials for pharmaceutical process development

09 Jun 2023 | Contributor(s): Escotet-Espinoza, MS, Moghtadernejad, SScicolone, J, Wang, YF, Pereira, G, Schafer, E, Vigh, T, Klingeleers, D, Ierapetritou, M, Muzzio, FJ

Material properties are known to have a significant impact on pharmaceutical manufacturing performance, particularly for solid product processes. Evaluating the performance of a specific material, for example an active pharmaceutical ingredient or excipient, is critical during development stages...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi

While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...

Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi

While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi

While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...

Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development

09 Jun 2023 | 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...

Twin-screw melt granulation: Current progress and challenges

09 Jun 2023 | 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...

Twin screw granulation - review of current progress

09 Jun 2023 | 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...

Towards a novel continuous HME-Tableting line: Process development and control concept

09 Jun 2023 | 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...

Thin-Film Evaporator Model for Continuous Active Pharmaceutical Ingredient Manufacturing

09 Jun 2023 | Contributor(s): Lee, BW, Yin, KHSplaine, K, Roesch, B

Thin-film evaporator (TFE) is a popular continuous distillation/evaporation technology for pharmaceutical and fine chemical industries and has several equipment and process configurations that make fundamental modeling approaches very challenging. Specifically, moving wipers and lack of fluid...

Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): Sagandira, CR, Nqeketo, SMhlana, K, Sonti, T, Gaqa, S, Watts, P

Continuous flow chemistry has opened a new paradigm in both the laboratory and pharmaceutical industry. This review details the recently reported literature on continuous multistep telescoped synthesis of active pharmaceutical ingredients (APIs), inline flow downstream processing, in-process...

Towards a Greener Pharmacy by More Eco Design

09 Jun 2023 | Contributor(s): Baron, M

This review proposes an overview of the main trends explored by the pharmaceutical industry in order to develop a greener and smarter pharmacy minimizing any negative impact to the environment, and using more sustainable processes and drugs. If many drugs have their origin in nature, many active...

The scope of PAT in real-time advanced control of tablet quality

09 Jun 2023 | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

Continuous pharmaceutical manufacturing together with process analytical technology (PAT) provides a suitable platform for automatic feed-forward/feed-back (FF/FB) control of the end product quality as desired by quality by design (QbD)-based efficient manufacturing. The precise control of the...

The reality of in-line tablet coating

09 Jun 2023 | Contributor(s): Cahyadi, Christine, Chan, Lai Wah, Heng, Paul Wan Sia

The possibility of continuous processing in pharmaceutical tablet manufacturing is hampered by the viscoelastic recovery of tablets post-compaction. Compacted tablets are typically aged before coating to allow complete viscoelastic recovery so as to avoid subsequent coating defects. There has...

The Evolving State of Continuous Processing in Pharmaceutical API Manufacturing: A Survey of Pharmaceutical Companies and Contract Manufacturing Organizations

09 Jun 2023 | 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...

The Future of Pharmaceutical Manufacturing Sciences

09 Jun 2023 | Contributor(s): Rantanen, Jukka, Khinast Johannes

The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is...

The Changing Face of Process Development & Chemical Manufacturing - A View from the Regulators on Continuous Manufacturing

09 Jun 2023 | Contributor(s): Wiles, Charolotte

Industry wide there is a drive for resource efficiency and flexibility, to adapt quickly in what is increasingly becoming a volatile, changing marketplace. As the ‘patent cliff’ looms for many high-volume API’s, there is also a shift away from blockbusters towards lower volume, higher potency...