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...

Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant

09 Jul 2024 | Peer-reviewed journal | 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...

Automated and continuous synthesis of drug substances

24 Apr 2024 | Peer-reviewed journal | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrl, Jakob, Sagmeister, Peter, Lebl, René, Kruisz, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D., Kirschneck, Dirk, Kappe, C. Oliver, Horn, Martin

A continuous synthesis line was developed integrating different common reaction steps namely nitration, substitution and hydrogenation. Mesalazine as model drug substance was produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PAT strategy was implemented to equip the...

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 | Peer-reviewed journal | 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 Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Engisch, William, Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing,...

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

09 Jun 2023 | Peer-reviewed journal | 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,...

Twin-screw melt granulation: Current progress and challenges

09 Jun 2023 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients

09 Jun 2023 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 reality of in-line tablet coating

09 Jun 2023 | Peer-reviewed journal | 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 Future of Pharmaceutical Manufacturing Sciences

09 Jun 2023 | Peer-reviewed journal | 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 Future of Pharmaceutical Manufacturing Sciences

09 Jun 2023 | Peer-reviewed journal | 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...

Template-induced nucleation for controlling crystal polymorphism: from molecular mechanisms to applications in pharmaceutical processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Parambil, JV, Poornachary, SKHeng, JYY, Tan, RBH

Over the last two decades, the use of template surfaces to induce heterogeneous crystal nucleation has been explored primarily to address two different goals: first, as an alternative to the conventional seeding technique used for polymorph control and, second, as a technique to promote the...

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

09 Jun 2023 | Website | 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...

The Concept of Chemical Generators: On-Site On-Demand Production of Hazardous Reagents in Continuous Flow

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Dallinger, D, Gutmann, B, Kappe, CO

CONSPECTUS: In recent years, a steadily growing number of chemists, from both academia and industry, have dedicated their Research Article to the development of continuous flow processes performed in milli- or microreactors. The common availability of continuous flow equipment at virtually all...

Solid forms of pharmaceuticals: Polymorphs, salts and cocrystals

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sarma, B, Chen, JHsi, HY, Myerson, AS

Control and selection of the properties of active pharmaceutical ingredients is a crucial part of the drug development process. One major part of this process is the selection of an appropriate solid form. This review will discuss three major types of crystalline solids, polymorphs, salts and...

Simulated moving bed chromatography for the separation of enantiomers

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Rajendran, A, Paredes, G, Mazzotti, M

Simulated moving bed (SMB) chromatography, a continuous multi-column chromatographic process, has become one of the preferred techniques for the separation of the enantiomers of a chiral compound. Several active pharmaceutical ingredients, including blockbuster drugs, are manufactured using the...

Separation and Purification in the Continuous Synthesis of Fine Chemicals and Pharmaceuticals

09 Jun 2023 | Peer-reviewed journal | Contributor(s): O'Mahony, M, Ferguson, SStelzer, T, Myerson, A

The use to both chemists and chemical engineers working in flow synthesis, this chapter provides a summary of separation and purification operations that can be applied to flow synthesis reaction streams. Both single and biphasic separations for the liquid phase are detailed. Separation and...

Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and sustainable Fine-Chemical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Morin, Mathieu, Zhang, Wenyao, Mallik, Debasis, Organ, Michael G

Process analytical technology (PAT) is a system designed to help chemists better understand and control manufacturing processes. PAT systems operate through the combination of analytical devices, reactor control elements, and mathematical models to ensure the quality of the final product through...

Scaling continuous API synthesis from milligram to kilogram: extending the enabling benefits of micro to the plant

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Berton, M, de, Souza, JMAbdiaj, I, McQuade, DT, Snead, DR

The signature benefits of continuous flow are largely a result of a reactor's micro-sized features. However, as the technology gains industrial traction in the synthesis of active pharmaceutical ingredients (API), the reactors must be scaled to larger size to meet production demands. Often, the...

Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yu, Mingzhe, Omar, Chalak, Weidemann, Marcus, Schmidt, Alexander, Litster, James D., Salman, Agba D.

Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to...

Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

09 Jun 2023 | Peer-reviewed journal | 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...

Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Chopda, Viki, Gyorgypal, Aron Yang, Ou Singh, Ravendra Ramachandran, Rohit Zhang, Haoran Tsilomelekis, George Chundawat, Shishir PS, Ierapetritou, Marianthi G

Continuous bioprocessing is significantly changing the biological drugs (or biologics) manufacturing landscape by potentially improving product quality, process stability, and overall profitability, as was similarly seen during the adoption of advanced manufacturing processes for small molecule...