The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

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...

Development of a Continuous Flow Grignard Reaction to Manufacture a Key Intermediate of Ipatasertib

25 Jun 2024 | Contributor(s): Kaldre, Dainis, Stocker, Severin, Linder, David, Reymond, Helena, Schuster, Andreas, Lamerz, Jens, Hildbrand, Stefan, Püntener, Kurt, Berry, Malcolm, Sedelmeier, Jörg

This article outlines the development of a continuous flow process for the manufacture of a key intermediate of the active pharmaceutical ingredient ipatasertib for the treatment of metastatic castration-resistant prostate cancer and triple-negative metastatic breast cancer. The reaction sequence...

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...

Innovation and Continuous Improvement in Pharmaceutical Manufacturing

28 Mar 2024 | Document | Contributor(s): Ajaz Hussain (Chairperson) Raafat Fahmy (CVM), William Bargo (CVM), Robert Coleman, Robert (ORA), Elise Murphy (ORA), Frank Holcombe Jr (CDER), Chris Watts (CDER), See Lam (CDER), Jon Clark (CDER), Christopher Joneckis (CBER), John Dietrick (CDER), Diana Kolaitis (ORA), Vilayat Sayeed (CDER), Mai Huynh (CVM), Norman Schmuff (CDER), Andrew Chang (CBER)

The PAT Team and Manufacturing Science Working Group Report: A Summary of Learning, Contributions and Proposed Next Steps for Moving towards the "Desired State" of Pharmaceutical Manufacturing in the 21st Century

A Perspective on Quality by Design: A Preclinical Opportunity

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

A Shared Vision for Pharmaceutical Development and Manufacturing in the 21st Century: Contributions of the PAT Initiative

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

The Subcommittee on Process Analytical Technologies (PAT): Closing Remarks

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

The Process Analytical Technology Initiative: PAT and the Pharmacopeias

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

The PAT Initiative A part of the Pharmaceutical Quality for the 21st Century Initiative  PAT and the USP Opportunities for the USP to support the PAT Framework

Utilizing PAT to Monitor and Control Bulk Biotech Processes

27 Mar 2024 | Document | Contributor(s): Rick E. Cooley

1.What is and isn’t PAT? 2.Implementing PAT in Manufacturing: What does it take? 3.Characteristics of bulk, biotech API processes 4.Why PAT? 5.Review of PAT technologies utilized 6.PAT application examples

Continuous Manufacturing for Pharmaceutical Solid Dosage Forms (On-Demand)

31 Jan 2024 | Seminars | Contributor(s): Atul Dubey, Fernando Muzzio, Gerardo Callegari, Lucy L. Botros, Ravendra Singh, James Scicolone, Andres Roman, Sonia Modarres Razavi

Course Description: This self-paced curriculum contains fourteen self-paced modules and three recordings of live virtual education on Pharmaceutical Continuous Manufacturing (PCM). Learners will have access to the following: A recording of the introductory session covering topics such as...

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

09 Jun 2023 | Peer-reviewed journal | 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 | 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 a novel continuous HME-Tableting line: Process development and control concept

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

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 Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing

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