An audit of pharmaceutical continuous manufacturing regulatory submissions and outcomes in the US

20 Nov 2024 | Peer-reviewed journal | Contributor(s): Adam C. Fisher, William Liu, Andreas Schick, Mahesh Ramanadham, Sharmista Chatterjee, Raphael Brykman, Sau L. Lee, Steven Kozlowski, Ashley B. Boam, Stelios C. Tsinontides, Michael Kopcha

Continuous manufacturing (CM) sends materials directly and continuously to the next step of a process, eliminating hold times and reducing processing times. The potential benefits of CM include improved product quality, reduced waste, lower costs, and increased manufacturing flexibility and...

The role of digital twins in driving sustainability

29 Oct 2024 | Peer-reviewed journal | Contributor(s): Deborah McElhone, Barrie Cassey, Kamal Abu-Hassan

As the pharmaceutical sector endeavours to become more sustainable, we hear how digital twins – virtual replicas of systems or products that can help predict performance – are supporting the industry in its efforts.

Continuous manufacturing: Changing the paradigm in the pharmaceutical manufacturing sector

23 Sep 2024 | Magazine | Contributor(s): Indu Bhushan

The author explains how continuous manufacturing is reshaping pharmaceutical production

The Rise of Continuous Manufacturing in Pharma

13 Aug 2024 | Website | Contributor(s): Editorial Team

"Mr Indu Bhushan, CEO and Director of STEERLife shares his insights on the transformative journey of continuous manufacturing, and the advanced technologies that have propelled this paradigm shift. He also throws light on how continuous manufacturing has accelerated drug development...

Continuous Manufacturing in the Pharmaceutical Industry: Enhancing Drug Production

23 Jul 2024 | Website | Contributor(s): Timmerman, Siebe

A significant shift towards continuous manufacturing (CM) is currently underway in the pharmaceutical industry. Unlike the more commonly used batch processing, CM operates continuously. This method potentially offers increased efficiency, agility, and flexibility in the manufacturing of drug...

Embracing continuous manufacturing in the pharmaceutical industry

03 Jun 2024 | Website | 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."

Continuous Flow Intensification for the Synthesis of High-Purity Warfarin

10 May 2024 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 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

Quality & Regulatory Solutions for PAT in Continuous Manufacturing

04 Jan 2024 | Magazine | Contributor(s): Gabriella Dahlgren, Kevin A. Macias, Antonio R. Moreira, Duncan R. Thompson, Christoph Herwig, Robert Dream

Process analytical technology (PAT) is perceived as the main enabler for a robust control strategy with continuous manufacturing (CM) because process analytical technology can aid in implementing continuous manufacturing throughout the entire life cycle. This article discusses quality and...

Continuous Manufacturing to Improve Pharmaceutical Quality: Research Examples and Opportunities

20 Nov 2023 | Workshop | Contributor(s): Geng Tian

Continuous manufacturing (CM) of drug substances and drug productsProcess modeling and simulation (M&S) for CM at FDACM research highlightsOpportunities of CM for generic drug productsPharmaceutical Quality Symposium 2023: Quality, Supply Chain & Advanced Manufacturing -...

Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

09 Jun 2023 | Peer-reviewed journal | 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.

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

09 Jun 2023 | Peer-reviewed journal | 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 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 Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Adam C Fisher, Mark-Henry Kamga, Cyrus Agarabi, Kurt Brorson, Sau L Lee, Seongkyu Yoon

There is a trend across the pharmaceutical sector toward process intensification and continuous manufacturing to produce small-molecule drugs or biotechnology products. For biotechnology products, advancing the manufacturing technology behind upstream and downstream processes has the potential to...

The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality - M4Q(R1)

09 Jun 2023 | Document

Guideline aims to harminze the approach to the eCTD to create efficiencies for reviewers and decrease the rejection rate for drug applications.

Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

09 Jun 2023 | Document

Document highlights the product lifecycle and the various considerations for maintaining consistent quality through both shelf life and entire lifecycle.

Small-Volume Continuous Manufacturing of Merestinib. Part 1. Process Development and Demonstration

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cole, KP, Reizman, BJHess, M, Groh, JM, Laurila, ME, Cope, RF, Campbell, BM, Forst, MB, Burt, JL, Maloney, TD, Johnson, MD, Mitchell, D, Polster, CS, Mitra, AW, Boukerche, M, Conder, EW, Braden, TM, Miller, RD, Heller, MR, Phillips, JL, Howell, JR

Development of a small volume continuous process that used a combination of batch and flow unit operations to manufacture the small molecule oncolytic candidate merestinib is described. Continuous processing was enabled following the identification and development of suitable chemical...

Small-Volume Continuous Manufacturing of Merestinib. Part 2.Technology Transfer and cGMP Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Reizman, Brandon J., Hess, Molly, Burt, Justin L., Maloney, Todd D., Johnson, Martin D., Laurila, Michael E., Cope, Richard F., Luciani, Carla V., Buser, Jonas Y., Campbell, Bradley M., Forst, Mindy B., Mitchell, David, Braden, Timothy M., Lippelt, Christopher K., Boukerche, Moussa, Starkey, Derek R., Miller, Richard D., Chen, Jing, Sun, Baoquan, Kwok, Martin, Zhang, Xin, Tadayon, Sam, Huang, Ping

Technology transfer of a small volume continuous (SVC) process and Current Good Manufacturing Practices (cGMP) manufacturing of merestinib are described. A hybrid batch-SVC campaign was completed at a contract manufacturing organization under cGMP. The decision process by which unit operations...