On September 26-28 the 14th CFRT for Industrial Applications Symposium took place at the Portmarnock Hotel & Golf Links in Dublin, Ireland.
On the first day a Pre-Conference Workshop on Continuous Manufacturing Process Development and Scale-up: From Lab to Manufacturing was organised, with Nima Yazdanpanah, Principal at Procegence, as instructor. Different stages of process development, scale-up, and manufacturing were discussed. Practices on the flow chemistry, equipment design, scale-up, equipment characterization, system dynamic and control strategies, and CMC regulatory material preparation were proposed. Moreover, some cases studies were demonstrated for synthesis, crystallization, process dynamic, digital twin, RTD, and QbD. The course can be summarised as an in-depth analysis of the critical aspects to deliver a process that is efficient, reliable, and easy to control thanks to Process design and system integration.
The afternoon continued with food and drinks during a relaxing fireside chat and Q&A at the Seaview Lounge with a renowned Irish International, and British & Irish Lions, Rugby Star as Guest Speaker sponsored by SK Pharmteco. Gordon D’Arcy is building a reputation for his unique insight and tales of his experiences in rugby, particularly around the incorporation of sports psychology & mental preparation into the modern game. Very inspiring his thoughts around friendship and respect among mates and rivals.
The second day started with the welcome of Tks Publisher members and of the two chairpersons Olivier Dapremont, Executive Director, Process Technologies at AMPAC Fine Chemicals LLC, an SK pharmteco company and Marcus Baumann, Professor in Continuous Flow Chemistry at the University College Dublin.
Federico Galvanin, Associate Professor of Chemical Engineering at University College London, opened the morning session with a Keynote presentation on the cutting-edge development of autonomous platforms for swift kinetic model identification in flow reaction systems. Emphasizing the crucial role of model-based design of experiments (MBDoE) techniques, the presentation showcased their application in unmanned experimental campaigns. The integration of MBDoE with machine learning was explored for kinetic model selection, agile identification of reliability maps, and the rapid establishment of surrogate models.
Sebastian Härtner, Process Development – Principal Project Lead from Merck Electronics, discussed an innovative approach to API production using intensified processes and modular automation. This “factory in a box” concept enables the seamless transfer of lab or pilot equipment, increasing efficiency, reducing the CO2 footprint, and accelerating time-to-market by up to 50%.
Helen Pointon, Process development scientist – Continuous Processing, for Astrazeneca and Wouter Bolt, Sales manager at Zeton gave a combined speech on the utilization of continuous technologies and kinetic modeling to optimize the synthesis of an amide intermediate in balcinrenone production. They demonstrated that the shift from batch to continuous processes reduced costs, solvent use, and enhanced efficiency, showcasing a transferable example for AstraZeneca’s Continuous API facility.
Kevin van Eeten, Director Development & Flow Solutions at Flowid, delved into the batch versus continuous manufacturing debate, sharing insights from diverse industries. He highlighted economic opportunities in combining flow chemistry and reactor engineering, showcasing successful applications for business continuity, growth, and sustainability.
Robert Moylan, Scientific advisor at Eli Lilly, discussed GMP considerations for continuous manufacturing in the pharmaceutical industry, emphasizing the benefits of high throughput with smaller-scale equipment. Key points included meeting cGMP requirements and implementing operational strategies tailored for continuous processes, addressing issues like batch definition and process monitoring.
Ryan Woods, Director, PR&D Engineering at AMPAC Fine Chemicals, highlighted the growing popularity of continuous chemistry development, acknowledging challenges in transitioning from traditional batch processes. While bench-scale optimization is established, scale-up to pilot and commercial scales faces hurdles. AFC’s approach, fitting processes to pre-qualified modules, enables rapid GMP clinical material production.
Daqing Che from Raybow highlighted the shift in chemical process innovation. Traditionally reliant on reaction innovations, modern progress emphasizes specific reactor and equipment advancements. Case studies, particularly in diazo and azide processes, indicated this transformative approach.
The afternoon opened with a Roundtable on Challenges and opportunities in using continuous flow in API synthesis at scale: industry and regulatory perspectives moderated by Anita Maguire Professor of Pharmaceutical Chemistry at University College Cork in collaboration with The Science Foundation Ireland Research Centre for Pharmaceuticals (SSPC).
The roundtable covered key topics, including the importance of biocatalysis and upskilling graduates in flow, raising awareness of photochemistry and electrochemistry. Discussions emphasized the need for more flow labs, carbon footprint case studies, understanding regulatory expectations, and expanding equipment and chemistry capabilities. Panelists also highlighted the potential of 3D printing, inclusion of supporting technologies like crystallization, and the development of standard practices for dangerous chemistries. The discussion extended to simplifying supply chains with on-site flow reactors and pushing the boundaries of chemistry for new reaction pathways in complex materials.
Experts involved in the discussion: Megan Smyth – Almac Sciences, Gary Morris – APC, Ryan Woods- AMPAC Fine Chemicals (an SK Pharmteco company), Robert Moylan – Eli Lilly, Paul Phillips- MSD, Nima Yazdanpanah – Procegence, Marcus Bauman- University College Dublin
The day continued with a combined speech of Andrea Adamo – Zaiput Flow Technologies, and John D Holcombe – W. L. Gore & Associates which addressed scalable technology for continuous heterogeneous catalysis, focusing on hydrogenation. Traditional batch reactors face safety issues, inefficiencies, and high costs. The talk introduced the Gore Structured Catalyst, discussing its tunable properties and a modular, scalable reactor design, showcasing improved catalyst utilization, temperature control, and scalability in a hydrogenation case study.
The last session of the day was devoted to the Academia Corner with highlights from the poster session:
Max Besenhard – University College London – How to Close the Loop: Autonomous Flow Chemistry for Process and Material development
Ella Cooper – University College Cork – The α-alkylation of ketones in continuous flow
Anita Maguire – University College Cork – Enhancing the Synthetic Utility of α-Diazocarbonyl Compounds through Continuous Flow Technology
Thomas Rehm – Fraunhofer Institute for Microengineering and Microsystems IMM – Polymeric foils as key element of the falling film microreactor: a concept study for enabling scalable heterogeneous catalysis in flow
Aravind Senthil Vel – CEISAM, Nantes University – Filtering-assisted Bayesian Optimization: Leveraging Autonomous Flow Reactors and Machine Learning for Reaction Optimization involving mixed variables
The day ended with a networking event at the Jameson Distillery where guests learnt about the history of Jameson, the process of whiskey making and took part in a whiskey tasting. While enjoying dinner and participating in dances, participants had the opportunity to network and do business.
Professor Oliver Kappe, University of Graz, opened the last day of the conference with a Keynote speech emphasizing the challenges and opportunities in chemical manufacturing, particularly in the face of global issues like population growth and climate change. He advocated for continuous-flow reactors with micro- or millimeter-sized channels, highlighting their advantages in safety, heat transfer, and handling hazardous reactions. The talk presented recent examples from his lab, showcasing applications relevant to pharmaceutical preparation.
Eoin Bourke, Process Development Scientist at APC, focused on continuous synthesis of an API intermediate through flow chemistry, aiming to enhance scale-up yields. He explained that by optimizing reactions with a tailored flow reactor and employing Computational Fluid Mechanics, a fully scalable, continuous process with impressive yields is achieved, demonstrating flow chemistry’s potential in overcoming scale-up challenges.
Fabien Sguerra, R&D project leader at Seqens, presented the continuous manufacturing of an API with high T/P conditions (>200°C, >15 Bar), optimized for ton-scale production using flow conditions. It emphasized low environmental impact through water synthesis and detailed the lab-scale R&D and challenges faced during pilot plant scale-up.
Michael Nonnenmacher, Evonik Operations, discussed the multi-step flow synthesis of an intermediate for an analgesic drug, emphasizing the flexibility of flow reactor systems. He covered challenges and solutions for scale-up, selection criteria for reaction setups, and economic and sustainability benefits, showcasing Evonik’s expertise in continuous processing.
Nima Yazdanpanah from Procegence addressed regulatory considerations in continuous drug substance manufacturing. The presentation navigated through FDA and ICH quality guidance, offering insights into workflow, challenges, and specific requirements across various stages of process development and control, emphasizing aspects like QbD, RTRT, and GMP.
Manuel Nuno, Chief Scientific Officer at Vapourtec, explored advances in continuous flow, covering various reactor types such as tubular, chip, and column reactors. The benefits and drawbacks of each were discussed, emphasizing the challenges of handling gases and solids. The presentation also addressed using continuous stirred tank reactors (CSTR) and explored optimizing reactions with machine learning. The final part focused on fast flow peptide synthesis (FF-SPPS) and its efficient scaling in lab and pilot settings, leveraging real-time data for improved control.
Alain George, Fluitec, highlighted the energy-saving potential of mass transfer-optimized flow reactors compared to conventional ones, particularly for fast gas-liquid reactions. He focused on Contiplant flow reactors, showcasing advantages, a case study on flow calorimetric measurements, and a scale-up concept with a mixer-heat exchanger, ensuring constant mass and heat transfer.
Etienne Baco and Virginie Maurel, La Mesta Chimie Fine, focused on the significance of continuous flow chemistry in industrial applications, emphasizing its benefits in safety, productivity, and environmental impact reduction. The speech detailed a 20-year journey in developing continuous flow equipment, showcasing examples where transitioning from batch to continuous flow processes significantly improved environmental footprints, reducing solvent and reagent consumption while enhancing yields.
Gabriela Grasa Mannino from the U.S. Pharmacopeia discussed the challenges hindering the wider adoption of continuous manufacturing despite technological advancements. She highlighted knowledge barriers and introduced the USP Continuous Manufacturing Knowledge Center, a digital platform fostering collaboration, sharing best practices, and addressing regulatory concerns to support industry-wide adoption.
David Font Gimbernat, Medichem, underlined how they adopted continuous flow technology in pharmaceutical production, optimizing an organometallic reaction under cryogenic conditions. Transitioning from a home-made flow system to Corning flow technology, they achieved doubled yields, increased enantiomeric excess, and enhanced safety in hazardous reactions, making flow chemistry indispensable for competitive advantage and safer scale-ups.
The last but not least speech of the day came from Nial Mitchell, Siemens Process Systems Engineering, who discussed challenges in tracking varying lot numbers during continuous drug substance manufacturing (CDSM). He proposed an approach using mechanistic modeling, residence time distribution (RTD) models, and flowsheet methodologies to monitor lot composition, addressing regulatory quality and optimizing production campaigns.
The symposium ended with a wrap-up of the event by the chairpersons and a comment from Tks Publisher staff who invited to stay tuned for the 15th CFRT.
It is worth underscoring the profound significance of the CFRT community in fostering an atmosphere of collaboration, innovation, and shared knowledge.
From my perspective, the bonds within the CFRT community are not only strengthening but evolving into a formidable force that propels the collective expertise of its members to new heights. The palpable trust among community members serves as a bedrock for the collaborative spirit that defines CFRT. This synergy has not gone unnoticed, as evidenced by the growing interest from a myriad of experts and companies eager to actively engage and contribute to the remarkable journey that CFRT has embarked upon.
As we reflect on the conclusion of this symposium, it becomes increasingly apparent that CFRT is not merely an event; it is a dynamic and flourishing community that continues to draw in diverse perspectives and expertise. The commitment and enthusiasm displayed by its members are laying the groundwork for a future marked by groundbreaking advancements, and the anticipation for the upcoming 15th CFRT is a testament to the community’s enduring impact and relevance.
You will have a better understanding of what I am saying during our 15th CFRT symposium which will take place in Weisbaden on 17-19 September 2024.
Have a look at our website at
www.cfrt-tks.com
Come and join the CFRT community!
