Flow chemistry, AI, and NMR: A next-gen approach to scalable API production
by Bruker BioSpin Group · News-MedicalIn this interview, News Medical speaks with Guillaume Bentzinger, Project Manager at Novalix; Luis Carrillo, Managing Director at De Dietrich France; Philippe Robin CEO of Alysophil; and Alejandro Bara-Estaún, Solution Product Manager at Bruker about how flow chemistry, artificial intelligence (AI), and nuclear magnetic resonance (NMR) are being integrated to transform the production of active pharmaceutical ingredients (APIs).
Can you please introduce yourself and your role in the PiPAC project?
What was the driving motivation behind the PIPAc initiative?
What specific challenges did you encounter during the synthesis of propofol and fentanyl?
For fentanyl, we explored both conventional and novel synthesis routes. We obtained interesting results for both strategies but for time and industrial plan size reasons, we decided to focus only on the last step for the final industrial demonstrator. One constraint was working under regulatory constraints, which required us to build a restricted-area facility and initially explore non-regulated intermediates. Another was to find conditions avoiding precipitations in order to run the synthesis under flow conditions.
Image Credit: Novalix
How did De Dietrich approach scaling up the lab flow chemistry processes into a functional industrial demonstrator unit?
- Feasibility study
- Process definition
- Basic and detailed engineering
- Final construction
The challenge was combining a regulated pharma environment, ATEX compliance, and new continuous flow chemistry processes, all within a 15-square-meter lab footprint.
Can you tell us more about the 3D-printed flow reactor and its development?
How did De Dietrich ensure the successful integration of AI and process automation?
We implemented a market-standard OPC UA communication protocol. Siemens PCS 7 managed the control architecture, with WinCC for supervision. Our instrumentation streams real-time data, coming from advanced NMR analytics and AI use to adapt process parameters, fully automated workflows in line with Pharma 4.0 principles.
Could you explain how Alysophil applied AI to optimize API production in this project?
What makes this AI system different from traditional process control methods?
What do you envision for the future of flow chemistry and AI integration in pharmaceutical manufacturing?
Image Credit: Bruker BioSpin Group
How do you see the role of in-line NMR evolving further in combination with continuous-flow chemistry and AI for API production?
Alejandro Bara-Estaún: In-line NMR plays a crucial role in making flow chemistry processes more robust, traceable, and controllable. With instruments like the Fourier 80 integrated into orchestration PAT softwares like synTQ, we can measure the concentration of products like fentanyl and also track conversion, yield, and concentration in real-time.
As this technology matures, I believe we'll see in-line NMR becoming the cornerstone of Pharma 4.0 facilities.
What were the key integration challenges you faced when connecting the benchtop NMR system with the flow reactor and AI architecture, and how were they overcome?
About the speakers
Guillaume Bentzinger is a Project Manager at Novalix, where he leads synthetic chemistry development in Process Chemistry. He holds a PhD in medicinal chemistry from the University of Amiens (Université de Picardie Jules Verne) and conducted postdoctoral research at Almac Discovery and Queen’s University Belfast. His expertise spans both academic and industrial research, with a focus on continuous flow chemistry and scalable synthesis, mainly for pharmaceuticals.
Luis Carrillo is the Managing Director of De Dietrich Process Systems France. He holds a chemistry degree from the University of Barcelona and an executive MBA from IESE Business School. With over a decade of experience in chemical engineering and process systems, he specializes in designing and implementing industrial-scale solutions for regulated sectors like pharmaceuticals and fine chemicals.
Alejandro Bara-Estaún is the Solution Product Manager for (bio)Process and Process Analytical Technology within Bruker BioSpin. He obtained his Ph.D. in Inorganic Chemistry at the University of Bath (UK) in collaboration with Bristol University and Evonik (Germany). He then undertook a two-year postdoctoral position at Bruker, leading the PIPAc project in collaboration with Alysohpil, Novalix, and De Dietrich.
About Bruker BioSpin Group
Bruker BioSpin’s customers in academic, government, industrial, and pharmaceutical sectors rely on these technologies to gain detailed insights into molecular structure, dynamics, and interactions. Our solutions play a key role in structural biology, drug discovery, disease research, metabolomics, and advanced materials analysis. Recent investments in lab automation, optical imaging, and contract research services further strengthen our ability to support evolving customer needs and enable scientific innovation.
Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.