"Pharmaceutical Chemistry goes Flow: End-to-End Integration, Soft-Matter Process Concepts, and PAT-Quality Control"
by Prof. Dr. Volker Hessel,
Micro Flow Chemistry and Process Technology,
Department of Chemical Engineering and Chemistry,
Eindhoven University of Technology
Abstract
Multiple flows Flow Chemistry provides chemical intensification. Novel Process Windows (NPW) achieve the latter through exploration of unusual and typically harsh process conditions with much enhanced activation and also chance for different selectivity pattern [Hessel, ChemSusChem 2013]. Several flow chemistries were developed via high-T, high-p, high-c (solvent-free; alternative solvent) concepts, leading to a boost of reactivity. This is complemented by the implementation of new smart electromagnetic activation modes (photo, ultrasound, plasma, microwave, etc. with their discrete rotational, vibrational, electron levels) as powerful alternative to temperature activation. Once the single processing steps are intensified, they can be brought to a higher level of process integration and simplification.
From such highly elaborated process machinery, the next step change is to have smart synthesis equipment which operates biomimetic and largely autonomous: the ‘Robo-Chemist’ which enables the ‘March of the Machines’ [Ley, Angew. Chem. Int. Ed. 2015; Pedlow, Nature 2014].
ONE-FLOW The FET-Open project ONE-FLOW translates the ‘vertical hierarchy’ of chemical multistep synthesis with its complex machinery into self-organising ‘horizontal hierarchy’ of a compartmentalized flow reactor system – a biomimetic digital flow cascade machinery with just one reactor passage. To keep horizontal hierarchy manageable, orthogonality needs to be increased among the different consecutive reactions, and compartmentation is the right concept. The "Functional Solvent-Factory" is an integrated soft-matter reactor-separator system which uses switcheable designer solvents for reversible compartmentation. The winning point of nature is to have invented catalytic cascades. ONE-FLOW will uplift that by enabling the best bio- and chemocatalysts working door by door. 4 synthetic flow reaction networks ('metabolic pathways’) and 1 flow cascade driven by automated intelligence ('signaling pathway') will be developed, producing 4 Top-list 2020 drugs.
On-line PAT quality control A very fast flow chemistry reaction has been combined with a modified ultra-high-performance liquid chromatography (UHPLC) system allowing for very fast, lowest-volume sampling and analysis. A critical review of the chances in speeding up analytics and the challenges is given, including the reproducibility and robustness of the sampling. Furthermore, the ability and speed of the chosen set-up in order to capture process changes and adjust the process parameters properly is investigated. With the applied online sampling system, it was possible to perform, almost unattended and spending 12 times less sampling volume, a full factorial analysis of all relevant reaction conditions (243 experiments) in three days. Assuming a systematic difference compared to manual sampling and dilution of 0.5 % ± 1.4, online sampling avoids random errors due to automation.
Bio
Prof. Dr. Volker Hessel studied chemistry at Mainz University (PhD in organic chemistry, 1993). In 1994 he entered the Institut für Mikrotechnik Mainz GmbH (1996: group leader microreaction technology). In 2002, Prof. Hessel was appointed Vice Director R&D at IMM and in 2007 as Director R&D. In 2005 and 2011, Prof. Hessel was appointed as part-time and full professor at Eindhoven University of Technology, respectively, for the chair of “Micro Flow Chemistry and Process Technology”. He is honorary professor at TU Darmstadt, Germany, and guest professor at Kunming University of Science and Technology, China. Prof. Dr. Hessel is (co-)author of more than 420 peer-reviewed publications and 9 books (h index 51, Scopus). He received the AIChE Award “Excellence in Process Development Research” in 2007, the ERC Advanced Grant “Novel Process Windows” in 2010, the ERC Proof of Concept Grant in 2017 and the IUPAC ThalesNano Prize in Flow Chemistry in 2016. In the same year, the FET OPEN project ONE-FLOW was granted for which Prof. Hessel is as coordinator. In 2017, he received the ERC Proof of Concept Grant. He is Editor-in-Chief of the journal “Green Processing and Synthesis”. He was authority in the 35-man teamed Enquete Commission "Future of the Chemical Industry" of the parliament of Germany's state Nordrhein-Westfalia and is advisor of GSK for their Green Chemical Manufacturing Programme in Singapore.
Coffee, tea and cake will be served.