TY - CONF A1 - Maiwald, Michael A1 - Meyer, Klas T1 - Compact NMR spectroscopy: A versatile tool for automated continuous-flow production of chemicals and pharmaceuticals N2 - Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. T2 - Process Development Seminar Bayer AG Dormagen CY - Dormagen, Germany DA - 14.01.2019 KW - Process analytical technology KW - Low-field NMR spectroscopy KW - Online NMR spectroscopy KW - CONSENS PY - 2019 AN - OPUS4-47197 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Guhl, Svetlana A1 - Maiwald, Michael A1 - Kern, Simon A1 - Meyer, Klas A1 - Wander, Lukas A1 - Bornemann-Pfeiffer, Martin T1 - Produzieren Sie schon oder kalibrieren Sie noch? – Online-NMR-Spektrometer als Smarte Feldgeräte N2 - Der Übergang von der aktuellen Automatisierungslandschaft zur nächsten Generation von Automatisierungskonzepten für die Prozessindustrie hat bereits begonnen. Intelligente Funktionen der Sensoren vereinfachen ihre Anwendung und ermöglichen eine Plug-and-Play-Integration, auch wenn sie auf den ersten Blick komplexer erscheinen mögen. Dies ist die Basis für die Digitalisierung der Prozessindustrie und hilft uns, komplexere Prozesse schneller umzusetzen. Der Vortrag fasst die derzeit diskutierten allgemeinen Anforderungen an „Smarte Feldgeräte“ zusammen und diskutiert dieses am Beispiel eines smarten Online-NMR-Sensors. NMR-Spektroskopie bietet sich durch den Vorteil der direkten Vergleichsmethode (ohne Kalibrierung) für die Prozess-Steuerung an und verringert somit die Rüstzeiten. Zudem basiert der Sensor auf physikalisch motivierten Modellen (Indirect Hard Modeling, IHM), die sich modular kombinieren lassen. Die Methoden wurden anhand eines vorgegebenen pharmazeutischen Reaktionsschrittes im Rahmen des „Horizon 2020“-Projekts CONSENS der Europäischen Union demonstriert und validiert. Zuletzt werden Anforderungen an die Weiterentwicklung der Datenauswertemethoden diskutiert, um letztlich die semantische Information aus den Messdaten herauszulesen oder das in der Industrie 4.0 geforderte „durchgehende Engineering“ für die Automatisierungskomponenten zu ermöglichen. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessindustrie KW - Prozessanalytik KW - Online-NMR-Spektroskopie KW - Datenkonzepte KW - Datenanalyse KW - CONSENS PY - 2018 N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. AN - OPUS4-45934 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Gräßer, Patrick A1 - Wander, Lukas A1 - Guhl, Svetlana A1 - Bornemann-Pfeiffer, Martin A1 - Paul, Andrea A1 - Meyer, Klas A1 - Kern, Simon T1 - Already producing or still calibrating? – Online NMR spectroscopy as smart field device N2 - The departure from the current automation landscape to next generation automation concepts for the process industry has already begun. Smart functions of sensors simplify their use and enable plug-and-play integration, even though they may appear to be more complex at first sight. Monitoring specific information (i.e., “chemical” such as physico-chemical properties, chemical reactions, etc.) is the key to “chemical” process control. The talk introduces a smart online NMR sensor module provided in an explosion proof housing as example. This sensor was developed for an intensified industrial process (pharmaceutical lithiation reaction step) funded by the EU’s Horizon 2020 research and innovation programme (www.consens-spire.eu). Due to NMR spectroscopy as an “absolute analytical comparison method”, independent of the matrix, it runs with extremely short set-up times in combination with “modular” spectral models. Such models can simply be built upon pure component NMR spectra within a few hours (i.e., assignment of the NMR signals to the components) instead of tedious calibrations runs. Industry 4.0, IIoT, or Lab 4.0 will enable us to handle more complex processes in shorter time. Intensified production concepts require for adaptive analytical instruments and control technology to realize short set-up times, modular control strategies. They are based on a digitized Laboratory 4.0. T2 - GA-Conference CY - BASF, Ludwigshafen, Germany DA - 16.05.2018 KW - Process Monitoring KW - Online NMR Spectroscopy KW - Industrie 4.0 KW - Indirect Hard Modeling KW - Laboratory 4.0 KW - CONSENS PY - 2018 N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. AN - OPUS4-44895 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Guhl, Svetlana A1 - Kern, Simon A1 - Meyer, Klas A1 - Wander, Lukas A1 - Bornemann-Pfeiffer, Martin A1 - Maiwald, Michael T1 - Produzieren Sie schon oder kalibrieren Sie noch? – Online-NMR-Spektrometer als Smarte Feldgeräte T2 - Chemie Ingenieur Technik N2 - Der Vortrag zeigt allgemeine Anforderungen an "smarte Feldgeräte" und deren Entwicklung in den vergangenen Jahren. Am Beispiel eines smarten Online-NMR-Sensors, der in einem EU-Projekt von der BAM entwickelt wurde, wird die Umsetzung der Anforderung aufgezeigt. Schließlich werden weitere Technologieanforderungen und Lösungsansätze vorgestellt. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessanalytik KW - Prozessindustrie KW - Online-NMR-Spektroskopie KW - Datenkonzepte KW - Datenanalyse KW - CONSENS PY - 2018 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/cite.201855229 DO - https://doi.org/10.1002/cite.201855229 SN - 0009-286X N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. VL - 90 IS - 9 SP - 1236 EP - 1236 PB - Wiley-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-45901 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Gräßer, Patrick A1 - Wander, Lukas A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Kern, Simon T1 - Sustainable and Flexible Production of High Quality Chemicals and Pharmaceuticals Using Smart Sensors and Modular Production Units N2 - The departure from the current automation landscape to next generation automation concepts for the process industry has already begun. Smart functions of sensors simplify their use and enable plug-and-play integration, even though they may appear to be more complex at first sight. Monitoring specific information (i.e., “chemical” such as physico-chemical properties, chemical reactions, etc.) is the key to “chemical” process control. The talk introduces a smart online NMR sensor module provided in an explosion proof housing as example. This sensor was developed for an intensified industrial process (pharmaceutical lithiation reaction step) funded by the EU’s Horizon 2020 research and innovation programme (www.consens-spire.eu). Due to NMR spectroscopy as an “absolute analytical comparison method”, independent of the matrix, it runs with extremely short set-up times in combination with “modular” spectral models. Such models can simply be built upon pure component NMR spectra within a few hours (i.e., assignment of the NMR signals to the components) instead of tedious calibrations runs. The talk also generally covers current aspects of high-field and low-field online NMR spectroscopy for reaction monitoring and process control and gives also an overview on direct dissolution studies of API cocrystals. T2 - Chemistry Group Seminar Pfizer Inc. CY - La Jolla, California, USA DA - 09.03.2018 KW - Process Monitoring KW - Online NMR Spectroscopy KW - Smart Sensors KW - Indirect Hard Modeling KW - Modular Production KW - CONSENS PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-444382 AN - OPUS4-44438 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kern, Simon A1 - Wander, Lukas A1 - Meyer, Klas A1 - Guhl, Svetlana A1 - Gottu Mukkula, A. R. A1 - Holtkamp, M. A1 - Salge, M. A1 - Fleischer, C. A1 - Weber, N. A1 - Engell, S. A1 - Paul, Andrea A1 - Pereira Remelhe, M. A1 - Maiwald, Michael T1 - Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals JF - Analytical and Bioanalytical Chemistry N2 - Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce reconfiguration for fast product changes. To facilitate this flexibility by real-time quality control, we developed a solution that can be adapted quickly to new processes and is based on a compact nuclear magnetic resonance (NMR) spectrometer. The NMR sensor is a benchtop device enhanced to the requirements of automated chemical production including robust evaluation of sensor data. Beyond monitoring the product quality, online NMR data was used in a new iterative optimization approach to maximize the plant profit and served as a reliable reference for the calibration of a near-infrared (NIR) spectrometer. The overall approach was demonstrated on a commercial-scale pilot plant using a metal-organic reaction with pharmaceutical relevance. KW - NMR Spectroscopy KW - NIR Spectroscopy KW - Real-time process monitoring KW - Real-time quality control KW - Continuous processes KW - CONSENS KW - Data Fusion PY - 2019 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-480623 DO - https://doi.org/10.1007/s00216-019-01752-y SN - 1618-2642 SN - 1618-2650 VL - 411 IS - 14 SP - 3037 EP - 3046 PB - Springer Nature CY - Heidelberg AN - OPUS4-48062 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - THES A1 - Kern, Simon T1 - Prozessüberwachung mittels Niederfeld-NMR-Spektroskopie als Online-Methode N2 - Die Geräteentwicklungen im Bereich der Niederfeld-NMR-Spektroskopie im vergangenen Jahrzehnt ermöglichen den Einsatz kompakter, portabler Magnete mit geringen Streufeldern in Laborumgebungen und industriellen Produktionsanlagen. Somit werden neue Möglichkeiten für hochauflösende NMR-Experimente zur Reaktionsüberwachung eröffnet. Im Rahmen des EU-Projekts CONSENS wurden die Möglichkeiten dieser Methode umfassend anhand einer technisch bedeutenden Reaktion (elektrophile aromatische Substitutionsreaktionen) evaluiert. Um die Flexibilität einer kontinuierlichen und modularen Pilotanlage durch Echtzeit- Qualitätskontrolle zu fördern, wurde ein vollständig automatisiertes Online- NMR-Modul entwickelt. Der Einsatz eines kommerziellen Niederfeld-NMR-Geräts im industriellen Umfeld wurde durch die entwickelten Lösungen der automatisierten Datenanlyse sowie durch ein zertifiziertes Sicherheitskonzept für den Betrieb in explosionsgefährdeten Zonen ermöglicht. Neben der Überwachung der Produktqualität wurden Online-NMR-Daten in einem neuen iterativen Optimierungsansatz zur Maximierung des Anlagenertrags eingesetzt und dienten als zuverlässige Referenz für die Kalibrierung eines Nahinfrarot-Spektrometers. Für die Entwicklung einer robusten Datenauswertung der NMR-Spektren, die dem Anspruch der Flexibilität bei Produktwechseln genügt, wurden zunächst Versuche im Labormaßstab durchgeführt, um eine Datenbasis zu schaffen. In diesen Versuchen wurden die aromatischen Amine Anilin, p-Toluidin und p-Fluoranilin mit o-Fluornitrobenzol gekoppelt. Durch Zugabe einer Organolithium-Verbindung (Li- HMDS) findet ein Protonenaustausch zwischen dem primären Amin und Li-HMDS statt. Dies führt zu einer hohen Reaktionsenthalpie und instabilen Aryllithium-Verbindungen. Die Reaktionen wurden hinsichtlich anfallender Zwischenprodukte mittels Hochfeld-NMR-Spektroskopie analysiert. Nachfolgend wurden die Reaktionen sowohl im Semi-Batch-Verfahren als auch im kontinuierlichen Laborbetrieb mit Online-Niederfeld-NMR-Spektroskopie und Online- Hochfeld-NMR-Spektroskopie untersucht. Da die gemessenen NMR-Spektren besonders im aromatischen Spektralbereich hohe Signalüberlappungen der Reaktanden aufweisen, wurden chemometrische Modelle entwickelt und anhand der Hochfeld-NMR-Methode validiert. Die verwendeten Durchflusszellen für die Niederfeld-NMR-Spektroskopie wurden hinsichtlich ihrer Anwendbarkeit für quantitative Messungen im kontinuierlichen Durchfluss untersucht. Es konnte gezeigt werden, dass Messungen mit einer additiv gefertigten Keramikdurchflusszelle prinzipiell möglich sind. KW - NMR-Spektroskopie KW - Niederfeld-NMR-Spektroskopie KW - Prozessanalytik KW - Industrie 4.0 KW - Indirect Hard Modeling KW - CONSENS PY - 2019 UR - https://nbn-resolving.org/10.14279/depositonce-9404 DO - https://doi.org/10.14279/depositonce-9404 SP - 1 EP - 112 CY - Berlin AN - OPUS4-50196 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Gottu Mukkula, A. R. A1 - Kern, Simon A1 - Salge, M. A1 - Holtkamp, M. A1 - Guhl, Svetlana A1 - Fleischer, C. A1 - Meyer, Klas A1 - Remelhe, M. A1 - Maiwald, Michael A1 - Engell, S. T1 - An Application of Modifier Adaptation with Quadratic Approximation on a Pilot Scale Plant in Industrial Environment JF - IFAC-PapersOnLine N2 - The goal of this work is to identify the optimal operating input for a lithiation reaction that is performed in a highly innovative pilot scale continuous flow chemical plant in an industrial environment, taking into account the process and safety constraints. The main challenge is to identify the optimum operation in the absence of information about the reaction mechanism and the reaction kinetics. We employ an iterative real-time optimization scheme called modifier adaptation with quadratic approximation (MAWQA) to identify the plant optimum in the presence of plant-model mismatch and measurement noise. A novel NMR PAT-sensor is used to measure the concentration of the reactants and of the product at the reactor outlet. The experiment results demonstrate the capabilities of the iterative optimization using the MAWQA algorithm in driving a complex real plant to an economically optimal operating point in the presence of plant-model mismatch and of process and measurement uncertainties. KW - Process Analytical Technology KW - Online NMR Spectroscopy KW - Process Industry KW - Iterative real-time optimization KW - Modifier adaptation KW - Plant-model mismatch KW - Reactor control KW - CONSENS PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-524531 DO - https://doi.org/10.1016/j.ifacol.2020.12.685 SN - 1522-2640 VL - 53 IS - 2 SP - 11773 EP - 11779 PB - Elsevier CY - Amsterdam AN - OPUS4-52453 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kern, Simon A1 - Meyer, Klas A1 - Guhl, Svetlana A1 - Gräßer, Patrick A1 - Paul, Andrea A1 - King, R. A1 - Maiwald, Michael T1 - Online low-field NMR spectroscopy for process control of an industrial lithiation reaction—automated data analysis JF - Analytical and Bioanalytical Chemistry N2 - Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential for closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies. We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (Indirect Hard Modelling – IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union’s Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analysed by IHM with low calibration effort, compared to a multivariate PLS-R (Partial Least Squares Regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy. KW - Online NMR spectroscopy KW - Process analytical technology KW - Partial Least Squares Regression KW - Indirect Hard Modeling KW - Benchtop NMR Spectroscopy KW - Smart Sensors KW - CONSENS PY - 2018 UR - https://link.springer.com/article/10.1007/s00216-018-1020-z DO - https://doi.org/10.1007/s00216-018-1020-z SN - 1618-2642 SN - 1618-2650 VL - 410 IS - 14 SP - 3349 EP - 3360 PB - Springer CY - Berlin, Heidelberg AN - OPUS4-44847 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael T1 - Compact NMR Spectroscopy: A Versatile Tool for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - Global PAT Meeting Bayer AG CY - Berlin, Germany DA - 12.11.2019 KW - Process Analytical Technology KW - Reaction Monitoring KW - Online NMR Spectroscopy KW - CONSENS PY - 2019 AN - OPUS4-49602 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Meyer, Klas T1 - Low-field NMR spectroscopy: Applications in chemical and pharmaceutical process development N2 - Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. The talk also generally covers current aspects of high-field and low-field online NMR spectroscopy for reaction monitoring and process control and gives also an overview on direct dissolution studies of API cocrystals. T2 - Discussion Meeting Pharmaceutical Development Bayer AG Wuppertal CY - Wuppertal, Germany DA - 15.01.2019 KW - Process analytical technology KW - Low-field NMR spectroscopy KW - Online NMR spectroscopy KW - Cocrystals KW - Dissolution KW - CONSENS PY - 2019 AN - OPUS4-47201 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael T1 - Compact NMR Spectroscopy: A Versatile Tool for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - 2nd Reaction Monitoring Symposium, University of Bath CY - Bath, United Kingdom DA - 28.01.2019 KW - Process Analytical Technology KW - Process Industry KW - Online NMR Spectroscopy KW - CONSENS PY - 2019 AN - OPUS4-47271 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Kern, Simon A1 - Bornemann-Pfeiffer, Martin A1 - Guhl, Svetlana A1 - Wander, Lukas A1 - Meyer, Klas T1 - Accelerating chemical process development and manufacturing by online NMR spectroscopy N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - Symposium: Quantitative NMR Methods for Reaction and Process Monitoring (NMRPM) 2019 CY - Kaiserslautern, Germany DA - 31.01.2019 KW - Process Analytical Technology KW - Process Industry KW - Online NMR Spectroscopy KW - Data Analysis KW - Digitization KW - CONSENS PY - 2019 N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. AN - OPUS4-47297 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael T1 - Compact NMR spectroscopy: A versatile tool for automated continuous-flow production of chemicals and pharmaceuticals N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short down-times between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as , e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - GDCh-Seminar der Universität Bielefeld CY - Bielefeld, Germany DA - 17.01.2019 KW - Process analytical technology KW - Process industry KW - Online NMR spectroscopy KW - Indirect hard modeling KW - CONSENS KW - Fresenius lecture PY - 2019 AN - OPUS4-47221 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Engell, S. A1 - Gottu Mukkula, A. R. A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Maiwald, Michael A1 - Holtkamp, M. T1 - PAT‐basierte iterative Optimierung der Fahrweise eines kontinuierlichen organischen Syntheseprozesses N2 - Generell ist es Ziel der Prozessführung, Reaktions- und Trennprozesse wirtschaftlich optimal zu betreiben. Hierzu werden in großen Anlagen modellbasiere Echtzeitoptimierungsverfahren (Real-time Optimization, RTO) eingesetzt. Die Qualität der Ergebnisse der Optimierung hängt dabei entscheidend von der Güte des verwendeten Modells ab. Die Entwicklung hochgenauer Modelle ist allerdings aufwändig, was für kleine Produktionsvolumina ein wesentliches Hindernis zur Nutzung solcher Methoden darstellt. Mit Hilfe der sogenannten Modifier-Adaptation ist eine iterative Betriebspunktoptimierung auch mit ungenauen Modellen möglich, wenn Messungen der für die Bewertung relevanten Größen (beispielsweise Produktkonzentrationen im Ausgangsstrom) verfügbar sein. Für eine Lithiierungsreaktion in einem bei INVITE kontinuierlich betriebenen Reaktor wurde im Rahmen des EU-Projekts CONSENS eine solche iterative Optimierung auf der Grundlage einer Messung der Zusammensetzung des Ausgangsstroms des Reaktors mit einem Online-NMR-Spektrometer realisiert. Das Spektrometer wurde an den Betrieb in einer explosionsgefährdeten Umgebung angepasst. Es konnte gezeigt werden, dass die Messdaten genau genug sind, um darauf eine Optimierung der Produktausbeute aufzubauen. Die iterative Optimierung führt den Prozess ausgehend vom mit dem Modell berechneten Betriebspunkt schrittweise zum wirtschaftlichen Optimum für die reale Anlage. Dabei reagiert die Optimierung auch auf unbekannte Abweichungen im Prozess (wie die Zusammensetzung des Feeds) und fährt iterativ den jeweils optimalen Betriebspunkt an. Die Arbeiten wurden im Rahmen des EU-SPIRE-Projekts CONSENS, Förderkennzeichen 636942, durchgeführt. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessindustrie KW - Prozessanalytik KW - Betriebspunktoptimierung KW - Quadratic approximation (MAWQA) KW - Modellbasierte Optimierung KW - CONSENS PY - 2018 AN - OPUS4-46020 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Gottu Mukkula, A. R. A1 - Engell, S. A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Maiwald, Michael T1 - PAT-basierte iterative Optimierung der Fahrweise eines kontinuierlichen organischen Syntheseprozesses T2 - Chemie Ingenieur Technik N2 - Im Zuge der Digitalisierung der Prozessindustrie werden zunehmend modellbasiere Echtzeitoptimierungsverfahren eingesetzt, sog. „Advanced Process Control“. Mithilfe der sogenannten Modifier-Adaptation ist eine iterative Betriebspunktoptimierung auch mit ungenauen Modellen möglich, sofern zuverlässige Prozessdaten zur Verfügung stehen. Am Beispiel eines smarten Online-NMR-Sensors, der in einem EU-Projekt von der BAM entwickelt wurde, konnte das Konzept in einer modularen Produktionsanlage zur Herstellung eines pharmazeutischen Wirkstoffs erfolgreich getestet werden. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessanalytik KW - Echtzeitoptimierungsverfahren KW - Modifier-Adaptation KW - Prozess-Steuerung KW - Betriebspunktoptimierung KW - CONSENS PY - 2018 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/cite.201855233 DO - https://doi.org/10.1002/cite.201855233 SN - 0009-286X VL - 90 SP - 1237 EP - 1237 PB - Wiley-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-45902 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Kern, Simon A1 - Wander, Lukas A1 - Meyer, Klas A1 - Guhl, Svetlana A1 - Gottu Mukkula, A. R. A1 - Holtkamp, M. A1 - Salge, M. A1 - Fleischer, C. A1 - Weber, N. A1 - Engell, S. A1 - Paul, Andrea A1 - King, R. A1 - Maiwald, Michael T1 - Raw data of pilot plant runs for CONSENS project (Case study 1) N2 - In case study one of the CONSENS project, two aromatic substances were coupled by a lithiation reaction, which is a prominent example in pharmaceutical industry. The two aromatic reactants (Aniline and o-FNB) were mixed with Lithium-base (LiHMDS) in a continuous modular plant to produce the desired product (Li-NDPA) and a salt (LiF). The salt precipitates which leads to the formation of particles. The feed streams were subject to variation to drive the plant to its optimum. The uploaded data comprises the results from four days during continuous plant operation time. Each day is denoted from day 1-4 and represents the dates 2017-09-26, 2017-09-28, 2017-10-10, 2017-10-17. In the following the contents of the files are explained. KW - Process Analytical Technology KW - Multivariate Data Analysis KW - Nuclear Magnetic Resonance KW - Near Infrared Spectroscopy KW - Continuous Manufacturing KW - CONSENS PY - 2018 DO - https://doi.org/10.5281/zenodo.1438233 PB - Zenodo CY - Geneva AN - OPUS4-48063 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -