48062
2019
eng
3037
3046
14
411
article
Springer Nature
Heidelberg
1
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--
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Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals
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.
Analytical and Bioanalytical Chemistry
10.1007/s00216-019-01752-y
1618-2642
urn:nbn:de:kobv:b43-480623
1618-2650
27.05.2019
https://nbn-resolving.org/urn:nbn:de:kobv:b43-480630
Creative Commons - CC BY - Namensnennung 4.0 International
Simon Kern
Lukas Wander
Klas Meyer
Svetlana Guhl
A. R. Gottu Mukkula
M. Holtkamp
M. Salge
C. Fleischer
N. Weber
S. Engell
Andrea Paul
M. Pereira Remelhe
Michael Maiwald
eng
uncontrolled
NMR Spectroscopy
eng
uncontrolled
NIR Spectroscopy
eng
uncontrolled
Real-time process monitoring
eng
uncontrolled
Real-time quality control
eng
uncontrolled
Continuous processes
eng
uncontrolled
CONSENS
eng
uncontrolled
Data Fusion
Analytische Chemie
1 Analytische Chemie; Referenzmaterialien
1.4 Prozessanalytik
Umwelt
Chemie und Prozesstechnik
Chemische Charakterisierung und Spurenanalytik
Verlagsliteratur
Datei für die Öffentlichkeit verfügbar ("Open Access")
Wissenschaftliche Artikel der BAM
Sensorik
Bundesanstalt für Materialforschung und -prüfung (BAM)
https://opus4.kobv.de/opus4-bam/files/48062/ABC_411_2019_3037-3046_Kern.pdf
48063
2018
eng
researchdata
Zenodo
Geneva
0
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Raw data of pilot plant runs for CONSENS project (Case study 1)
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.
10.5281/zenodo.1438233
Datensatz
https://nbn-resolving.org/urn:nbn:de:kobv:b43-480623
Creative Commons - CC BY - Namensnennung 4.0 International
Simon Kern
Lukas Wander
Klas Meyer
Svetlana Guhl
A. R. Gottu Mukkula
M. Holtkamp
M. Salge
C. Fleischer
N. Weber
S. Engell
Andrea Paul
R. King
Michael Maiwald
eng
uncontrolled
Process Analytical Technology
eng
uncontrolled
Multivariate Data Analysis
eng
uncontrolled
Nuclear Magnetic Resonance
eng
uncontrolled
Near Infrared Spectroscopy
eng
uncontrolled
Continuous Manufacturing
eng
uncontrolled
CONSENS
Analytische Chemie
1 Analytische Chemie; Referenzmaterialien
1.4 Prozessanalytik
Umwelt
Chemie und Prozesstechnik
Chemische Charakterisierung und Spurenanalytik
Datei für die Öffentlichkeit verfügbar ("Open Access")
Graue Literatur
Forschungsdatensätze der BAM
Sensorik
Bundesanstalt für Materialforschung und -prüfung (BAM)
40231
2017
eng
103
103
conferenceobject
Frankfurt a. M.
DECHEMA e. V., Frankfurt
0
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Online NMR Spectroscopy for Process Monitoring in Intensified Continuous Production Plants
Process analytical techniques are extremely useful tools for chemical production and manufacture and are of particular interest to the pharmaceutical, food and (petro-) chemical industries.
Today, mainly optical online methods are applied. NMR spectroscopy has a high potential for direct loop process control. Compact NMR instruments based on permanent magnets are robust and relatively inexpensive analysers, which feature advantages like low cost, low maintenance, ease of use, and cryogen-free operation. Instruments for online NMR measurements equipped with a flow-through cell, possessing a good signal-to-noise-ratio, sufficient robustness, and meeting the requirements for integration into industrial plants (i.e., explosion safety and fully automated data analysis) are currently not available off the rack.
A major advantage of NMR spectroscopy is that the method features a high linearity between absolute signal area and sample concentration, which makes it an absolute analytical comparison method which is independent of the matrix. This is an important prerequisite for robust data evaluation strategies within a control concept and reduces the need for extensive maintenance of the evaluation model over the time of operation. Additionally, NMR spectroscopy provides orthogonal, but complimentary physical information to conventional, e.g., optical spectroscopy. It increases the accessible information for technical processes, where aromatic-toaliphatic conversions or isomerizations occur and conventional methods fail due to only minor changes in functional groups.
As a technically relevant example, the catalytic hydrogenation of 2-butyne-1,4-diol and further pharmaceutical reactions were studied using an online NMR sensor based on a commercially available low-field NMR spectrometer within the framework of the EU project CONSENS (Integrated Control and Sensing).
Processdings of 4th European Conference on Process Analytics and Control Technology (EuroPACT 2017)
4th European Conference on Process Analytics and Control Technology (EuroPACT 2017)
Potsdam, Germany
10.05.2017
12.05.2017
Svetlana Guhl
Simon Kern
Klas Meyer
Patrick Gräßer
Lukas Wander
Michael Maiwald
eng
uncontrolled
Process Monitoring
eng
uncontrolled
CONSENS
eng
uncontrolled
Online NMR Spectroscopy
eng
uncontrolled
Process Analytical Technology
eng
uncontrolled
Process control
eng
uncontrolled
Hydration
eng
uncontrolled
EuroPACT
Datei im Netzwerk der BAM verfügbar ("Closed Access")
Graue Literatur
45901
2018
deu
1236
1236
9
90
conferenceobject
Wiley-VCH Verlag GmbH & Co. KGaA
Weinheim
DECHEMA, Gesellschaft für Chemische Technik und Biotechnologie e.V.
0
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Produzieren Sie schon oder kalibrieren Sie noch? – Online-NMR-Spektrometer als Smarte Feldgeräte
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.
Chemie Ingenieur Technik
10.1002/cite.201855229
https://onlinelibrary.wiley.com/doi/abs/10.1002/cite.201855229
0009-286X
Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M.
ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen
Aachen, Germany
10.09.2018
13.09.2018
Svetlana Guhl
Simon Kern
Klas Meyer
Lukas Wander
Martin Bornemann-Pfeiffer
Michael Maiwald
deu
uncontrolled
Prozessanalytik
deu
uncontrolled
Prozessindustrie
deu
uncontrolled
Online-NMR-Spektroskopie
deu
uncontrolled
Datenkonzepte
deu
uncontrolled
Datenanalyse
deu
uncontrolled
CONSENS
Analytische Chemie
1 Analytische Chemie; Referenzmaterialien
1.4 Prozessanalytik
Umwelt
Chemie und Prozesstechnik
Chemische Charakterisierung und Spurenanalytik
Verlagsliteratur
Datei im Netzwerk der BAM verfügbar ("Closed Access")
Sensorik
41577
2017
eng
628
631
1
conferenceobject
MDPI
Basel
0
--
--
--
Strangers in the Night—Smart Process Sensors in Our Current Automation Landscape
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. Smart sensors enable concepts like self-diagnostics, self-calibration, and self-configuration/parameterization whenever our current automation landscape allows it. Here we summarize the currently discussed general requirements for process sensors 4.0 and introduce a smart online NMR sensor module as example, which was developed for an intensified industrial process funded by the EU’s Horizon 2020 research and innovation programme (www.consens-spire.eu).
Proceedings
10.3390/proceedings1040628
http://www.mdpi.com/2504-3900/1/4/628
urn:nbn:de:kobv:b43-415772
Eurosensors 2017 Conference
Paris, France
03.09.2017
06.09.2017
Creative Commons - Namensnennung
Michael Maiwald
Patrick Gräßer
Lukas Wander
Nicolai Zientek
Svetlana Guhl
Klas Meyer
Simon Kern
eng
uncontrolled
Process Monitoring
eng
uncontrolled
Smart Sensors
eng
uncontrolled
CONSENS
eng
uncontrolled
Online NMR Spectroscopy
eng
uncontrolled
Mini-plant
Analytische Chemie
Verlagsliteratur
Datei für die Öffentlichkeit verfügbar ("Open Access")
Wissenschaftliche Artikel der BAM
Bundesanstalt für Materialforschung und -prüfung (BAM)
https://opus4.kobv.de/opus4-bam/files/41577/proceedings-01-00628.pdf