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BY-NC-ND 3.0 license Open Access Published by De Gruyter December 10, 2012

Efficient and modular solutions from the Flonamic flow chemistry platforms towards modular production units: Bayer Technology Services complements its technology platform by flow chemistry

Sven Gestermann, Thomas Bieringer, Sigurd Buchholz and Joachim Heck

1 About Bayer Technology Services

Bayer Technology Services offers fully-integrated solutions along the life cycle of chemical/pharmaceutical plants – from development, through engineering and construction, to process optimization for existing plants. The Bayer subsidiary employs 2700 people worldwide at its headquarters in Leverkusen and other German locations, as well as in regional offices in Belgium, Brazil, India, Mexico, the People’s Republic of China, Russia, Singapore, the United Arab Emirates and the United States. Additional information about Bayer Technology Services is available at www.bayertechnology.com.

If higher efficiency and safety in the production of fine and specialty chemicals or active ingredients is to be strived for, flow chemistry could be the solution. Continuous flow processing is regarded as the key element for intensifying processes. Reaction conditions like temperature, mixing and stoichiometry can be controlled precisely, even locally, enabling an attractive yield improvement, reduction of energy consumption and shortening of process time. Furthermore, critical reactions using hazardous reactants, as well as very fast reactions, can run safely due to the perfect control capabilities of the flow chemistry approach.

Based on the experience of many process examples, Flonamic of Bayer Technology Services offers flow chemistry solutions. This product comprises service offerings which cover the entire development process – from the assessment of the initial idea, up to implementation in production. A key element of this approach is the application of the modular principle – during the development phase and finally for the realization of container based production units assembled from standardized modules for each process step.

2 The development process

Regardless of the starting point, be it the task to convert an existing batch process to continuous production, or the implementation of an entirely new continuous process, the Flonamic development process usually starts at a small scale in the laboratory. This first step comprises a systematic combination of chemical characterizations, including kinetic data, computational simulations and laboratory optimization trials using micro and milli process technologies (Figure 1). Based on respective modular micro or milli reaction devices, these technologies are applied to develop processes on a small scale, enabling a fast optimization of process steps like mixing, dispersing, reaction, extracting and others.

Already during this stage, the major benefits of flow chemistry are applied, like optimum control of mass and heat transfer for very fast and very exothermic or endothermic reactions, maximization yields of intermediates in consecutive reactions, opening novel process windows, e.g., by using supercritical fluids and enabling the safe handling of critical reactions due to small holdup and the best control of mixing and temperature.

The results of these optimizations could be, for instance, increased selectivity for individual process steps and boosted overall yields, but also a reduction of usage of auxiliary materials.

Figure 1 Modular MicroReaction System from Ehrfeld Mikrotechnik BTS – flexible solutions for research and development. © Ehrfeld Mikrotechnik BTS.

Figure 1

Modular MicroReaction System from Ehrfeld Mikrotechnik BTS – flexible solutions for research and development. © Ehrfeld Mikrotechnik BTS.

These feasibility or optimization studies are followed by a conceptual design study and scale up process via bench scale to pilot scale, all performed in their own technical service centers. Again, modular devices are applied at the earliest stage, retaining the identified optimal reaction parameters during transfer to the higher scale. Hence, process development is faster, and scale up risk is lower, compared to traditional process development.

Figure 2 Container based modular production unit for continuous API-production currently tested at the INVITE Research Center. © INVITE GmbH.

Figure 2

Container based modular production unit for continuous API-production currently tested at the INVITE Research Center. © INVITE GmbH.

3 The modular principle

The ultimate goal for further transfer to production scale, is to design each process step and physical and chemical operations based on standardized and well characterized modules [process equipment assemblies (PEAs)] and implement these into a container based production unit (Figure 2) [process equipment container (PEC)]. Again, the modules are designed to keep, as far as possible, the relevant reaction parameters of the modules used during the process development and scale up. This approach will significantly decrease the time to market, and lower investment costs. Furthermore, the flexibility of a plant increases considerably. If the market demand grows, further scaling can quickly be achieved by simply copying individual modules or ultimately, by adding another identical production container – the traditional scaling-up is replaced by a numbering-up of modules/containers.

Figure 3 Lonza FlowPlate MicroReactor – Ready for use in Pharma research (and pre-clinical phases). © Bayer Technology Services GmbH.

Figure 3

Lonza FlowPlate MicroReactor – Ready for use in Pharma research (and pre-clinical phases). © Bayer Technology Services GmbH.

4 The competence network

Flonamic is developed through the broad competences of the experts at Bayer Technology Services, gained in a multitude of flow chemistry projects ranging from lab scale to production. Ehrfeld Mikrotechnik BTS, a subsidiary of Bayer Technology Services, adds not only modular micro reaction systems (MMRS) suited for lab scale applications, but also larger apparatuses for pilot and production scale, namely LONZA Flow Plate (Figure 3) and Miprowa reactors based on micro reaction principles, thus eliminating scale up risks.

Also the INVITE Research Center in Leverkusen is part of the Flonamic network. This company, which was officially inaugurated in 2011 by Bayer Technology Services and the Technical University of Dortmund, offers a highest level technical infrastructure and core competencies for developing and demonstrating new production concepts. One concept is the realization of container based modular production units, currently developed within the European Union sponsored F3 Factory research project. This €30 million multi partner project aims to develop faster and more flexible manufacturing processes for the chemical industry.

5 The benefits

  • Flonamic is a one stop shop for flow chemistry, from the assessment of the first idea, to a container based modular production-scale plant

  • Process development is faster compared to traditional process development

  • Standardized, modular process units ensure fast and robust scalability

  • Investment risks are shifted to early phases of process development

  • Investment and running production costs are lower

6 Case study – high quality intermediate

Within the F3 factory project, Bayer Technology Services validated the modular approach. As the first industrial case study to be demonstrated in the INVITE Research Center, the chemical reaction steps of an API-production have been implemented into a container based production unit (PEC) based on standardized PEAs. By the end of 2012, Bayer aims to demonstrate the continuous processing of this high quality intermediate in the PEC at INVITE. This will help pave the path for the introduction of the new Flonamic technologies, production concepts and process equipment solutions for the pharmaceutical manufacturing sector.

Contact:

Dr. Sven Gestermann

Tel.: + 49 214 30–80090

E-mail:


Corresponding author: Sven Gestermann, Bayer Technology Services – CPM-TPM, Building K9, 51368 Leverkusen, Germany

Published Online: 2012-12-10
Published in Print: 2012-12-01

©2012 by Walter de Gruyter Berlin Boston

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