Leverkusen, Germany


Leverkusen, Germany
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Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2009-3.2-1 | Award Amount: 15.99M | Year: 2010

The SYNFLOW vision is the paradigm shift from batch-wise large volume processes in pharmaceuticals, fine chemicals and intermediates production comprising many separate unit operations towards highly integrated but yet flexible catalytic continuous flow processing. For this purpose, SYNFLOW develops a unique integrative approach combining molecular understanding of synthesis and catalysis with engineering science in process design and plant concepts, aiming at an efficiency breakthrough in process development and operation. The SYNFLOW mission is to overcome the traditional way of linear process development providing individual solutions for specific products, and to demonstrate the technological, economic and ecological superiority of truly designing processes by application of advanced chemical and engineering knowledge. The SYNFLOW concept is based on the definition of generic challenges with industrial relevance, represented by Case Studies provided by the industrial consortium members. Catalyst development, studies of the underlying chemical target transformations (synthetic methodology), tailored reaction engineering, conceptual process design and process evaluation interact closely in order to substantiate the SYNFLOW vision. Its success will be demonstrated on a relevant production scale as a reference for the entire European Chemical Industry. The SYNFLOW consortium brings together major industrial producers from the Pharmaceuticals, Fine Chemicals and Intermediates sectors, providers of process technology and technical catalyst supply. A number of high-ranked academic partners ensures the availability of comprehensive expertise for the suggested Case Studies. Dissemination of the results is guaranteed by the participation of DECHEMA and Britest. SYNFLOW presents a holistic approach to central challenges of the European Chemical Industries and therefore a highly promising candidate to fulfill the crucial issues of the NMP-2009-3.2-1 call.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2008-3.2-1 | Award Amount: 29.36M | Year: 2009

The F3 consortiums vision is that the EUs chemical industrys competitive position would be strongly enhanced if it could operate modular continuous plant (F3 plant) which combines world scale continuous plant efficiency, consistency and scalability with the versatility of batch operation. Our project will deliver such a radically new production mode based on: a) Plugandplay modular chemical production technology, capable of widespread implementation throughout the chemical industry. This technology uses generic backbone facilities designed for rapid interfacing with standardized process equipment containers (PEC). The PEC house process equipment assemblies (PEA) composed of intensified process equipment for fast, flexible future chemical production b) Holistic process design methodology applying process intensification concepts and innovative decision tools. This will accelerate process development and provides a substantial reduction in energy consumption, raw material usage and plant volumes. Our consortium of leading academic & research institutions and 7 major synthetic chemical producing industrial companies has 3 main goals: 1. To prove the technical feasibility of the F3 mode of manufacturing by building and operating a 0.1 to 30 kg/hr demonstration facility, 2. To demonstrate that operation of F3 plant will be more economical, ecoefficient and more sustainable than conventional production modes like large scale continuous or small to medium scale batch processing. 3. To drive a step change in the technology available to EU chemical production and engineering companies by designing intensified equipment for reaction and down stream processing, dissemination of standards for plug and play modular plant and providing open access to the backbone facility Our estimates indicate that the F3 concept will generate additional new business and will save 3.75 billion euro when existing products change to the F3 mode of manufacture.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SPIRE-01-2014 | Award Amount: 6.00M | Year: 2015

Intensified continuous processes are a key innovation of the last decade for the production of high quality, high value and customer-specific products at competitive prices in a sustainable fashion. To realize the potential of this technology, key steps must be made towards long-term stable, tightly controlled and fully automated production. The goal of the CONSENS project is to advance the continuous production of high-value products meeting high quality demands in flexible intensified continuous plants by introducing novel online sensing equipment and closed-loop control of the key product parameters. CONSENS will focus on flexible continuous plants but the results will be transferable also to large-scale continuous processes. The research and development is driven by industrial case studies from three different areas, spanning the complete value chain of chemical production: complex organic synthesis, speciality polymers, and formulation of complex liquids. Innovative PAT technology will be developed for online concentration measurements (mid-resolution process NMR), for the online non-invasive measurement of rheological properties of complex fluids, and for continuous measurements of fouling in tubular reactors. New model-based adaptive control schemes based on innovative PAT technology will be developed. The project results will be validated in industrial pilot plants for all three types of processes, including validation in production containers that have been developed in the F3 Factory project. Further, methods for sensor failure monitoring, control performance monitoring and engineering support for PAT-based solutions will be developed. The exploitation of the new technologies will be facilitated by a tool for technology evaluation and economic impact assessment. A Cross-sectorial Advisory Board supports the transfer of PAT technologies and adaptive control to neighboring sectors of the European processing industry.

Bramsiepe C.,TU Dortmund | Krasberg N.,INVITE GmbH | Fleischer C.,INVITE GmbH | Hohmann L.,TU Dortmund | And 2 more authors.
Chemie-Ingenieur-Technik | Year: 2014

Process and plant design is associated with long lead times from first planning to plant commissioning. Methods to reduce lead time in chemical engineering process and plant design are reviewed. Experiment-based process design methods for small-scale production will be discussed as well as recent approaches for module-based plant design. For both, the required information technologies will be discussed, and an overview will be given about suitable and available software solutions. Finally, an innovative approach to modularization for small-scale continuous container processes will be presented. © 2014 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.

Klutz S.,Invite GmbH | Lobedann M.,Invite GmbH | Bramsiepe C.,Invite GmbH | Schembecker G.,TU Dortmund
Chemical Engineering and Processing: Process Intensification | Year: 2016

Due to the evolving biopharmaceutical market, small scale and flexible production processes for continuous antibody manufacturing become more important. Consequently, various continuously operated processing steps like perfusion fermentation or continuous chromatography have been developed. However, no continuously operated viral inactivation at low pH value is available so far. In this article, the coiled flow inverter (CFI) is identified as a suitable reactor for this application and two different design approaches are presented. The logarithmic reduction value (LRV) approach targets at the same LRV in the continuous viral inactivation when compared to current batch operation. The minimum residence time (MRT) approach guarantees a residence time for all molecules entering the continuous viral inactivation of at least the inactivation time of the batch inactivation step. The viral reduction value and the monomer loss during inactivation are characterized for each design approach. Moreover, a linear regression model is developed, which predicts the Bodenstein number as a function of two CFI design parameters under defined boundary conditions. This model allows designing the CFI according to the inactivation time and the chosen design approach. © 2016 Elsevier B.V.

Rieks M.,Invite GmbH | Bellinghausen R.,Bayer AG | Kockmann N.,TU Dortmund | Mleczko L.,Bayer AG
International Journal of Hydrogen Energy | Year: 2015

Dry reforming of methane (DRM) is an interesting process as it allows for CO2 utilization and production of CO-richer syngas compared to methane steam reforming (SMR). Due to the endothermic reaction, reformer concepts suitable for high heat fluxes have to be developed. In this work, we therefore experimentally investigate a novel electrically heated reformer. Heating elements consisting of a FeCrAl alloy are coated with a LaNi0.95Ru0.05O3 catalyst at different washcoat thicknesses. The effects of different operating parameters on the performance of the DRM reaction and the reverse water gas shift (RWGS) reaction are evaluated. A combined operation of dry and steam reforming is also investigated. The results show a maximal CH4 conversion of 29.4% using one heating element at 900 °C. The H2/CO ratio in the gas can be varied between 0.4 and 12.3 by combining steam and dry reforming. However, CH4 conversion decreased when steam is added. © 2015 Hydrogen Energy Publications, LLC.

Holtmann L.,Invite GmbH | Lobedann M.,Invite GmbH | Magnus J.,Bayer | Schembecker G.,TU Dortmund
European Pharmaceutical Review | Year: 2016

Continuous production of monoclonal antibodies (mAbs) using disposable equipment will be a major future trend. However, continuous viral clearance is often not considered in the ongoing discussion'. This article provides an overview of current viral clearance techniques and the challenges of their applicability within continuous processes and disposable equipment. It answers the question of whether viral clearance in general inhibits fully continuous processing of mAbs within disposables. Several existing techniques for batch processes for mAb and plasma product production are possibilities for continuous viral clearance. UV-C treatment and viral filtration are commercially available alternatives based on batch processing. Therefore, a further adaptation towards continuous process conditions would be beneficial. The two platform process viral clearance steps - low pH viral inactivation and viral filtration - have already been implemented into a fully continuous miniplant. Although many techniques need further research and/or adaptation from the vendor's site, viral clearance does not fully inhibit continuous and disposable production of mAbs. © 2016 Russell Publishing Limited. All rights reserved.

Klutz S.,Invite GmbH | Kurt S.K.,TU Dortmund | Lobedann M.,Invite GmbH | Kockmann N.,TU Dortmund
Chemical Engineering Research and Design | Year: 2015

For chemical reactions, which require residence times of several hours, enhanced heat transfer, or narrow residence time distribution (RTD), good radial mixing combined with poor axial mixing in laminar flow regime has long been desired by industry and R&D. The main goal of this work is to obtain the narrowest RTD curve in a continuously operated reactor at Reynolds numbers smaller than 100. By using a stepwise method the most promising reactor type was chosen to meet the requirements. Design parameters of this reactor, the coiled flow inverter (CFI), were characterized and their effects on RTD were experimentally investigated. Design of CFI includes several straight helix modules, where the tubular reactor is coiled around a coil tube. After each straight helix module, the coil direction is changed by a 90°-bend. As a starting point for designing a CFI reactor for specific applications, the "best performance" design space diagram was investigated. Regarding narrowing RTD, the diagram gives the user the design space for the CFI reactor, which leads to the best performance. The most significant design parameter regarding a narrow RTD was experimentally determined as number of bends. By using a CFI design consisting of 27 bends at volume flow rate of 3. mL/min, which corresponds to Reynolds number of 24 and mean residence time of 2.6. h, a Bodenstein number over 500 was achieved. Beside its narrow RTD behavior, CFI is a compact and cost-efficient reactor concept, which is flexible to scale-up and implement for different processes, even for single-use applications. © 2015 The Institution of Chemical Engineers.

Bieringer T.,INVITE GmbH | Buchholz S.,Bayer AG | Kockmann N.,TU Dortmund
Chemical Engineering and Technology | Year: 2013

Modular continuous production concepts are already successfully applied in research, development, and piloting of a series of chemical compounds in the markets of fine chemistry and pharmaceutical products. Besides, first case studies for the application of those concepts in industrial scale are reported. Current European research projects focus to proof their applicability in a broader range. The elaborated know-how will be commercially used in a franchise between BTS, INVITE, Ehrfeld Mikrotechik BTS, and further partners in the product Flonamic®. One core element of these production concepts are micro- and milli-structured devices assisting continuous-flow processes due to their superior transport characteristics and small holdup. In small-scale production concepts, these special devices have to be considered together with conventional technology. The platform concept developed by TU Dortmund University for chemical manufacturing simplifies the scale-up process from lab to container scale and beyond on different levels in flow rate, temperature, or other process conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed | Invite GmbH, TU Dortmund and Bayer AG
Type: | Journal: Journal of biotechnology | Year: 2015

To maintain or strengthen their market position, biopharmaceutical producers have to adapt their production facilities to a drastically changed market environment. Contrary to currently used large scale batch-wise operated production facilities, where stainless steel equipment is widely applied, small scale and flexible production processes are desired. Consequently, the concept of the biofacility of the future has been developed, which combines the attributes fast, flexible, small, inexpensive and sustainable. Four design principles build the facilitys basis and are presented within this work: continuous processing, 100% single-use equipment, closed processing and adopting the ballroom concept. However, no publication presents a completely continuously operated platform process for the production of monoclonal antibodies up to now. Therefore, this work establishes the proof of concept regarding continuous antibody manufacturing. A pilot plant for the production of monoclonal antibodies has been built 100% in single-use equipment. It was operated fully continuous and automated in the upstream and the downstream part. The concepts that allow continuously operating the pilot plant are presented within this work, i.e., continuously operated filtration, continuously operated viral inactivation, continuously operated chromatography and a continuously operated formulation. Analytics showed that the produced product was within specification limits of industrial bulk drug substances.

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