F3 Factory Case Study: High-Volume, Biomass-based Intermediate Chemicals

In its F³ Factory case study Arkema sought to demonstrate both the technical and economic viability of producing high volume intermediate chemicals in modular, medium scale plants. Working in collaboration with the Process Design Centre, Ehrfeld, Coatex and three academic partners, CNRS Nancy, TU Dortmund and the Institute of Catalysis & Surface Chemistry PA, Poland, this project is exemplified by the production process for acrylic acid and its derivatives from biomass-based glycerol.

Chemical intermediates produced in high volumes (hundreds of thousands to several million tonnes per year) are traditionally manufactured in large, dedicated, continuous world-scale plants. These high-volume, highly optimised plants benefit from economy of scale, for example in terms of capital expenditure per unit of product, the efficient use of raw materials and/ or energy integration.

However, these plants require large upfront investment and significant development time and effort to build. They also lack flexibility in terms of quick adaptation to changing market conditions and the introduction of new or more efficient technologies.

The F³ Factory concept for decentralised, modular, continuous, medium-scale plants is therefore focused on the development of smaller and more flexible production units that can be located, for example, closer to raw material suppliers or downstream users.

The state-of-the-art process for producing acrylic acid and its derivatives starts with fossil-based propylene. The Arkema case study sought to develop a new ‘greener’ and more cost-effective production process (see below) that begins with biobased glycerol: a widely available green by-product of the oleochemical sector and biodiesel production.

Medium-scale plants
To compete with state-of-the-art world-scale processes, the new F³ Factory process needs to be refined and optimised to provide the most economic alternatives. Process Design Centre (PD) developed a methodology for the design of optimised, complex, medium-scale plants by adapting conceptual process designs to fit with the new F³ Factory concept. This systematic approach is an iterative ‘whole process design’ which comprises:

• black-box modelling to establish an initial idea of the process steps
• selection of possible function or tasks
• selection of unit operations capable of providing the required performances (within the F³ Factory approach, unit operations that are more compact or easy to number up, are preferred)
• integration into a detailed flow-sheet and mass balance

Production challenges to innovative solutions
Replacing fossil fuel feedstock with biobased feedstock leads to several challenges:

• the impurity profile of the new feedstock needs to be managed
• any varying quality issues in the raw material
• faster deactivation of catalyst can occur in some cases and must be addressed, while maintaining high production yields
• a biobased process is competitive from an economical and environmental point of view but only if the process is not too energy intensive

Whole process design evaluation, focusing on the systematic examination of alternatives allowed Arkema to select processes with low emissions and high energy integration. Parallel laboratory and process work successfully optimised the process, taking into account specific conditions for reaction and purification requirements.

As part of the development work on intensified chemical reactors, Arkema developed and patented innovative solutions to handle faster deactivating catalysts with a very low number of reactors. Process intensification was also implemented by combining reaction and distillation in a single piece of equipment for acrylate ester production.

Looking at downstream processes, the case study focused on optimised purification sequences that combine a set of distillation and crystallisation steps.  As part of this activity, a new process with a reduced number of distillation columns was patented. Intensified crystallisation apparatus for melt crystallisation's using milli/microstructured devices was also developed and patented.  Breaking azeotrope with membrane was also introduced to reduce the amount of equipment required and energy consumption.

Validation
In conducting the validation studies for this case study, Arkema discovered and patented a new process for the selective chemical elimination of propanal in acrolein which simplifies the purification scheme for acrylic acid.

Two pilot plants for validation of the F³ Factory concepts, at a production scale of several kilogrammes per hour have been established at Arkema and TU Dortmund and biobased acrylic acid has been successfully polymerised at Coatex.

Whole process design (optimising the whole process as opposed to individual unit operations) and process intensification were key success factors in establishing a new process for the production of an intermediate chemical from a new biobased feedstock.

Learning from this case study suggests that the development of modular, medium-scale production (row housing) can deliver production flexibility and reduce financial risk when considering production needs for a new or growing market.

More information
For more information visit the F3 Factory Project website or contact Jean-François Devaux at Arkema.

F3 Factory Case Study: Continuous Processing for Pharmaceuticals

This AstraZeneca led case study for in the F³ Factory project focused on the development of a proof of principle concept for the flexible, continuous production of pharmaceutical development materials for toxicological and clinical studies.  Working with academic partners KTH Institute of Technology, Denmark Technical University (DTU), Newcastle University and Karlsruhe Institute of Technology (KIT), as well as industrial partner Britest, the project developed and validated a new generic transformation methodology for the formation of pharmaceutical intermediates.

One of the biggest challenges facing the international pharmaceutical industry is the ability to offer a flexible response to the production of new materials for toxicological studies (both in vivo, in vitro).

The F³ Factory approach to providing a “one size fits most” process synthesis for the production of intermediates for ‘Campaign 2’ material offers an opportunity to build a faster and more flexible response to this requirement by:

• reducing the cost of process development

• increasing throughput and improving robustness

• increasing manufacturing flexibility

Mindset barriers
New transformation methodology

• development of a novel isolation technology (in conjunction with KIT) to isolate solid material, evaporate solvent and achieve uniform solid beads

• development of a new continuous, micro-structured reactor (in conjunction with KIT - see image of a microstructured reactor plate below) capable of handling dispersed solid catalyst and a slurry feed, thus removing the need for fixed bed technology

Continuous manufacturing technologies for work-up in final stage active pharmaceutical ingredient synthesis are also of major interest to AstraZeneca.

A key barrier to overcome in this context was a mindset issue of “we’ve always done things this way, so why change” and/or “if it isn’t broke why fix it?” In recent years there has been some progress in this respect across the pharmaceutical industry but there is more progress to be made.

There are also Quality Assurance issues to overcome with regard to continuous processing versus batch manufacture – for example. how to define ‘in specification’ and ‘out of specification’ material.

Nitro reductions were selected to test the F³ Factory concept with transfer / catalytic hydrogenation identified as key options. A generic process and Substrate Adoption Methodology (SAM) were developed with DTU and Britest to enable more effective screening of molecules before they evaluated in the reactor.

A Risk Assessment Methodology (RAM) was also developed by the University of Newcastle to understand the value of the F³ Factory approach, not only in economic terms, but also in terms of reducing business risk in general.  For AstraZeneca, the RAM provided a structured approach and useful visualisation of risk assessment processes undertaken as a matter of routine.

Key technical features of this project included:

Project results

Reactions undertaken in AstraZeneca’s Large Scale Laboratory in the UK fully validated this new transformation methodology. A semi-modular production unit, with the ability to install different PEAs (process equipment assemblies) depending on the chemistry required, were installed successfully. AstraZeneca is now evaluating this new production unit for drug projects and obtaining better yields (mid 70% continuous versus 50% batch).

AstraZeneca recognises the value of collaborating in European Commission Framework projects as an important and practical means of supporting and enhancing its own internal research and development activities. It recognised at an early stage that the aims and objectives of the F³ Factory project aligned closely with its own research objectives and that the collaborative aspects of this large demonstrator project could lead to step-change process innovation in the development of new pharmaceutical compounds.

More information

For more information visit the F3 Factory Project website or contact Anil Mistry at AstraZeneca.

F3 Factory Case Study: Water Soluble Speciality Polymers

The Europoly project case study saw Rhodia-Solvay and BASF collaborate to design and build a continuous, multi-product pilot plant to demonstrate the technical and economical viability of the F³ Factory concept for the production of solution polymers.

Water soluble synthetic polymers are used in a wide range of markets and applications with production of water soluble polymers in Europe estimated to be greater than 750 000 tonnes per annum with a market value of over €2.5 billion.

The project was supported by academic partners, CNRS Nancy and TU Dortmund, where feasibility studies were undertaken on two model polymer systems:

• acrylic acid-based copolymer (CNRS & Rhodia-Solvay)
• homo-polymerisation of acrylic acid and copolymerisation of acrylic acid with a second monomer with extremely different copolymerisation parameters (TU Dortmund and BASF)

Polymer challenges

A key challenge in polymer production is to manage the high heat production rate during radical polymerisation reactions. This is particularly difficult to manage in conventional large-volume stirred batch reactors due to heat transfer limitations related to the low surface area-to-volume ratio of the reactor vessel. These batch processes are usually run in fed-batch mode with a long cycle time and semi-continuous addition of reactants, such as monomers and initiators, to control the extent of the exothermic reaction.

The Europoly project evaluated the advantages of a new continuous, intensified process technology that could deliver the required product characteristics with a heat transfer capability more appropriate for the reaction. 

In other words the project looked to adapt the process to the product rather than the traditional approach of adapting the product to the process!

In transferring production from batch to continuous mode, based on process intensification and standardised modules, the project team targeted improved sustainability and competitiveness objectives through:

• increased productivity for the same investment cost
• reduced fixed costs through lean processes and productivity enhancements
• improved process robustness by replacing batch reactors used to manufacture multiple products with continuous, product-optimised processes
• improved product uniformity resulting from continuous process control in place of batch production (i.e. to eliminate batch-to-batch deviations in product quality)

Radical intensification

A key success of the project was the development of a scalable mixer-heat exchange tubular reactor concept using Fluitec static mixer technology. This reactor is equipped with a novel internal cooling system element that controls heat production during the process.

Intensive use of kinetic data in millifluidic devices and rheokinetic data from lab-scale batch reactors, that were tested during the validation stage, was key to the successful design of the intensified continuous reactor used in the demonstration stage. The continuous polymerisation process was monitored by:

• in-line spectroscopy with mid-infrared at TU Dortmund
• Raman spectroscopy at CNRS, Nancy 

Lab-scale evaluation at TU Dortmund and CNRS, Nancy successfully validated the transfer of (co)polymerisation reactions from batch to continuous operation for both products. Process intensification factors from 10 to 100 were achieved with products in specification in relation to:

• residual monomer content
• molecular weight

Project achievements

The successful transfer of the copolymerisation reactions to continuous flow was achieved. 

The new process was designed to fit in a half-sized standard process equipment container (PEC) that was initially fabricated at Rhodia-Solvay’s site in France. The completed PEC was transported to (see above) and installed at the INVITE Research Centre in Leverkusen, Germany during quarter two of 2013 and the process was successfully demonstrated.

The Europoly case study highlighted the overall F³ Factory concept of ‘fast, flexible and future’ by achieving:

• Fast: The continuous operation of an intensified process.
• Flexible: The use of the same PEC and PEAs (process equipment assemblies) for two different polymers.
• Future: By using modular technology in a multi-product environment i.e. use of the same PEC and PEAs.

More information

For more information visit the F³ Factory website or contact Patrick Ferlin at Rhodia or Christian Schwede at BASF.

F3 Factory Case Study: Continuous Production of Chemical Intermediates

For its F³ Factory industrial case study Evonik Industries AG focused on demonstration of the flexible, continuous production of intermediate chemicals. Working with academic partners TU Dortmund, TU Eindhoven and Newcastle University the project looked at the development and validation of a generic methodology for modularised production plants of medium scale for example for fence-to-fence applications in emerging markets.

As a global leader in specialty chemicals production Evonik Industries AG’s products are used in a wide variety of high end application areas including pharmaceuticals, agrochemicals, paints and coatings, paper, plastics, personal care and hygiene, adhesives and sealants. Innovative production strategies in these fields are a key focus of Evonik’s research and development projects.

Typical intermediates include those produced in highly exothermic reactions which suffer from limited heat and mass transfer capabilities. Present reactor technologies are complex and unique for each product and plant and are mainly economic only in world-scale capacities: in production facilities producing more than 100 000 tonnes per annum.

The F³ Factory approach can help Evonik become more flexible in production capacities, enable the use of different feed qualities and allow faster scale-up procedures to reduce time-to-market. Depending on the specific reactions investigated, step changes in production are expected including increased production effectiveness, energy savings and lower investment costs amongst many others.

Modular production technology 

Achieving the challenging goals of the F³ Factory project can only be reached through innovative process intensification technologies. For the Evonik case study, two different technologies were investigated:

• structured catalyst packing
• jet-loop reactor with integrated “cold” membrane separation

Both technologies focused on the intensification of mass and heat transfer as well as simplification of the specific chemical reactor design.

The first reactor technology required new catalyst structures which could be implemented as “plug-in” technology in existing plants. In the near future these could also be used in modularised new reactor concepts.

Simpler reactor construction will reduce investment costs and enable greater standardisation of reactor technology. Parallelization of this technique offers high potential for more flexibility in production capacity to support future market growth.

The second reactor technology is designed for highly exothermic liquid-gas reactions. Innovation in catalyst development requires an improved reactor concept to enable the heat management and mixing requirements necessary to maximise catalyst efficiency.

For the F³ Factory modular approach a parallel jet-loop set-up was envisioned, which combines high mass transfer performance and efficient heat management through the jet-loop principle with an integrated membrane separation for catalyst retention. The basic set-up is shown below.

This modular approach can easily be adapted to varying production scenarios by adding additional reactors or membrane Process Equipment Assemblies.

The benefits of this approach are:

• reduced investment costs through standardised and easily scaleable reactor equipment
• reduced operating costs due to maximised space-time yield and integrated heat management
• high selectivities due to low heat gradients and ideal mixing
• improved catalyst lifespan due to separation under process conditions

Following process development the production unit was transferred to the modular, container-based concept developed within the F³ Factory project.  This hydroformylation process in a jet-loop, with an integrated membrane separation, was then successfully demonstrated in the F³ Factory backbone facility at the INVITE Research Centre in Leverkusen, Germany.

With successful demonstration of the intensified technologies in a modular production environment, the basis of a possible new production concept has been realised.  The concept will now be further developed and optimised.

Validation and demonstration
Partial oxidation, epoxidation and hydroformylation were selected as example reaction classes for the case studies.

In cooperation with the University of Newcastle and TU Dortmund, software tools have been developed to evaluate the economic and technological aspects of applying this F³ Factory approach. With the help of the universities, models have been set-up to optimise operation conditions and operation control aspects.

The applied process intensification technologies have been proven to operate successfully at both lab and pilot scale levels. Design and engineering of modularised process equipment assemblies and process equipment containers for the hydroformylation reaction was completed successfully and the modularised hydroformylation process was successfully demonstrated at INVITE.

Project contact information:

For more information visit the F3 FactoryProject website or contact Dr. Frank Stenger at Evonik.

Save the Date: SusChem Horizon 2020 Brokerage

With the news that SusChem has been recognised as a European Technology Platform 2020 (ETP 2020) it is now time to start preparing for the new European framework programme for Research and Innovation - Horizon 2020 – that will start on January 1, 2014. And, as ever, SusChem is planning to take a leading role in enabling its stakeholders to participate fully in the initiative’s ambitious collaborative research programme.

To help SusChem stakeholders to prepare for forthcoming Horizon 2020 developments and future calls, SusChem is organising a "Pre-Brokerage" Event on 23 October at the Crowne Plaza Le Palace, Rue Gineste 3 in Brussels.

This will be the perfect occasion to commence your Horizon 2020 preparations and interact with future research partners!

Key activity
As an ETP 2020 one of SusChem’s key activities is to encourage industry participation in Horizon 2020 and helping widen participation and build capabilities within Member States through cooperation with networks and partnerships. The 23 October event will mark the start of SusChem’s engagement in the implementation of Horizon 2020.

For more information on the SusChem Pre-Brokerage event and our activities around strategic research and innovation in sustainable chemistry for Europe, please contact the SusChem secretariat.

SusChem is an ETP 2020!

Coinciding with the official publication on Friday (12 July 2013) of a European Commission document on a 'Strategy for European Technology Platforms: ETP 2020' SusChem has been confirmed as a European Technology Platform for Horizon 2020. The ETP 2020 strategy seeks to maximise the impact of European Technology Platforms (ETPs), such as SusChem, on Europe’s competitiveness and sustainability.

This important achievement was conveyed in a letter from the Director-General of the European Commission’s DG Research and Innovation, Robert-Jan Smits, to SusChem Chairman Dr Klaus Sommer, and SusChem Coordinator Dr. Jacques Komornicki.

“Since 2004 SusChem has been making a very significant contribution to European sustainable chemistry research and innovation programmes. SusChem has been a pioneer in terms of stimulating cross-sectoral and value chain initiatives and we look forward to continuing and enhancing our contribution through Horizon 2020,” said Jacques Komornicki.

“SusChem’s involvement in FP7 has been profound for sustainable research in Europe,” said Dr. Klaus Sommer. “Now we are looking forward to truly fulfil our potential also in the area of innovation through Horizon 2020 especially with our involvement in major EU programmes such as public- private-partnerships (SPIRE and BRIDGE), future emerging technologies and key areas such as water, raw materials, key enabling technologies and skills. We are ready to make a real impact economically and ecologically all over Europe through projects that generate great research results and true innovations to bridge the gap between invention and relevant business success.”

ETP 2020 landscape
A new landscape of Commission recognised ETPs is now in place following an assessment against revised criteria for recognition defined in the ETP 2020 Strategy (see below).

ETPs span a wide range of technology areas and many, like SusChem, have played an important role in developing joint visions, setting Strategic Research and Innovation Agendas and defining research priorities that have been pursued in FP7.

As part of Horizon 2020 ETPs will:

• Develop strategies and provide a coherent business-focused analysis of research and innovation bottlenecks and opportunities related to societal challenges and industrial leadership actions
• Mobilise industry and other stakeholders within the EU to work in partnership and deliver on agreed priorities
• Share information and enable knowledge transfer to a wide range of stakeholders across the EU.

The objectives of ETPs will be achieved through a broad portfolio of activities many of which SusChem has been pursuing for a number of years. These include:

• Developing Strategic Research and Innovation Agendas
• Encouraging industry participation in Horizon 2020 and helping widen participation and build capabilities within Member States through cooperation with networks/partnerships in Member States
• Identifying opportunities for international cooperation and developing the necessary understanding to facilitate future collaboration
• Providing networking opportunities including with other ETPs to address cross-sectorial challenges and promote the move towards more open models of innovation
• Facilitating the formation of new partnerships that utilise ETP expertise.

Revised criteria
To date, one of the main benefits of the ETPs has been their ability to provide coherent, strategic advice. Moving forward, the Commission has defined criteria that must be met for the recognition of an ETP. These criteria are:

• Alignment with Europe 2020 priorities and objectives – this could either be in terms of their ability to effectively address a Horizon 2020 societal challenge and/or develop sustainable industrial capability in a priority sector or emerging area;
• Scale of the market opportunity – this must represent a sizeable proportion of a current or potential future market and be seen to contribute to the global value chain benefiting Europe;
• EU added value - the EU's capacity, capability and skill-base to research, develop and exploit the technologies and/ or innovations in the proposed field;
• Transparency and openness – the ETP must be representative of its field, transparent in its activities and be open to new members;
• Scope – the extent to which the ETP reaches beyond a niche area and fosters interdisciplinary and cross-sector work without duplication;
• Leverage – the level of engagement and commitment of industry and Member States to the ETP, the ETPs ability to deliver on its proposed agenda and its collaboration with other ETPs on achieving common objectives.

European Technology Platforms are industry-led stakeholder fora that develop short to long-term research and innovation agendas for action at EU and national level that can be supported by both private and public funding. SusChem was formed in 2004 as one of the first ETPs and has consistently been a model example of the format.

ETPs will be a significant part of the external advice and societal engagement effort that the Commission needs to successfully implement Horizon 2020. ETPs are a key element in the European innovation ecosystem and an essential element to transform Europe into a true Innovation Union.

The Commission is planning to hold a cross-ETP workshop in the near future to discuss, amongst other issues, how the new ETP 2020 strategy can be best implemented and how relationships between the ETPs and the Commission can be further strengthened.

BIO-TIC Regional Events

During the Autumn the BIO-TIC FP7 project is organising a number of regional workshops throughout Europe. The aim of the BIO-TIC project is to develop an integrated roadmap and action plan for the successful development of industrial biotechnology in Europe. And the workshops are your opportunity to input your thoughts on how to overcome barriers to innovation in industrial biotechnology. 

Input from the workshops will be crucial in helping BIO-TIC develop an action plan which best addresses the needs of European stakeholders in this exciting growth area. Six regional workshops have recently been announced:

Poland: This free one-day workshop discussing issues surrounding the uptake of industrial biotechnology in Poland will be held on Thursday 19 September at Technopark, Łódź and is a satellite event to ‘The Second International Congress on Bioeconomy’ which is happening at Łódź on Friday 20 September. If you are interested in participating, please register online or contact Claire Gray at EuropaBio.

Spain: This free one-day workshop discussing issues surrounding the uptake of industrial biotechnology in Spain will be held on Wednesday 25 September at the Palacio de Congresos de Toledo.

Nordic Countries: This workshop discussing issues surrounding the uptake of industrial biotechnology in Nordic countries will be held on Thursday 3 October at Finlandia-talo, Helsinki.

Germany: This workshop discussing issues surrounding the uptake of industrial biotechnology in Germany will be held on Thursday 10 October in Hannover, Germany.

Italy: This workshop will discuss issues surrounding the uptake of industrial biotechnology in Italy. The workshop will be held on Thursday 24 October in Naples, Italy.

UK and Ireland: This free workshop discussing issues surrounding the uptake of industrial biotechnology in the UK and Ireland will be held on Tuesday 19 November in London.

For more information on the workshop series, please keep an eye on the BIO-TIC project website or contact BIO-TIC coordinator Claire Gray at EuropaBio for more information about registration and the workshop programmes.

What is BIO-TIC?
The BIO-TIC FP7 project is the largest network dedicated to industrial biotechnology and the bioeconomy. Launched in September 2012, BIO-TIC is a three-year project offering “a solutions approach” centred on a solid road mapping exercise involving a broad stakeholder base from industry, knowledge organisations, governments and civil society.

The regional workshops are part of a series of stakeholder workshops that will take place at national and European level to reach a comprehensive view on the solutions BIO-TIC can offer to accelerate market uptake of industrial biotechnology and the development of the bioeconomy. The final aim of the project will be to draw up a blueprint document with a comprehensive set of policy recommendations for overcoming the identified innovation hurdles within a selection of European business and societal opportunities.

You can find out more about the project at the BIO-TIC website and there is an active BIO-TIC Linked-In group that is open to anyone interested in the transformative potential of industrial biotechnology.

The project is coordinated by EuropaBio, where Antoine Peeters is BIO-TIC Project.