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Performance Boost for Enzymatic Oxidations by means of Process Intensification and Continuous Flow Processing 

O2-dependent biotransformations are promising for chemical synthesis. Their development to the level of efficiency required in fine chemical manufacturing has proven difficult however, due to thermodynamic and kinetic limitations when supplying O2 to the enzymatic reaction creating a complex bottleneck on conversion efficiency using batch technology at atmospheric pressure.

Process intensification for oxidative O2-dependent biotransformations is a promising tool using a batch-to-conti approach. In a cooperation between the Austrian Center of Industrial Biotechnology (ACIB) and Microinnova Engineering GmbH it was shown that process intensification applying continuous flow technology offers a comprehensive solution. continuous flow reactor using up to 34 bars enables biotransformations to be conducted in a single liquid phase. Increased enzyme activity has been detected already at 10 bars. For glucose oxidase the intensification factor for enzyme activity was up to 2.5, and amino acid oxidase showed an intensification factor up to 6 for the enzyme activity. High product concentration, with the concentration being 6 to 10 times higher at 34 bars compared to atmospheric pressure has been demonstrated. Reactions of glucose oxidase and amino acid oxidase were used both as soluble enzyme in liquid flow and immobilized enzyme in a packed bed as exemplary cases to demonstrate that the pressurized continuous flow reactor presents a powerful engineering tool uniquely apt to overcome restrictions inherent to the individual O2-dependent transformation consideredThe base for the performance push when using up to 34 bars of pressure is a 34 – 170 fold increase of dissolved oxygen compared to oxygen dissolved at atmospheric pressure.  

published on May 11, 2020




Modular plants enable API production in Europe

Export bans of Active Pharmaceutical Ingredients (APIs) and intermediates by India and China, caused by the global COVID-19 crisis, have led many companies to consider bringing back their production to Europe. This can only be done with a cost-efficient technology approach. Universal engineering designs and intesified processes are a good base for this. Companies like Microinnova have 15 years of experience to apply in rapidly developing chemical processes for demanding reactions.

This competence of Microinnova enables a quicker response to a spontaneous demand of a specific molecule. As seen in the past, a considerable demand for specific APIs or intermediates can arise with short notice. The minimizing of development and production times are critical, especially in the case of the outbreak of a new disease. A new production process can be employed rapidly through already constructed or even pre-existing modules which are applied in new combinations. This aids in APIs and medical treatment being available sooner.

Microinnova has already technically specified and built multiple modular plants for various pharma companies. Aside from fast realization, economic advantages further facilitate the possibility to bringing back production of some intermediates and APIs from Asia to Europe. Based on a high level of research activities in the past, Microinnova is proud to offer effective solutions to many customers now.

published on May 7, 2020


Microinnova is proud to be a 3 Star Sponsor of the Flow Chemistry Conference by Scientific Update

We are proud to announce our 3 Star sponsorship of this online Flow Chemistry Conference, hosted by Scientific Update, taking place May 11 & 12, 2020. The focus of this conference will be on case studies from process chemists and engineers who will be sharing their insights, examples and opinions.

As an expert in flow chemistry, continuous mixing plants and continuous manufacturing, Microinnova is especially excited for this event to further enlighten more of the industry to the vast advantages flow chemistry offers. Our commitment to help producers make the switch from batch to continuous processing leads to a number of economic benefits that in turn help our customers become more profitable. We are proud to be able to offer you our one-stop-shop solutions. Not only will we do process design and feasibility studies, but we also optimize pilot plants and even build entire plants for you, which according to the requirements can feature CE, ATEX or GMP compliance.

Sign up here »

published on May 6, 2020


Environmental & economic impact of solvent-free continuous API manufacturing of Rufinamide

In the pharma and fine chemical industries, the development of continuous flow technologies is a process intensification step of primary importance towards the manufacturing of high‐quality products, while reducing the environmental impact and cost of production. The sustainability and profitability of a process can be measured through life cycle assessment and cost evaluation. However, when applied to emerging technologies based on flow chemistry, these need to be performed at different stages of the process development in order to limit the uncertainties arising from the scale‐up, and hence providing high‐fidelity projections of environmental impacts and costs at larger scales.

Therefore, in this article, we perform an assessment at two different scales of production, lab and mini pilot plant scale, with the aim of quantifying the uncertainties of the assessment related to the scale‐up, identifying the hotspots of the system, and hence providing guidelines for the further steps of process development. The subject of the assessment is the solvent-free continuous flow synthesis of Rufinamide. It is the first time that this synthesis is evaluated at pilot plant scale.

Grimaldi, F., de Leon Izeppi, G. A., Kirschneck, D., Lettieri, P., Escribà-Gelonch, M., & Hessel, V. (2020, February 27). Life cycle assessment and cost evaluation of emerging technologies at early stages: The case of continuous flow synthesis of Rufinamide. Journal of Advanced Manufacturing and Processing.

Find it here »

published on April 22, 2020

 

Microinnova is operating in a new way! Take a look: 

In light of nationwide restrictions in order to influence the impact of COVID-19, most of the Microinnova Team has transitioned to work remotely. The lab remains in operation according to current laws and regulations. Tasks demanding lab time are scheduled in such a way that our lab workers are able to minimize social contact, as well as keep up with the projects they are working on. 

Due to the effects of this outbreak there is a need for a reorganization of projects. We are working tirelessly to ensure that we fulfill the needs of our customers. Our flexibility ensures a response to varying project demands. 

We do our best to serve our customers the usual way. We are happy to discuss new projects as well. We see these unusual times as an excellent opportunity to discuss and develop future strategies. Take this chance to contact us!

published on March 19, 2020

 

Forging Flow Chemistry Bond

Microinnova Engineering GmbH and Research Center Pharmaceutical Engineering GmbH (RCPE) are entering into a very promising collaboration. Microinnova is specialized in continuous modular plant design and flow process scale-up, as well as realizing continuous pilot and manufacturing scale plants. RCPE is a global leader in pharmaceutical engineering sciences and with its CCFLOW Area (Center for Continuous Flow Synthesis and Processing) it offers, amongst others, core competences in flow chemistry, process development, control strategy and online analytics (PAT), taking the lead in developing chemical routes, chemical simulations and determining reaction kinetics.

Their cooperation intends to synergize the competences for continuous manufacturing of chemicals and APIs of both involved teams, using various methods of process intensification, leading to a competence hub for these innovative technologies in the Graz area. Johannes Khinast and Thomas Klein (CEOs of RCPE), C. Oliver Kappe (Scientific Director of CCFLOW) and Dirk Kirschneck (Strategic Director of Microinnova Engineering GmbH) see the region as an important hub of continuous manufacturing for the pharmaceutical industry.

published on February 10, 2020

 

 

Release of the VDI 2776 Guideline


Sheet number 1 regarding the topic "Process engineering plants - Modular plants - Planning modular plants" has been released. Access it here

published on February 26, 2020

 

 
 

 

 

 

 

CPhI Pharma Awards 2019

We are very honored and pleased to announce that we have been nominated for the CPhI Pharma Awards 2019

published on November 5, 2019

 

Research via the COSMIC project

Microinnova is one of the beneficiaries of COSMIC, a Marie Skłodowska-Curie Action for Innovative training Network (EU Horizon 2020 Grant Agreement No 721290). COSMIC, the European Training Network for Continuous Sonication and Microwave Reactors, is a key instrument for supporting and training the chemical process industry in their transition from batch to continuous production. The project involves 15 early stage researchers spread in different European universities and companies. A key factor of the project is the exchange of know-how and the development of new technologies in synergism between all the participants. Currently, Alessio Zuliani, from the University of Córdoba (ES), is accomplishing a secondment at Microinnova, working on the synthesis of silver nanoparticles.

published on February 13, 2019

 

Secondments - Mobility and training in Leuven as part of the COSMIC project

How to compare conventional technologies versus non-conventional on industrial scale? Which approaches considering CAPEX and OPEX lead to a solid decision basis for technology investments? These questions were actively investigated by Gerardo de Leon Izeppi in the scope of the ETN project COSMIC (Continuous Sonication and Microwave Reactors) during his secondment at KU Leuven. Microinnova is the main project partner enhancing knowledge-based assessments and decision methodologies to evaluate and select PI technologies for industrial production processes.

published on July 26, 2018

 

PICASSO pilot-scale tests performed at Microinnova

Microinnova is the main partner in the ERC-funded project "Piloting cascaded continuous flow synthesis for the pharmaceutical industry" (PICASCO) run by TU Eindhoven. This project aims to deliver the commercial proof of concept of a novel end-to-end flow manufacturing and a novel corresponding compact flow mini plant. The goal is achieved through the first continuous 4-step solvent-free flow manufacturing of a pharmaceutically relevant API compound at an industrial scale. The project is currently in the pilot-scale tests, which are performed at Microinnova in Graz (Austria).

published on April 11, 2018

 

Microinnova passes ISO 9001:2015 audit

Microinnova Engineering is pleased to announce that it has passed the certification audit for DIN EN ISO 9001:2015. This achievement recognizes Microinnova's ongoing commitment to remain compliant to a world leading quality standard whilst also highlighting the business’s enthusiasm for delivering excellent products and services in the chemical and pharmaceutical industry. This standard is based on a number of quality management principles including a strong customer focus, the motivation and implication of top management, the process approach and continual improvement. By mapping our ISO 9001 process exactly to how we execute work, we maintain an efficient system that is fully embraced by our employees. We demonstrate our commitment to our overarching corporate goal: meeting high customer expectations.

published on March 7, 2018

 

Successful commissioning of the continuous crystallization filtering and drying pilot plant for the Shefflied University

At the beginning of October our Project Manager Walter Linhart visited our customer the Sheffield University in the UK. After the successfully completed factory acceptance test we put it successful into operation.

 

Synthetic biofuel from sustainable sources

 

Evonik Nutrition & Care GmbH orders an API plant

 

Scale up of a solvent-free multi-step API Synthesis in continuous-flow

Microinnova has been selected as industrial partner for the Project PICASCO. Prof. Dr. V. Hessel from TU Eindhoven won an ERC Proof of Concept Grant. The aim of PICASCO is the commercial proof of concept for a novel compact flow miniplant based on end-to-end manufacturing of multiple reaction steps in continuous-flow. This flow manufacturing approach enables a high specific productivity in solvent-free processing. We congratulate Prof. Dr. V. Hessel on his success and ambitious visions for industrial realization. 

published on August 10, 2017 

 

We developed a continuous crystallization plant for the Sheffield University

As a specialist in innovative process technology Microinnova Engineering develops customer-specific solutions. We have built a continuous crystallization plant for our customer, the Sheffield University. The University of Sheffield was founded in 1905 and is one of the world's most prestigious universities with approximately 25,500 students and 1200 scientific staff and has particularly good rankings especially in the Department of Chemistry. Quality and customer satisfaction are very important for us. We are proud to announce that we have successfully executed a continuous crystallisation plant factory acceptance test to the full satisfaction of our customer.

published on July 11, 2017 

 

Microinnova at the Chemspec Europe 2017

Last week, our CEO, Dr. Kirschneck, gave an exciting presentation about continuous processes in the Chemspec Europe. Important aspects were the petrochemical industry and its transition to the continuous processing.The focus today is a complex application that allows the reduction of mass and heat transfer distances. The downstream processing, as well as the formulation manufacture opens up a broad spectrum of new fields of continuous production. Economic strategies and three case studies were also pointed out. The first demonstrates the propoxylation reaction, the second an API production plant and the third a pilot plant for crystallization processes.

published on June 6, 2017 

 

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