Microfluidic Advanced Manufacturing of Ultrasound Contrast Agents

Project Information

MAMANUCA

Grant agreement ID: 663065

DOI

10.3030/663065

Project closed

EC signature date 21 January 2015

Start date 1 February 2015

End date 31 July 2015

Funded under

• INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Nanotechnologies

Total cost

€ 71 429,00

EU contribution

€ 50 000,00

Coordinated by

TIDE MICROFLUIDICS BV
Netherlands

Periodic Reporting for period 1 - MAMANUCA (Microfluidic Advanced Manufacturing of Ultrasound Contrast Agents)

Reporting period: 2015-02-01 to 2015-07-31

Summary of the context and overall objectives of the project

Tide Microfluidics develops proprietary microfluidic technology for improved diagnostic capability of contrast enhanced ultrasound imaging. We have an advanced microfluidic manufacturing technique for producing ultrasound contrast agents (UCA) of controlled size to enable 20 times clearer images. Our uniform UCAs are unique, as current UCAs are composed of wide size distribution microbubbles, making them less effective. We aim to develop our technology into a bedside UCA production device, which would lead to a reduction in diagnostic imaging costs, as ultrasound is cheaper than MRI or CT, and gives better images for faster and more accurate diagnoses. During MAManUCA, our SME-Instrument phase 1 we have assessed the commercially and technically feasibility of our bedside UCA production device concept. Our aim was to understand the users requirements and how best to fit into their workflow, as well as how to create a robust, reliable and user-friendly design. Economic viability was studied, as pricing must be cost effective or market uptake will not occur. Finally, we have investigated the clinical validation needs and level of medical certification required for our bedside production device to be accepted in Europe, the USA and the rest of the world. This knowledge on feasibility, cost pricing and validation defined in Phase 1 will work as a roadmap for our development during a Phase 2 project. Thus, exploitation of SME-Instrument Phases 1 and 2 would secure the continuous development and validation of our device allowing for a rapid market entry, bringing a valuable tool to the end users and reducing healthcare costs. We aim to enter the ultrasound imaging market with our bedside UCA production device. Currently, more than 3 million ultrasound procedures using UCA‘s are carried out each year worldwide, with the European market alone worth $46 million. Ultimately, our vision is to become the world’s foremost supplier of UCA production devices delivering high definition contrast agents, enabling clearer diagnostic images for more effective patient care.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Our work has focussed on addressing the EU objective for improving health, demographic change and well-being. We have investigated the use of our company’s microfluidic technology for enabling advanced manufacturing of much needed pharmaceutical products for both diagnostic and therapeutic ultrasound procedures. By studying the feasibility of our preclinical prototype for different areas of application we have determined the optimal route to further develop our technology for clinical use. We have investigated four key areas of feasibility, which are crucial for our development, these are:

Supply chain study - We investigated how the supply chains for current UCAs are constructed in order to identify how our technology can be smoothly introduced using a similar supply and distribution network.
Our results showed current products are distributed through direct sales, with hospitals using a secure webshop to purchase stocks of UCAs. Our survey results mean we will focus on developing our customer network based on direct sales and developing one-to-one relationships with key opinion makers to act as both launching customers and advocates for our product. We believe through their testimonials of the value for our product we will be able to reach a wider audience and bring our product successfully to the market.

Clinical validation - We evaluated which diagnostic area we will carry out or initial clinical validation for and how to proceed with this validation.
As a result of our study we were able to shortlist three key areas where we see great potential in entering the market with our product clinically validated. We focus initially on the diagnostics market as this is a well-developed market; however we see opportunities for the future within the therapeutics market once this sector and our company are both more established. The diagnostic ultrasound sector is very wide and we have selected and initial entry focussed on a selected diagnostic application with back-up applications in place for our route to clinical validation, should our initial path be compromised.
Further, we have mapped the path to a clinically validated bedside production device during our MAManUCA project. Our study has shown that we will need to complete our preclinical testing to define the safe working dose of UCAs created using our bedside production device, as well as creating a working protocol for the use of our bedside production device and the produced UCA that are compatible with the clinical environment. Once this protocol has been discussed with the European medicines agency (EMA), we will proceed to our clinical trials stage.

Usability survey - A successful introduction of our innovative technology requires full understanding of the current working process of the end-user and how to improve it. The usability survey includes understanding current user protocols and defining functional and technical user requirements for our bedside microfluidic platform based on current working.
We surveyed medical professionals in a range of clinical settings including, key opinion makers, leading research clinicians and the more general population of ultrasound users at non-teaching and research hospitals. We believe in looking at both the standard hospital practices as well as the cutting-edge medical research hospitals will ensure that our product fits into the clinical workflow of any ultrasound procedure. To further understand the needs of UCA users we are using our newly launched MicroSphere Creator as an introductory tool. The feedback we have received from leading clinicians and researchers, using this system, has fed directly in to the development steps we are taking with our bedside apparatus.

Certification - Mapping the route to certification and how it will be validated has been a key activity of the work proposed in this project.
Through discussions with regulatory bodies and certification advisors, as well as through our own investigations we have defined the key steps towards the certification level we will need for our bedside microfluidic platform and the best route to obtaining this certification. Our findings have shown that our bedside production device can be considered as a pharmaceutical product, which means to achieve certification we will be assessed and guide by the European medicines agency (EMA), who we are currently in discussions with over our development path.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our results from all aspects of our feasibility have shown that our envisaged bedside UCA production device is both economically viable and able to meet an import diagnostic healthcare need. We plan to take our findings from MAManUCA and use these as a basis for both our company and our product development. This will include the submission of a proposal to SME-Instrument Phase 2, within which we hope to continue our product development towards the initiation of clinical trials under the guidance of the EMA. We believe that a bedside production device for the generation of UCAs at the point of need can support more cost efficient medical diagnostics that provide high quality imaging results whilst being non-invasive and more patient-friendly. In general we see the increased use of contrast enhanced ultrasound diagnostics as being a key tool in enabling a more sustainable healthcare system for Europe and the world as a whole.

Mobile apparatus for the production of uniform ultrasound contrast agents