High-Performance Center Translational Biomedical Engineering – an interview with Prof. Theodor Doll

A Fraunhofer ITEM lighthouse project

Medical devices can significantly improve patients’ quality of life. To this end, numerous universities and research laboratories are constantly developing new and innovative solutions, which then have to go through a long and often arduous registration process. Aimed at bringing medical devices from the lab into clinical trials and at overcoming scientific and economic hurdles of the development process, the High-Performance Center Translational Biomedical Engineering was established in 2017. It is one of the lighthouse projects of Fraunhofer ITEM.

Prof. Theodor Doll explains what exactly the High-Performance Center is and the added value that comes from its activities. He is head of the High-Performance Center and holds a concurrent professorship instituted together by the Hannover Medical School and Fraunhofer ITEM.

Professor Doll, what is a High-Performance Center?

With its High-Performance Centers, the Fraunhofer-Gesellschaft as an organization of applied research supports innovation processes at the regional level. High-Performance Centers organize a strategic topic-based collaboration between several public and private research and development partners. Universities, higher education institutions, Fraunhofer Institutes and other non-university research institutions at a particular location work together with companies and civil society players in a defined subject area and on an application-oriented basis to quickly translate innovations into clinical applications. High-Performance Centers stand for excellent infrastructure that is used in a cross-organizational manner, education concepts, and expertise. They bring together appropriate partners and, as innovation guides, advance ideas to market launch. This concept of collaboration in translation-oriented High-Performance Centers has already been put into practice at 17 locations in 11 German federal states.

With the High-Performance Center Translational Biomedical Engineering the Fraunhofer-Gesellschaft as an organization at the interface of academia and industry is supporting innovation processes in the biomedical engineering sector in the Hannover area and thus at the location of the Fraunhofer Institute in Hannover. The Center also receives funding from the regional government of Lower Saxony. Together with our partners, we can provide decisive impetus for future innovations to industry, SMEs and start-ups in the medical sector.

Prof. Theodor Doll explains what exactly the High-Performance Center is.
© Fraunhofer ITEM, Till Holland
Prof. Theodor Doll explains what exactly the High-Performance Center is and the added value that comes from its activities.

Who are the partners in the High-Performance Center Translational Biomedical Engineering?

Fraunhofer ITEM and the Lower Saxony Center for Biomedical Engineering, Implant Research and Development, NIFE for short, are collaborating in the High-Performance Center and also in the Cluster of Excellence Hearing4all.

How does the High-Performance Center support academia and industry?

Our commitment is to close the gap between basic research and the first clinical trial – regarding regulatory support, quality assurance, and manufacturing technology. We place particular emphasis on safety aspects – after all, biomedical engineering products are made for people, for patients. In cooperation with partner institutions we cover the whole chain from innovation to a CE-compliant product.

We equip companies and entrepreneurs with the technical and regulatory support that will allow their innovations to enter and pass clinical testing. This also includes dedicated manufacturing processes that usually represent substantial economic hurdles for companies. These processes can be provided by our partners and are pooled within the High-Performance Center with corresponding quality and risk management structures for medical devices, supplemented by appropriate process logistics to provide a one-stop shop. In addition, we guide clients along the regulatory pathway including the necessary documentation, arrange or conduct the required tests and optimize these according to the requirements of the innovation in close contact with the notified body.

Speaking of registration: How do you think will the new EU-wide Medical Device Regulation affect the biomedical engineering sector?

First and foremost, patient safety is top priority in medicine and biomedical engineering. It is thus a good thing that an EU-wide uniform regulation, the Medical Device Regulation, or MDR for short, was introduced in 2017. Nonetheless, the MDR poses enormous challenges for the biomedical engineering sector. To ensure compliance with the new legislation, manufacturers have to meet increased documentation and testing requirements, also for products that are already on the market. Furthermore, many questions concerning the practical implementation of the regulation are still unanswered. Small and medium-sized enterprises in particular fear that meeting the requirements will be too much for them, also financially, which would reduce the innovative strength of the biomedical engineering sector in Germany in the long term.

Are there figures supporting your concern?

To obtain as complete a picture as possible of the consequences to be expected from the MDR, Fraunhofer ITEM together with the MDR Competence network and Deloitte GmbH performed a market survey that yielded alarming results. Only 15 percent of manufacturers feel sufficiently informed about implementation of the MDR. Fifty percent of the respondents reckon that products or product lines will have to be terminated because of the increased requirements. Over 65 percent of companies feel compelled to shift resources from development to regulatory issues – at the expense of innovation efforts. And 70 percent of companies are feeling uncertain as to whether the notified bodies that have assisted them so far will continue to do so to allow all deadlines to be met.

The consequences for the biomedical engineering sector in Germany and Europe are huge, the more so because small and medium-sized enterprises, SMEs for short, are considered the major innovation drivers in this sector, accounting for 93 percent of all medtech companies. These, however, are particularly affected by the negative effects of the MDR, facing challenges that they can hardly manage. Development costs and time will substantially increase, leading to markedly deteriorating prospects of start-ups and SMEs in this sector. Likewise, it will become much less attractive for investors to invest in innovative medtech developments. The figures give reason to fear that in the medium term the regulation will result in migration towards the FDA-regulated American market and depletion of the innovation hotspot Germany.

How can the High-Performance Center provide support in the implementation of the MDR?

In September 2018, our High-Performance Center invited stakeholders from industry and professional associations in the biomedical engineering sector to a discussion forum dealing with the question “How to survive with the European MDR?”  Experts exchanged information regarding the current state of MDR implementation and discussed its impact. Together with the participants of this event, we defined specific measures that could both relieve the current situation and restore confidence in the innovation hotspot Germany for the future. These measures include accelerated accreditation of notified bodies , correction of deadlines for manufacturers, development of implementation guides, introduction of special regulations for conformity assessment, and avoidance of trust-like structures.

With our professional expertise pooled in the High-Performance Center, we offer advanced professional training for executives and junior staff in biomedical engineering companies, especially on regulatory issues.

Precisely speaking, at Fraunhofer ITEM in particular we support clients in their MDR-compliant development of innovative medical devices or in making adjustments to existing products to achieve compliance with the new regulations. In a one-stop shop, we devise a risk management strategy according to the ISO 14971 standard, perform biological evaluation of the medical device as part of the risk management process, and offer relevant in-vitro and in-vivo tests from the ISO 10993 series of standards. Clinical assessment is performed primarily based on scientific literature and, if required, can be complemented by clinical testing. We can provide optimal support to medical device manufacturers, as we pool our expertise in medical devices with our long-term experience in chemical risk assessment, nanomaterials, and biocompatibility.

Within the High-Performance Center, Fraunhofer ITEM also engages in the development and manufacturing of biomedical engineering products. What is your focus?

One focus in our team is on neural implants. Personalized medicine or rather personalized biomedical engineering is aimed at producing individualized prostheses and implants for each patient. This is where the development of a 3D printing process for medical-grade silicones is coming into play. In the High-Performance Center, we are further developing a 3D printing technology developed by the Hannover Medical School, to make it suitable for industrial use – and not only that: We are enhancing it into a manufacturing chain with integrated sensors, actuators and electronics. With this approach, the High-Performance Center is in a top position worldwide.

As a partner in the Cluster of Excellence Hearing4all, we are proud that this cluster has been selected for funding for the second time. Hearing4all is one of the world's leading centers in medical technology, hearing research, audiology, medical diagnostics, and therapy. Every cochlear implant in use around the world is somehow based on research conducted in Hannover and, to a certain extent, also on research by Fraunhofer ITEM.

The focus at Fraunhofer ITEM is on airway research – is this focus also reflected in the development of medical devices at Fraunhofer ITEM?

Inhaled aerosol therapies are getting more and more important in the medical area. At Fraunhofer ITEM, we are developing technologies for the administration of medical aerosols. An example is the development of an inhalation system for preterm infants whose lungs are not yet fully developed. They need a substance called surfactant, which allows the alveoli to expand with inspiration. It is not sufficient in this case to administer surfactant in the form of nebulized droplets, it has to be administered as dry powder via the breathing air. To avoid particle deposition in the upper airways, the dry substance needs to be humidified. Exact timing of this humidification is crucial, namely during inspiration. If you consider that the tidal volume of a preterm infant is less than half a shotglass, you can see the special challenge we are facing. The new technology will shorten therapy duration, thereby easing the strain on these little infants.

The way the system is currently designed, it can basically be used for inhaled drug administration to preterm infants, children, and also to adults. A first clinical prototype is available for use in clinical trials with adults. I guess it will take another three to five years before the system is ready for serial production.

We see great potential in this technology, because the system allows drugs to be delivered very specifically and efficiently to certain areas of the lung and exactly during the period of inhalation.

Our developments can give patients a better quality of life and improve their health.