"It takes a long time to get a medical drug ready for the market and clinical application. Only ten percent of all new drugs make it from initial development in the lab to clinical use. One particularly critical phase, known as preclinical development, comes when new drugs undergo extensive trials and testing. The uppermost priority of this stringent approval process is to guarantee the safety of patients prior to first use of the product. It is at this transition from basic scientific research to further medical development where drug candidates that initially seem promising often fail – though in many cases the failure only comes at a very late stage. Often it only becomes clear at the very end of the preclinical trial phase that drugs are not effective or entail side effects. We scientists talk in this context about the 'Valley of Death'. At the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in Hanover, we want to help bridge this critical phase.
Early screening, lower costs
With this goal in mind, I work in the department of inhalable drugs and helped develop the 'InhalDrug Test'. Chronic lung diseases and asthma are a widespread problem worldwide. The lung is not only an important target organ for acute toxic effects; its barrier function also determines the uptake of airborne substances into the blood and lymphatic system – which has consequences for all other organs. An important objective is, therefore, to develop new ways of preventing, diagnosing and treating diseases as quickly and effectively as possible.
If we want to speed up the development of drugs, we need meaningful in-vitro models. This is the only way to assess the efficacy of substances and check for any side effects at an early point in the lengthy product development process, and if necessary to reject them. This saves a lot of time and money. In cooperation with the Berlin-based biotech company TissUse GmbH, the Fraunhofer Institute is developing a device-based procedure for inhalable drugs. This process will allow early screening of airborne substances such as those used in nasal sprays and inhalers.
Humans on a chip
One of the big challenges was to observe the effect of inhalable substances such as particles, gases or droplets under realistic conditions, that is to say on their path into the lungs. The 'Human-on-a-Chip' systems developed by TissUse give us preclinical insights on the system biology level. The chips are the size of the glass slides used for microscopy; most of us will be familiar with them from our schooldays. The small devices comprise several separate cell compartments into which cell cultures and tissue sections from organs such as the heart, lung or liver can be inserted. Just like in the human body, different organ models can be simulated in an interconnected circuit on a single chip. These microstructures are connected to one another by small channels through which nutrient media or substances dissolved in plasma can circulate. This allows scientists to study not only the way the cells interact with the introduced substances, but also resulting effects on other organs. Side effects can be identified at an early stage using this method.
This process has obvious benefits for the pharmaceuticals industry. Companies save money because they avoid unnecessary further development steps and can get substances to the clinical development stage earlier. We have an even higher goal, however: we hope that our project will help replace in-vivo animal experiments with new methodological approaches or will at least reduce their number. Animal experiments are still standard practice when it comes to assessing the risks of pharmaceuticals. However, what we want to be able to predict in pharmaceutical research is how a new substance will affect humans. With our 'InhalDrug Test' we are offering a method that makes sound scientific sense and improves patient safety because we work exclusively with human cell cultures. When animal samples are used, the results from the cell culture cannot always be applied unequivocally to the human organism.
Test system serves as a model
Within the framework of the collaborative project NanoINHAL, which is being funded for three years by Germany’s Federal Ministry of Education and Research (BMBF), we are currently beginning to put our project into practice. As well as promoting computer-based models and making better use of existing data, our method serves as a step towards accelerating pharmaceutical development processes."
Dr Tanja Hansen
Dr Hansen has a PhD in veterinary medicine and heads the Working Group on In-vitro Test Systems at the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in Hanover (Germany). Dr Hansen was a participant at InnoHealth Australia (2018-2019). Together with Dr Katharina Schimek from TissUse GmbH, she was a member of one of the German SME tandems at InnoHealth Australia. During the InnoHealth event, she had the opportunity to present her project in Australia and intensify her cooperation with her business partner. The programme is now being continued with a new country focus on China: InnoHealth China.www.item.fraunhofer.de > Mechanistic and in-vitro toxicology
As part of the Research in Germany initiative, InnoHealth China is the current campaign for the period 2019-2020 led by the Fraunhofer-Gesellschaft. The campaign aims to connect the German and Chinese health research sectors, also involving SMEs and start-ups. Participants are given the chance to learn more about each other in terms of research, business approach and culture. These insights into high-tech competencies and research excellence should lead to new cooperation ideas and concrete partnerships. For more information about participating in InnoHealth China, visitwww.research-in-germany.org > Call for Ideas & Innovation