It takes a great deal of time and money to develop a new drug. At Biotechnica in Hanover from October 9 to 11, the Fraunhofer Life Sciences Alliance will demonstrate how a pharmaceutical agent can make its way more quickly from the research laboratory to the pharmacy.
Developing new medicines is a tedious, time-consuming and expensive business. It takes about 12 years for a new drug to reach the patient. On average, only one in 10,000 tested substances receives approval as a medicine. Many projects are discontinued after years of development because the products are not sufficiently potent or have unacceptable side-effects. As a result, the cost of developing a drug can quickly rise to between 500 and 800 million euros. “It’s much more difficult and expensive to put a drug on the market today than it was ten years ago,” says Dr. Uwe Heinrich, chairman of the Fraunhofer Life Sciences Alliance. Fraunhofer researchers are helping the industry to speed up the entire drug development process – from identifying target structures and active agents to conducting Phase I and II clinical studies, testing substances for side-effects along the way.
The first step in developing a new medicine is to find a point of attack in the pathological process where a drug could be applied. These target structures are usually enzymes, receptors and other proteins. Geneticists and molecular biologists have identified thousands of disease-related genes and proteins. But which of these countless target molecules could be a suitable candidate for developing a drug? To answer this question, the interaction of a potential target with other genes and proteins must be thoroughly investigated. Only then is it justifiable to invest large sums in drug development and approval.
Researchers at the Fraunhofer Institute for Biomedical Technology IBMT have developed a cell-based in-vitro test platform for target validation. “We can even subject three-dimensional tissue models to several weeks of non-destructive testing, and investigate potential therapies,” explains Dr. Hagen Thielecke of the IBMT. The researchers have set up test systems for myocardial cells, smooth muscle cells and vascular endothelial cells. These will allow them to research possible starting points for the treatment of cardiovascular diseases. The system is currently also being used to characterize different types of stem cells in terms of their ability to form bone cells, and to test different gene therapy approaches.
The next step is to find suitable agents. The scientists start off with more than 10,000 substances. Using automatic test systems, they filter out candidates that exhibit an effect on certain pathological processes. Researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB use cell-based assays to identify agents that block validated targets. “This is done by bringing several tens of thousands of substances in contact with a target-specific reporter assay in the presence of human cell cultures,” explains Dr. Steffen Rupp. To test whether or not a substance has an effect, a fluorescent protein is selectively switched on or off, depending on the test set-up. The human cells employed in the process enable the researchers to simultaneously test whether or not the agent has a cytotoxic effect in general. This eventually leaves the researchers with about 100 substances. In order to rapidly determine suitable agents for drug development from among these candidates, they need to be able to assess the effect and toxicity of a new substance at an early stage. Researchers at the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM use gene and protein expression analysis for this purpose. This enables them to test the effect of a substance on gene activity and subsequently to draw conclusions as to possible side-effects. First of all, the gene expression profiles of the potential agents are compared with those of substances whose harmful effects are already known. If a newly researched agent displays a similar signature to that of a drug that causes liver damage, for example, then this substance is likely to have the same side-effect. As for toxic properties, the most important indicators are provided by tests on cell and organ structures. But how will the new agent be absorbed, distributed and metabolized by the body? Will toxic degradation products emerge in the process, potentially leading to undesired side-effects? Tests on three-dimensional tissue systems developed by scientists at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB can provide the answers. These scientists have succeeded in producing human tissue belonging to different organs such as the skin, liver and intestines. The special feature of this ‘artificial’ tissue is that it actually has blood vessels to supply it. This allows conclusive tests to be carried out on the effects of different drugs. These tests complement the results of animal experiments, which show how the substances work in a complex organism and in what doses they start to become toxic.
Once a promising agent has been found, it has to be produced in small quantities for clinical tests according to Good Manufacturing Practice (GMP) guidelines. The Fraunhofer Institutes for Molecular Biology and Applied Ecology IME and for Cell Therapy and Immunology IZI are able to produce therapeutic, recombinant proteins under GMP conditions. The IZI also has the capacity for GMP-compliant manufacture of cell therapeutics and test systems. New technologies have been established to investigate therapeutics for treating cancer and other diseases. This model system makes it possible to systematically test how new types of agent are distributed inside the organism. The IGB can produce cell systems for organ replacement according to GMP guidelines.
Before a new drug is approved for the treatment of patients, it has to undergo clinical studies to demonstrate its effectiveness and safety. The ITEM carries out clinical studies according to internationally standardized Good Clinical Practice (GCP) guidelines in collaboration with the Hanover Medical School (MHH). The ITEM researchers specialize in clinical studies for the approval of drugs to treat respiratory diseases such as asthma, chronic bronchitis and hay fever. Agents are only approved for medical use once they have passed these clinical tests.
The route from a chemical molecule to a prescription drug is long and arduous. New research findings and technologies are helping to make it safer and shorter. The topic of ‘accelerated drug development’ will be presented by Fraunhofer researchers in Hall 9, Stand E29. We offer journalists individual guided tours of the Fraunhofer stand.