Taking biopharmaceutical substances that are contaminated with proteins for example, might lead to severe side effects of an inflammatory or allergic nature. In order to avoid this, comprehensive quality testing is required prior to carrying out clinical studies. And this is where Dr. René Moser and his team of 10 at IBR Inc. come in. Since its foundation in 1998, the GLP testing laboratory, which is based in Matzingen, has been carrying out investigations in bioanalytics, molecular analytics and pharmaceutical analytics. The company also develops new biological and analytical tests and methods, designed to improve existing basic technologies. "In the field of diagnostics and more specifically, clinical studies, we focus mainly on immunology, cell biology and drug monitoring, offering stability and immunotoxicological investigations," said IBR Inc.'s CEO, Dr. René Moser.

In order to guarantee the safety of drugs, IBR Inc. uses, amongst other things, so-called lot release studies for clinical studies. “Many biopharmaceutical substances are applied intravenously. It is therefore extremely important to check these substances for the presence of ‘host cell proteins’. These protein contaminations stem from the cell line that is used for the production of the drug,” explains Dr. René Moser, who habilitated at the Medical Faculty of the University of Zurich in the field of experimental haematology. With the work that it does, IBR Inc. closes an important gap in the market, all the more so because it partners with small biotechnology and pharmaceutical companies. “The particular challenge of such release analysis is that, at this point in the drug development process, we often receive active substances or formulated drugs in limited amounts only,” said the CEO of IBR.

René Moser affirms that small companies in particular find it difficult to carry out both release studies and clinical Phase I and II studies. They usually only have limited quantities of the drug available and they also find it difficult to finance such studies. IBR Inc. develops analyses that enable a company to carry out all the tests that are required for the approval of the substance, based on a minimal amount of substance only. IBR Inc. has developed specific methods that only require minimal amounts of sample and has also adjusted the necessary basic methods and organised the workflow so that only minimal amounts of sample are needed.

“Does the potential drug candidate work as it should and how.” This is the key question that IBR Inc. asks on behalf of small- and medium-sized biotechnology and pharmaceutical companies. René Moser and his team use cellular test systems (bioassays) with which the mechanism of drug action can be simulated under standardised conditions and different batches can subsequently be compared with each other. In addition to biological assays, IBR Inc. also uses ligand-binding assays, which provide information about the binding affinity of therapeutic antibodies or the binding capacity of scavenger molecules. Scavenger molecules are proteins that bind smaller molecules with high affinity and inactivate them. “We know from experience that the combination of biological and chemical analyses gives a comprehensive picture of the effectiveness of a biopharmaceutical substance. The regulatory authorities also increasingly require such a dual strategy,” said René Moser.

The activation of T-lymphocytes (so-called T-cells) in the body is, depending on the point of view, either a sought-after mechanism of action or an undesired side effect. Something that is an important indicator for successful immunisations (vaccine development) might become a safety risk in therapies involving therapeutic antibodies. IBR Inc. uses the ELISPOT method to monitor immune responses. "ELISPOT assays detect cytokines that are released by activated T-cells by way of an enzyme that metabolises a dye. This enzyme is coupled to an antibody and the cytokines detected are visualised as red or blue spots," said René Moser. Each spot represents a specific T-cell and thus enables the scientists to quantify the immune response. T-lymphocytes that are stimulated with a specific antigen produce specific cytokines or cytokine profiles.

T-cells also play a role in investigations relating to cellular mechanisms of proteins or potential active substances that mediate immunosuppression. In the case of substances that are associated with the modulation of the immune system (suppression or activation), the immune status is analysed using numerous different methods. Key factors in such analyses are the proliferation as well as the functional testing of immune system cells. "Phenotyping is either carried out histologically on tissue slices or using isolated cells," said René Moser who was "Oberassistent" (position that corresponds to lecturer level in the UK) at the Institute of Pharmacy at the ETH Zurich in the 1990s. The company uses marker proteins that are specific for the cell population and activation state under investigation. "In the case of immunosuppression, we quantify regulatory T-cells on the basis of the expression of different surface molecules and transcription factors. The actual functional analysis is based on cytokine profiles," added René Moser. Cytokine expression on the RNA level is also assessed on the basis of quantitative RT-PCR.

IBR Inc. uses more than 10 basic technologies from the field of pharmaceutical analytics, immunology and molecular biology. “Each of the analytical methods has its strengths and weaknesses. For us it is important to use the technology and method that are the most appropriate for a certain problem and that lead us to the goal as quickly as possible and with high quality results,” said the IBR Inc. CEO. Molecular biology methods used by Moser and his team increasingly involve quantitative PCR methods, which, according to Moser have “been developed to technical perfection and adapted to routine applications” over the last few years. These methods are reasonably priced and also enable the true quantitative determination of gene expression.

As a result of his long-standing scientific work at the University of Zurich and the ETH, combined with his experience as CEO of IBR, René Moser attaches great importance to the close integration of experimental work (usually molecular basic research), industry and hospitals in the field of biomedicine. In order to promote the cooperation between individual institutions, IBR Inc. and the laboratory technology company Medic Tools established the “Foundation for Biomedical Research” (SBF) in 2001. “We are service providers who work according to strict quality guidelines. Therefore, working with scientists gives us the possibility to directly include findings gained in basic research into our service portfolio. Conversely, the researchers at the foundation benefit from the biopharmaceutical know-how, established technology and efficient approaches of IBR Inc.,” said René Moser.