GLP Test Facility

As part of a collaborative project, funded by the German Federal Ministry of Education and Research, a safety study is being conducted to evaluate the toxicity and safety of a small-molecule active ingredient for the treatment of periodontitis. The active ingredient specifically inhibits enzymes of oral germs that are largely responsible for the development of periodontitis and associated secondary diseases. Due to the selective effect, the natural microbiome remains largely unaffected, which can be seen as an advantage over conventional antibiotic-based therapies. The GLP study will create the essential prerequisites for the envisaged clinical trial.

With the ROR2-CAR-T cell therapy, scientists at the University Hospital of Würzburg have developed an immunotherapy that differs from previously approved therapies both in the type of genetic modification and the target antigen addressed. This is now to be transferred to clinical application as part of a project funded by the German Federal Ministry of Education and Research. The GLP-compliant testing for safety and efficacy is an essential prerequisite for the application and implementation of the intended clinical study.

Preclinical trials are underway to investigate a combination painkiller as part of a joint project funded by the German Federal Ministry of Education and Research. The project aims to minimize safety risks before the drug is used for the first time in patients. The preparation combines an opiate with a dendritic nanotransport molecule (nanocarrier). Preclinical investigations are being carried out under GLP conditions into the safety of the drug using appropriate animal models (small animal model, large animal model) at Fraunhofer IZI. Together with the investigational drug’s manufacture under GMP conditions by the company DendroPharm, the prerequisites are met for the developed drug to then be investigated in a phase I clinical trial at the Fraunhofer Institute for Toxicology and Experimental Medicine. The safety and tolerability of the drug will also be tested on healthy human subjects in single and multiple ascending doses. This marks a further step towards the market maturity of a potential, new pain medication.

In two pre-clinical study arms, the systemic toxicity of the therapeutic vaccines, on the one hand, and the immuno-toxicity, on the other, are assessed in the relevant disease model in mice. This is to be used to examine potential toxic side-effects of the individual vaccine components (HBV peptides, adjuvants, MVA vector) in the event of a repeated maximum dose under an established vaccination schedule, with the help of histopathological, haematological and clinical-chemical analyses. The relevant murine disease model (which imitates chronic hepatitis) is aimed at evaluating immunotoxic effects, on the one hand, and to confirm the effectiveness of the vaccines, on the other.

Since this novel product is a medical product of risk class III, preclinical and clinical examinations have to be carried out under the German medical products law in order to ensure its biological safety.

These safety checks were carried out at the GKP testing facility of the Fraunhofer IZI based on DIN EN ISO 10993. During these examinations, reduction studies were carried out in order to characterise the individual degradation products of the resorbable implant. Furthermore, according to DIN EN ISO 10993-5, the cytotoxic potential of the framework structure was examined in vitro. Systemic toxicity and the local effects after implantation were evaluated in the mouse, using histopathological, haematological and clinical-chemical analyses. In addition to safety, the implantation strategy is also established in Göttingen minipigs under GLP-analogue conditions in order to guarantee the functionality and, ultimately, a low-complication rate application in patients.

• Preclinical safety testing to evaluate biodistribution and tumorigenicity in matrix-associated autologous chondrocyte transplantation (MACT) based on human mesenchymal stem cells in the NSG mouse model
• Toxicological investigation of an active substance for the treatment of multi-resistant bacterial strains
• Toxicological investigation of an active substance for the treatment of psoriasis
• Differential protein biochemical and serological investigation of UVC-irradiated and non-irradiated canine platelet concentrates
• Immunotoxicological in vitro testing of the herbal immunostimulant mistletoe extract on intestinal epithelial cells
• Safety and efficacy testing of MSC-generated cartilage preparations after autologous implantation in a large animal model (sheep)
• Safety and efficacy testing of autologous chondrocyte spheroids after implantation in a large animal model (sheep)
• Preclinical safety testing to evaluate the biodistribution and tumorigenicity of tissue-engineered human chondrocyte spheroids in an NSG mouse model (followed by clinical testing: NCT01225575, NCT01222559)
• Safety and efficacy testing of a novel breast implant manufactured using 3D printing (followed by clinical trial: NCT05437757)
• Preclinical safety testing to assess the immunotoxicity of a therapeutic HBV vaccine – TherVacB (followed by clinical trial: NCT06513286)
• Preclinical safety testing of an allogeneic, matrix-associated cell transplant from mesenchymal stromal cells of umbilical cord tissue (followed by clinical trial: NCT06981741)
• Preclinical GLP study for safety testing of a CAR-T cell therapy targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1) in an NSG mouse model (followed by clinical trial: LION-1)
• Immunohistochemical detection of ROR2 in a tissue cross-reactivity study with the ROR2-specific scFv