GLP Test Facility

The department of Therapy Validation enables the design and performance of preclinical efficacy and safety studies for novel drug candidates (especially Advanced Therapy Medicinal Products, ATMPs) and medicinal products (ISO 10993) under GLP or GLP-analogous conditions. This includes the development and validation of suitable in-vitro and in-vivo models. The test facility disposes of a very modern for small animal facility, as well as a external large animal facility (Oberholz, University Leipzig) and a surgery for small and large animals. Furthermore, a broad range of validated SOPs for devices and methods has been implemented.

GLP certificat
© Photo Fraunhofer IZI

Preclinical safety study for the evaluation of biodistribution and tumorigenicity of tissue-engineered human mesenchymal stem cell (MSCs)-based matrix-associated autologous chondrocyte transplantation (MACT) using NSG mice

The development of novel therapies, such as the somatic cell therapy or the transplantation of tissues generated from stem cells, requires new preclinical strategies as to the safety of these products. Conventional efficacy and safety studies, e.g. for biopharmaceuticals, are not suitable for these cell-based products (cell-based advanced therapy medicinal products; ATMPs). The application of cell-based ATMPs thus requires clearly defined safety studies under GLP (Good Laboratory Practice) conditions that are in line with regulatory requirements of the national and european authorities. Here, the interest mainly focusses on biodistribution, i.e. distribution of the applied cell-based ATMPs within the tissue, as well as tumorigenicity, i.e. the propensity of the applied cells to undergo transformation, and thus have to be appropriately addressed in preclinical studies. The aim of this project is the realization of preclinical efficacy and safety studies for a cartilage therapy on the basis of mesenchymal stem cells (MSC). For this ATMP, MSC are isolated in an out-patient bone marrow aspiration and further treated for the production of a patient-specific cartilage therapy (MSC-based Matrix-associated Autologous Chondrocyte Transplantation; MSC-MACT). In the preclinical GLP studies, both the biodistribution and tumorigenic potential of the human MSC-MACT are tested in immunodeficient mice. Due to the immunodeficiency of the animals, the implanted human cells are tolerated without graft rejection, and the migration and/or transformation of the human cells can be analyzed. For an optimal function of the ATMPs, the MSC should remain at the site of implantation and not migrate into the surrounding tissue. Thus, the experimental "biodistribution" part clarifies whether cells migrate from the site of implantation and where they settle in the case of migration. This simultaneously identifies potential sites of tumorigenesis that can arise from implanted cells. In the subsequent experimental part, tumorigenicity of the MSC from the implanted ATMP is tested. The non-clinical safety studies for MSC-MACT are an important regulatory building block on the way to a clinical application, which may significantly reduce the risks of a therapy with MSC-MACT for patients with cartilage defects.

Completed GLP studies

  • Differential protein-biochemical and serological analysis of UV-irradiated and non-irradiated canine thrombocyte concentrates
  • Immunotoxicological in-vitro study of the plant-based immunostimulant mistellectin with intestinal epithelial cells
  • Safety and efficacy studies of MSC-generated cartilage products after autologous implantation in a large animal model (sheep)
  • Safety and efficacy studies of MSC-generated chondrocyte spheroids after implantation in a large animal model (sheep)
  • Preclinical safety study for evaluating the biodistribution and tumorigenicity of tissue-engineered human chondrocyte spheroids in an NSG mouse model

Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).
Zscharnack M, Krause C, Aust G, Thümmler C, Peinemann F, Keller T, Smink JJ, Holland H, Somerson JS, Knauer J, Schulz RM, Lehmann J. J Transl Med. 2015 May 20;13:160. doi: 10.1186/s12967-015-0517-x.
PMID: 25990108

 

Free PMC Article

 

[Strategic considerations on the design and choice of animal models for non-clinical investigations of cell-based medicinal products].
Lehmann J, Schulz RM, Sanzenbacher R. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2015 Nov;58(11-12):1215-24. doi: 10.1007/s00103-015-2239-x. German.
PMID: 26431722

 

Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model.
Pohler P, Lehmann J, Veneruso V, Tomm J, von Bergen M, Lambrecht B, Kohn B, Weingart C, Müller TH, Seltsam A.
Transfusion. 2012 Nov;52(11):2414-26. doi: 10.1111/j.1537-2995.2012.03583.x. Epub 2012 Mar 8.
PMID: 22404822