2012|13 Annual Report Fraunhofer IGB

68 Process development for the production of “Advanced Therapy Medicinal Products” (ATMPs) The advances in the development and wider use of novel cell therapies, tissue engineering and regenerative medicine have led in recent years to an extension of the term “medicinal”, which has equated to a modiﬁcation of the legal regulation of these products. Cells or tissues that are used to treat people were placed in a new product group that is summarized by EU Regulation EC No. 1394/2007 for advanced therapy medicinal products (ATMP). The GMP (good manufacturing practice) unit at the Fraun- hofer IGB develops and validates new and sometimes complex production processes for innovative cell therapies and tissue- engineered products to gain regulatory approval for the pro- duction of clinical trial material as well as the production of sufﬁcient ATMP material to allow our partners to employ their therapies in a clinical setting. Bioartiﬁcial tissue reconstruction for tracheal surgery The aim of this project, funded by the Federal Ministry of Edu- cation and Research (BMBF), is to develop a manufacturing process and the clinical testing of a novel implant for the re- construction of rare respiratory defects. The implant consists of a vascularized porcine support scaffold (BioVaSc, biological vascularized scaffold) and the patient’s own (autologous) cells. For the development of a GMP process, the preparation meth- od of the BioVaSc was optimized. To ensure product quality, in particular the viral safety of the animal starter material, suit- able methods for the analysis of the cell, DNA and endotoxins were established. For the colonization of the BioVaSc with au- tologous ﬁbroblasts, endothelial and muscle cells, we devel- oped GMP-compliant protocols. After a four-week period of cell expansion, the cells are introduced into the matrix of the BioVaSc. The microvascular endothelial cells colonize the vas- cular structures, while the skeletal muscle cells and ﬁbroblasts grow in the intestinal lumen of the BioVaSc. The subsequent two-week aging of the scaffold takes place in a specially de- signed bioreactor system, which allows the culture and par- ticularly the maturation of the blood vessels under physiologi- cal conditions. Following issuance of manufacturing license for such implants by the competent authority, the BioVaSc should be tested in a clinical phase I study. Insulin-producing cells for the treatment of type 1 diabetes The Fraunhofer IGB is developing a GMP-compliant process for the production of insulin-producing cells from the patient’s own liver cells for the US company Orgenesis. Before these cells can be tested in an initial clinical trial as a treatment for type 1 diabetes, the manufacturing process based on the ofﬁ- cial regulations for ATMPs and cell transplants must be stand- ardized to ensure safety and reproducibility. The cause of type 1 diabetes is the gradual loss of all the beta cells of the “islets of Langerhans”, which produce insulin in the pancreas. A possible cure for diabetes could be the re- placement of the diseased beta cells with healthy pancreatic tissue. Such transplants of pancreas or islet cells are currently being investigated in clinical trials. In order to avoid the rejec- tion of the transplant by the immune system of the recipient, MEDICINE INNOVATIVE CELL AND TISSUE THERAPIES ON THE WAY INTO CLINICAL APPLICATION Dr. rer. nat. Martin Funk, Dipl.-Biol. (t. o.) Iris Dally 1 2

2012|13 Annual Report Fraunhofer IGB

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