7: Good Manufacturing Practice-Compliant Processing of Adipose Stromal Cell-based Products in Regenerative Medicine

Subcutaneous fat is emerging as an interesting tissue source for obtaining adipose-derived stromal cells (ASCs) for cellbased therapies in regenerative medicine. The highly heterogeneous, freshly processed stromal vascular fraction (SVF) cells or the expanded adipose-tissue derived mesenchymal stromal cells (MSCs), both are characterised with respect to their regenerative properties. Based on in vitro and preclinical data a number of clinical trials have been initiated to assess their potential clinical benefits. Since basic research is far from the clinical applications, a number of issues emerge and become challenging, when translation of research findings in clinical studies begins. The more progress is achieved with the “bench-to-bedside” approach the more regulatary issues come into place, like: formalities, obligations, regulations, laws and provisions. As there is only limited clinical data available on safety and efficacy, novel cell-based products are highly regulated to assure patient safety and a favorable riskbenefit assessment. To comply with the innovations in regenerative medicine the European Union has classified these novel cell-based drugs as “advanced therapy medicinal products (ATMP).” ATMPs include products derived by gene therapy, somatic cell-based therapy as well as biotechnological therapy, such as tissue engineering. ASCs are considered as ATMPs. In contrast to conventional drugs, ASCs comprise a number of complex biological functions, such as being differentiable, anti-apoptotic, anti-fibrotic, immune regulatory, trophic or pro-regenerative. Nevertheless the regulatory context of ATMPs from preclinical to clinical assessment, to marketing authorisation reclines the authorisation process of classical drugs. This regulatory context also covers the whole manufacturing process from procurement of the tissue, transportation into the manufacturing center, manufacturing, storage, quality control, transport and application to the patient. This cell processing is subsumed under the terms “Good laboratory practice (GLP)” or even “Good manufacturing practice (GMP)” to assure safe and high-quality cell production. Points to consider in the GMP-compliant manufacturing of ASCs will be reviewed in the following.