The Quality Management Ecosystem in Cell Therapy in Catalonia (Spain): An Opportunity for Integrating Standards and Streamlining Quality Compliance.

Cell therapies are required to meet with compulsory regulations that co-exist with other optional standards and guidelines that together compose a complex quality management system. Indeed, reliable insights on the mechanisms of action and safety of novel cell-based therapies require adherence to solid quality management structures in all steps of the value chain, from early research and tissue procurement to clinical trials and biovigilance, thus guaranteeing reproducibility and solid foundations for better science and improved clinical practice. Herein we present the concept of the quality ecosystem as a tool to understand and assist all stakeholders involved in developing and structuring the integration of standards as novel developments are taking place. We conclude that the various quality management initiatives can all be thought about under the umbrella of an ecosystem.

Utility of routine evaluation of sterility of cellular therapy products with or without extensive manipulation: Best practices and clinical significance.

BACKGROUND: We analyzed the results of routine sterility testing performed in our center over the last 10 years, in the context both hematopoietic stem cell transplantation (HSCT) and Advanced Therapeutic Medicinal Products (ATMPs). METHODS: For sterility tests 14-day cultures were performed in culture media detecting aerobic and anaerobic microorganisms. RESULTS: In this study, 22/1643 (1.3%) of apheretic products for autologous or allogeneic HSCT were contaminated, whereas 14/73 bone marrow (BM) harvests (17.8%) were positive. In 22 cases, the contaminated HSCs were infused to patients, but there was no evidence of any adverse impact of contamination on the hematologic engraftment or on infections. Indeed none of the five positive hemocultures detected in patients following infusion could be linked to the contaminated stem cell product. Our Cell Factory also generated 286 ATMPs in good manufacturing practice (GMP) conditions since 2007 and all final products were sterile. In three cases of mesenchymal stromal cell expansions, the starting BM harvests were contaminated, but the cell products at the end of expansion were sterile, presumably thanks to the presence of an antibiotic in the culture medium. DISCUSSION: The decreased rate of contamination of cell harvests observed with time suggests that routine sterility testing and communication of the results to the collecting centers may improve clinical practices. Furthermore, we recommend the use of antibiotics in the medium for ATMP expansion, to decrease the likelihood of expanding microorganisms within clean rooms. Finally we discuss the costs of sterility testing of ATMPs by GMP-approved external laboratories.