Factors affecting the turnaround time for manufacturing, testing, and release of cellular therapy products prepared at multiple sites in support of multicenter cardiovascular regenerative medicine protocols: A Cardiovascular Cell Therapy Research Network (CCTRN) study

BACKGROUND: Cellular therapy studies are often conducted at multiple clinical sites to accrue larger patient numbers. In many cases this necessitates use of localized good manufacturing practices facilities to supply the cells. To assure consistent quality, oversight by a quality assurance group is advisable. In this study we report the findings of such a group established as part of the Cardiovascular Cell Therapy Research Network (CCTRN) studies involving use of autologous bone marrow mononuclear cells (ABMMCs) to treat myocardial infarction and heart failure. STUDY DESIGN AND METHODS: Factors affecting cell manufacturing time were studied in 269 patients enrolled on three CCTRN protocols using automated cell processing system (Sepax, Biosafe SA)-separated ABMMCs. The cells were prepared at five good manufacturing practices cell processing facilities and delivered to local treatment sites or more distant satellite centers. RESULTS: Although the Sepax procedure takes only 90 minutes, the total time for processing was approximately 7 hours. Contributing to this were incoming testing and device preparation, release testing, patient randomization, and product delivery. The mean out-of-body time (OBT), which was to be less than 12 hours, averaged 9 hours. A detailed analysis of practices at each center revealed a variety of factors that contributed to this OBT. CONCLUSION: We conclude that rapid cell enrichment procedures may give a false impression of the time actually required to prepare a cellular therapy product for release and administration. Institutional procedures also differ and can contribute to delays; however, in aggregate it is possible to achieve an overall manufacturing and testing time that is similar at multiple facilities.