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

Abstract

BACKGROUND Cellular therapy studies are often conducted at multiple clinical sites in order to accrue larger patient numbers. In many cases this necessitates use of localized Good Manufacturing Practices (GMP) 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 (ABMMC) to treat myocardial infarction and heart failure. STUDY DESIGN Factors affecting cell manufacturing time were studied in 269 patients enrolled on 3 CCTRN protocols using Sepax-separated ABMMC. The cells were prepared at 5 GMP 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 seven hours. Contributing to this were incoming testing and device preparation, release testing, patient randomization and product delivery. The average out-of body-time (OBT), which was to be <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.

Spanish Cell Therapy Network (TerCel): 15 years of successful collaborative translational research

“…However, this background has fostered single-institutionÀbased experiences and small phase 1 and 2 clinical trials instead of a coordinated approach leading to large phase 2 and 3 trials, at least at the national level. It is clear that collaborative efforts in this new area of translational research will be needed to achieve the global aim of transferring these treatments from the bench to the bedside within the shortest possible time [3,4]. But, as indicated, there are only a small number of published phase 3 trials and very few cell therapy products have reached the final process of authorization by the regulators.…”

Dr. Sonia Skarlatos and the National Heart, Lung, and Blood Institute Translational Research and Resource Programs

“…A quality assurance group was established with PACT and CCRTRN personnel for these trials in order to train staff, conduct site visits, and review all trial documentation. As part of the review process, this group tracked the times taken for the various components of marrow harvesting, transportation, processing, release testing, randomization, placebo preparation, and return to the clinical center for administration to the trial participant (Richman et al, 2012). Although the technical cell processing procedure takes only 90 min, the total time for processing was approximately 7 hours.…”