Abstract
Background aims. Multicenter cellular therapy clinical trials require the establishment and implementation of standardized cell-processing protocols and associated quality control (QC) mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients. Methods. Standardized cell preparations, consisting of autologous bone marrow (BM) mononuclear cells, prepared using a Sepax device, were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central QC program that included product evaluation by the CCTRN biorepositories. Results. Data from the first 60 procedures demonstrated that uniform products, that met all release criteria, could be manufactured at all five sites within 7 h of receipt of BM. Uniformity was facilitated by use of automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized QC. Conclusions. Complex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training and QC.
Acknowledgements
This study was supported by grant number U01-HL-087318 from NHLBI. It was also supported in part by NHLBI contract numbers N01-HB-37164 (Molecular and Cellular Therapeutics Facility, University of Minnesota) and N01-HB-37163 (Cellprocessing facility, Baylor College of Medicine) from the National Heart and Blood Institute. Validation and qualification data on the use of the Sepax device were generated under a CCTRN subcontract by John McMannis PhD of the Department of Blood and Marrow Transplant at the MD Anderson Cancer Center, Houston, Texas.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.