Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience.
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.
Gee
Adrian P
AP
Center for Cell and Gene Therapy, Baylor College of Medicine, MC3-3320, Feigin Center, 102 Bates Street, Houston, TX 77030, USA.
Richman
Sara
S
Durett
April
A
McKenna
David
D
Traverse
Jay
J
Henry
Timothy
T
Fisk
Diann
D
Pepine
Carl
C
Bloom
Jeannette
J
Willerson
James
J
Prater
Karen
K
Zhao
David
D
Koç
Jane Reese
JR
Ellis
Steven
S
Taylor
Doris
D
Cogle
Christopher
C
Moyé
Lemuel
L
Simari
Robert
R
Skarlatos
Sonia
S
D057205:Automation, Laboratory; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods / Q000592:standards*; D002469:Cell Separation / Q000379:methods; D064987:Cell- and Tissue-Based Therapy / Q000191:economics / Q000592:standards*; D005434:Flow Cytometry; D006801:Humans; D059021:Laboratory Proficiency Testing; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017410:Practice Guidelines as Topic; D011786:Quality Control; D044968:Regenerative Medicine / Q000379:methods; D054928:Validation Studies as Topic