title: Sterility testing of cell therapy products: parallel comparison of automated methods with a CFR-compliant method.
abstract: BACKGROUND
  Automated blood culture systems are not FDA-approved for sterility testing of human cells, tissues, or cellular- or tissue-based products. It was previously demonstrated that BacT/ALERT (bioMérieux) and Bactec (Becton Dickinson) were superior to the manual CFR method described in the general biologics regulations, in rates of detection and time to detection of organisms seeded into mock mononuclear cell products with a variety of background media and antibiotics. In this study, the two automated systems were compared to the CFR method for sterility testing of actual cell therapy products manufactured in our facility.
  
  
  METHODS
  Over a 36-month period, in-process and final product samples from all cell therapy products manufactured in our facility were tested for sterility both by the CFR method and by either BacT/ALERT or Bactec. Products were categorized according to collection and processing variables for analysis of results.
  
  
  RESULTS
  For 1617 samples of a broad range of cell therapy products, rates of true-positive tests were comparable for the automated and CFR methods (2.3% vs. 2.1%), but the CFR method had higher rates of false-positive results (7.3% vs. 0.2%). For automated systems, time to detection of organisms was equivalent to, or faster than, the CFR method.
  
  
  CONCLUSIONS
  Compared to the CFR method, both BacT/ALERT and Bactec are more sensitive, faster in time to detection, less prone to false-positive results, and less labor-intensive. Both of these automated systems are suitable for sterility testing of cell therapy products after site-specific validation has been performed.
authors.affiliation: Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. hkhuu@mail.cc.nih.gov
authors.forename: Hanh M
authors.initials: HM
authors.lastname: Khuu
authors.forename: Nayana
authors.initials: N
authors.lastname: Patel
authors.forename: Charles S
authors.initials: CS
authors.lastname: Carter
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Murray
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Read
mesh_terms: D001331:Automation; D001419:Bacteria / Q000302:isolation & purification*; D018929:Cell Culture Techniques; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D005189:False Positive Reactions; D006801:Humans; D012680:Sensitivity and Specificity; D013242:Sterilization / Q000379:methods* / Q000592:standards