title: Catastrophic failures of freezing bags for cellular therapy products: description, cause, and consequences.
abstract: BACKGROUND
  Container integrity is critical for maintaining sterility of cryopreserved cellular therapy products. We investigated a series of catastrophic bag failures, first noticed in early 2001.
  
  
  METHODS
  Process records were reviewed for all PBPC and lymphocyte products cryopreserved in bags from January 2000 through April 2002. Patient charts were also reviewed.
  
  
  RESULTS
  One thousand two hundred and four bags were removed from storage for infusion to 261 patients. All products had been cryopreserved in Cryocyte poly(ethylene co-vinyl acetate) (EVA) bags in either 10% DMSO or 5% DMSO and 6% pentastarch. Product volumes were 25-75 mL, and bags were stored with overwrap bags in a liquid nitrogen tank. From January 2000 to April 2001, failure occurred in 10 of 599 (1.7%) bags. From May 2001 to April 2002, 58 of 605 (9.6%) bags failed, typically with extensive fractures that were visible before thaw. Of the 58 that failed, 24 were salvaged by aseptic methods and infused to patients under antibiotic coverage; 10 of those 24 (42%) had positive bacterial cultures. Bag failures were not related to product type, cryoprotectant solution, liquid versus vapor storage, or freezer location. Failures were linked to use of four Cryocyte bag lots manufactured in 2000 and 2001. After replacing these lots with a 1999 Cryocyte lot and with KryoSafe polyfluoroethylene polyfluoropropylene (FEP) bags, no more failures occurred in 75 and 102 bags, respectively, thawed through April 2002.
  
  
  CONCLUSIONS
  High rates of bag failure were associated with four Cryocyte bag lots. No serious adverse patient effects occurred, but bag failures led to microbial contamination, increased product preparation time, increased antibiotic use, and increased resource expenditure to replace products.
authors.affiliation: Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Khuu
authors.forename: H
authors.initials: H
authors.lastname: Cowley
authors.forename: V
authors.initials: V
authors.lastname: David-Ocampo
authors.forename: C S
authors.initials: CS
authors.lastname: Carter
authors.forename: C
authors.initials: C
authors.lastname: Kasten-Sportes
authors.forename: A S
authors.initials: AS
authors.lastname: Wayne
authors.forename: S R
authors.initials: SR
authors.lastname: Solomon
authors.forename: M R
authors.initials: MR
authors.lastname: Bishop
authors.forename: R M
authors.initials: RM
authors.lastname: Childs
authors.forename: E J
authors.initials: EJ
authors.lastname: Read
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001207:Asepsis / Q000295:instrumentation / Q000379:methods; D001407:Bacillus / Q000302:isolation & purification; D002648:Child; D003352:Corynebacterium / Q000302:isolation & purification; D015925:Cryopreservation / Q000295:instrumentation* / Q000379:methods* / Q000706:statistics & numerical data; D004866:Equipment Contamination / Q000191:economics / Q000706:statistics & numerical data; D004868:Equipment Failure / Q000706:statistics & numerical data; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods / Q000706:statistics & numerical data; D010969:Plastics / Q000378:metabolism / Q000627:therapeutic use; D013210:Staphylococcus / Q000302:isolation & purification; D013234:Stem Cells / Q000378:metabolism* / Q000382:microbiology; D014021:Tissue Preservation / Q000295:instrumentation / Q000379:methods / Q000706:statistics & numerical data; D020858:Tissue and Organ Harvesting / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D018952:Antigens, CD34; D010969:Plastics