title: Development of a New Imaging Bulk Package for Multipatient Use in MDCT.
abstract: OBJECTIVE
  Multidose presentations of U.S. Food and Drug Administration (FDA)-approved radiographic contrast agents have been considered pharmacy bulk packages. However, the use of pharmacy bulk packages for multipatient dosing does not meet the U.S. Pharmacopeia definition of a pharmacy bulk package. The purpose of this study was to validate and gain FDA approval for a new multidose preparation of iopamidol for safe, compliant multipatient dosing in the CT suite.
  
  
  METHODS
  An FDA-approved development program was undertaken to determine whether multidose presentations of iopamidol used in combination with a transfer set remain free of chemical and microbiologic contamination during the labeled maximum hold time after container closure penetration and simulated worst-case handling conditions. The program comprised antimicrobial effectiveness testing of iopamidol-300 and iopamidol-370 containers with seven microbes. Microbial growth was evaluated at five time points up to 28 days after introduction. Microbial ingress testing involved inoculation of four challenge sites with each of four microorganisms for up to 14 hours. Chemical compatibility and extractable testing was performed to ensure chemical integrity.
  
  
  RESULTS
  No growth of microorganisms occurred. All evaluated samples remained sterile, indicating no microbial contamination through 14 hours of simulated clinical use. No effect on chemical integrity was found in any of the drawn iopamidol samples meeting the chemical specifications for iopamidol, and no leachable compounds were detected.
  
  
  CONCLUSIONS
  The absence of any chemical or microbiologic contamination led the FDA to approve the iopamidol multidose container and transfer set as a combination product for multipatient use. The approval resulted in a new U.S. Pharmacopeia category of multidose presentation-the imaging bulk package.
authors.affiliation: 1 Global Medical and Regulatory Affairs, Bracco Diagnostics, Inc., Monroe Township, NJ.
authors.forename: Alberto
authors.initials: A
authors.lastname: Spinazzi
authors.affiliation: 2 Global Medical and Regulatory Affairs, Bracco Diagnostics, Inc., Melville, NY.
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Marchildon
authors.affiliation: 2 Global Medical and Regulatory Affairs, Bracco Diagnostics, Inc., Melville, NY.
authors.forename: Elyssa A
authors.initials: EA
authors.lastname: Murray
authors.affiliation: 3 Quality Assurance and Quality Control, Bracco Injeneering SA, Lausanne, Switzerland.
authors.forename: Maud
authors.initials: M
authors.lastname: Giorgi
authors.affiliation: 4 Global Medical and Regulatory Affairs, Bracco Imaging SpA, Via Caduti di Marcinelle, Milan 20134, Italy.
authors.forename: Miles A
authors.initials: MA
authors.lastname: Kirchin
authors.affiliation: 1 Global Medical and Regulatory Affairs, Bracco Diagnostics, Inc., Monroe Township, NJ.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Sireci
mesh_terms: D003287:Contrast Media; D017277:Drug Approval; D004340:Drug Contamination; D004349:Drug Packaging; D006801:Humans; D007479:Iopamidol; D061330:Multidetector Computed Tomography; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D003287:Contrast Media; D007479:Iopamidol
keywords: imaging bulk package; iopamidol; microbiologic contamination; multipatient dosing