Development of a New Imaging Bulk Package for Multipatient Use in MDCT.

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. MATERIALS AND 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. CONCLUSION: 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.

Evaluation of the effects of strain-specific antigen variation on the accuracy of serologic diagnosis of Helicobacter pylori infection.

It has been suggested that enzyme immunoassay (EIA) kits validated in one region may yield variable diagnostic performance results in different regions, possibly due to strain-specific differences in antibody responses in different populations. We tested (13)C-urea breath test-characterized serum samples from 109 U.S. patients and 288 Japanese patients using enzyme immunoassay with different preparations of high-molecular-weight cell-associated (HM-CAP) antigens that are conserved across Helicobacter pylori strains. Replicate antigens were prepared from five H. pylori clinical isolates. Eight antigen preparations were evaluated: two of U.S. origin and six of Japanese origin. The accuracies achieved with the eight antigen preparations ranged from 94.4 to 96.3% with the U.S. samples. With the Japanese samples the accuracies achieved ranged from 92.3 to 97.2%. Use of a pool of HM-CAP antigens prepared from isolates from Japan resulted in a higher median enzyme immunoassay value and slightly fewer samples with indeterminate results compared to the results obtained by use of the U.S. standard HM-CAP antigen for H. pylori-positive patients (accuracies, 97.2 and 92.3%, respectively), suggesting that variations in performance between both antigen source and patient population might be reduced by using antigens pooled from several strains.