Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study.

The objective of this randomized, prospective and controlled study was to investigate the ability of a closed-system transfer device (CSTD; BD-Phaseal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices.The 6-month study started with the opening of a new compounding unit. Two isolators were set up with 2 workstations each, one to compound with standard devices (needles and spikes) and the other using the Phaseal system. Drugs were alternatively compounded in each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxorubicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Significance was defined for p<0.05. Overall contamination was lower in the "Phaseal" isolator than in the "Standard" isolator (12.24% vs. 26.39%; p < 0.0001) although it differed according to drug. Indeed, the contamination rates of gemcitabine were 49.3 and 43.4% (NS) for the Standard and Phaseal isolators, respectively, whereas for ganciclovir, they were 54.2 and 2.8% (p<0.0001). Gemcitabine amounts were 220.6 and 283.6 ng for the Standard and Phaseal isolators (NS), and ganciclovir amounts were 179.9 and 2.4 ng (p<0.0001).This study confirms that using a CSTD may significantly decrease the chemical contamination of barrier isolators compared to standard devices for some drugs, although it does not eliminate contamination totally

Assay characteristics for the ten tested drugs.

<p>Assay characteristics for the ten tested drugs.</p

Contamination measured for worktop before cleaning process.

<p>Results for contamination rates are presented as number of positive samples/number of measured samples (n/N) and in %. Drug amounts are expressed in ng/cm². Drugs are classified according to the frequency of positive samples in the Standard group.</p

Contamination measured for window before cleaning process.

<p>Results for contamination rates are presented as number of positive samples/number of measured samples (n/N) and in %. Drug amounts are expressed in ng/cm². Drugs are classified according to the frequency of positive samples in the Standard group.</p

BD-Phaseal assessment throughout the study.

<p>Global impression (a), Feeling of safety (b), Encumbrance (c) and Comparison to the reference method (d) are represented. The assessments were made according to a 5-point Likert’s scale. A plot represents the mean and error bars the standard deviation.</p

Antineoplastic drug contamination rate of the barrier isolators before cleaning procedure.

<p>Histograms represent the proportion of positive samples including traces. Error bars represent the confidence intervals.</p

Scheme of the isolators and biodecontamination systems.

<p>The two isolators have two workstations each. In one isolator (Standard devices), the preparations are compounded only with spikes and needles. In the other isolator (Phaseal), the compounding process involves only Phaseal devices. Three biodecontamination systems are connected to the isolators. Sterilization is performed with hydrogen peroxide. The central biodecontamination system is an aeraulic barrier. There is no airflow between the two isolators.</p

Comparison of contamination rates (in %) and contamination amounts (in ng) between Standard and Phaseal devices according to drug.

<p>Contamination rates are computed taking traces into account. Contamination amounts correspond to the cumulative amount per sampling day.</p

Contamination measured for gloves before cleaning process.

<p>Results for contamination rates are presented as number of positive samples/number of measured samples (n/N) and in %. Drug amounts are expressed in ng/glove. Drugs are classified according to the frequency of positive samples in the Standard group.</p

Compounding activity for the ten drugs studied throughout the study.

<p>Data correspond to the number of preparations (N) and prepared doses for each of the 10 studied drugs. Doses are expressed in mg and are presented as mean±standard deviation.</p