Assessment of the contamination risk in an automated system for the repackaging of oral liquid medications (ADP-20L)

Objective
The ADP-20L automated system enables the repackaging of oral liquid medications from up to 20 multidose bottles into unit-dose cups. This study aimed to assess the risk of contamination when different medications are simultaneously repackaged under worst-case conditions.

Materials and method
The ADP-20L was configured to alternately prepare a cup containing fluorescein followed by a cup containing the matrix only from reservoirs placed opposite each other on the carousel. Three representative matrices were selected to mimic different types of oral liquid medications: water for injection (WFI) for aqueous formulations, 70% glucose (G70) for viscous formulations, and a mixture of water and polysorbate 80 (WFI/P80; 80%/20%) for foaming formulations. For each matrix, 10 fluorescein-containing cups and 10 matrix-only cups were prepared. Fluorescein contamination was assessed in the 30 matrix-only cups using a high performance liquid chromatography coupled with a fluorescence detection (Limit of detection= 0.015 ng/mL).
Filling conditions were intentionally set to represent a worst-case scenario (non-optimized filling parameters of 25 000µL using a large needle) to maximize splashes and potential contamination. Visual inspection for splashes was performed by two operators.

Results/Discussion
Significant splashes (droplet count > 10) were observed when filling WFI and WFI/P80. Droplets reached the platform surrounding the filling position and the area beneath the platform. In contrast, filling G70 generated minor splashes (0-1 droplet), with a single droplet observed in 6 out of the 10 cups. The higher viscosity of G70 reduced droplet formation, thereby limiting splashes.
Despite the extensive splashes observed with aqueous products, no fluorescein contamination was detected in any matrix-only cup (< 0.015 ng/mL). Carousel rotation did not generate any detectable splashes.

Conclusion
Although no contamination between products was detected, the observed splashes resulted in surface contamination. These findings highlight the need to optimize filling parameters and operating conditions to reduce the risk of splashes, and to develop and validate and effective cleaning procedure.

Keywords: automation, high performance liquid chromatography, equipment contamination