Preliminary evaluation of the detectability potential of visible particles: comparison between a candling table in accordance with the European Pharmacopoeia and a polarized light table

Introduction
The visual inspection of injectable drugs (candling) is a quality control assay to verify the absence of visible particles that may contaminate injectable preparations. While most hospitals perform this test using a candling table (CT) recommended by the European Pharmacopoeia (EP), other equipment exists, such as polarized light candling tables (PLT). The objective of this work was to compare the particle detection capability between these two types of equipment.

Materials/Methods
A kit of 30 amber glass vials consisting of 25 vials free of particles and 5 vials with particles was prepared. The vials with particulate matter contained glass (micro shards obtained by crushing), plastic (micro-splinters), dust, paper fibres (syringe sterilization bags or other preparation or packaging devices) and a chemical precipitate (obtained by mixing silver nitrate with 0.9% sodium chloride saline solution). The vials of each kit were each blinded and randomly examined by three different operators under three conditions: light intensity of 2000-3750 lux (CT1, according to EP specifications) and 3050-6200 lux (CT2, highest possible intensity) and PLT. For each condition, sensitivity (Se), specificity (Sp), and positive or negative predictive values (PPV and NPV) were calculated.

Results
87% of contaminated samples were intercepted with PLT, compared with 67 and 73% in the CT1 and CT2 groups, respectively. All the samples contaminated with paper fibres were intercepted. The most difficult contaminations to visualize were glass (one third of operators in the PLT group versus two thirds in the CT groups) and dust, which was not spotted by any operator in the CT1 group, one third in the CT2 group and all in the PLT group. Only one operator did not spot the plastic particles and the precipitate with CT1 and CT2, respectively (none in the PLT group). In the end, candling of vials with the PLT allowed the best Se (0.87), Sp (1.00), PPV (1.00) and NPV (0.97). Conversely, in the CT1 group, lower values with Se at 0.65, PPV at 0.89 and NPV at 0.93 but equivalent Sp (0.99) were obtained. By increasing brightness (CT2), Se increased (0.73) with relatively equivalent Sp and NPV (0.96 and 0.94), but PPV decreased (0.80). Furthermore, the operators noted that the presence of bubbles was much more visible during candling on the CT than on the PLT.

Discussion/Conclusion
In this preliminary study, the PLT appears to be a more sensitive candling method than the CT, at both the EP recommended light intensity and at a highest intensity. Dust particles appear to be particularly more difficult to visualize with the CT than with the PLT. The gas bubbles, very visible during the candling with the CT, could alter the visualization of particles present. On the contrary, the glass particles were more intercepted with the CT, therefore the profile of visualized particles seems to be different between the CT and the PLT.

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