To flip or not to flip : toward a change in pratices ?

Objective
According to local practices, the removal of flip-off caps (FOC) from vials of cytotoxic drugs can be done either outside or inside the isolator. The objective of this study is to determine whether the sterilizing agent (hydrogen peroxide) effectively penetrates under the FOC to eliminate any potential microbiological contamination.

Materiel and methods
Twenty vials of injectable drugs with heterogeneous FOC diameters were selected. The vials were identified from 1 to 20 according to INN, the color and the FOC diameter. The diameters were 8 mm for 9 FOC, 18 mm for 3 FOC, and 22 mm for the remaining 8. The vials were immersed in an aqueous solution contaminated with environmental bacteria for 12 hours. After complete drying of the outside of the vials for 12 hours, they were then decontaminated and disinfected according to standard procedures. The vials and the necessary sampling material were then sterilized using a qualified isolator located in a disused controlled atmosphere area. Two types of samples were taken : TSA contact plates and swabs. In the isolator, the 20 FOC were placed on 4 contact plates : one plate with FOC from vials 1 to 4, one for vials 5 to 8, one for vials 9 to 15, and one for vials 16 to 20. The swabs were used to sample the septum of the vials after removal of the FOC. Positive and negative controls were conducted.

Results
After 7 days of incubation, the negative control showed no contamination. The positive control revealed a count of over 100 CFU/25cm², without identifying a specific pathogen.
Of the 20 swabs taken, 9 returned positive. Stenotrophomonas maltophilia (Gram-negative bacillus) was identified in vials 1 to 6 and 8. Staphylococcus warneri (Gram-positive cocci) was identified in vial 9, and Staphylococcus pasteuri (Gram-positive cocci) was identified in vial 20.
All contact plates corresponding to the positive swabs were also contaminated. Seven of the FOC tested positive had a diameter of 22 mm, one had a diameter of 18 mm, and one had a diameter of 8 mm. The remaining 11 FOC were tested negative ; most of them had a diameter of 8 mm (8 FOC), 2 had a diameter of 18 mm, and 1 had a diameter of 22 mm.

Discussion / Conclusion
In conclusion, the sterilizing agent does not effectively penetrate under the FOC of the vials. If contamination is initially present on the septum, there is a risk of contaminating our sterile enclosures when the FOC is removed. It was observed that the sterilizing agent penetrates more effectively under FOC of smaller diameter compared to larger one.
Further work on the permeability of FOC to sterilizing agents could be undertaken by manufacturers to reduce the risk of microbiological contamination in our sterile enclosures.