Determination of the cross-contamination and validation of the cleaning process for an automated personalised dosing system

Objective

To determine the degree of cross-contamination and to validate a cleaning process for an Automated Personalised Dosing System (APDS), respecting the permitted residue transfer limits.

Method

An analytical determination by high pressure liquid chromatography with mass spectrometry was performed for 11 drugs considered critical for their potential for contamination, toxicity (National Institute for Occupational Safety and Health (NIOSH) List 2016) and/or narrow therapeutic index. The test was carried out for three consecutive weeks, seven repetitions per week, in a state of maximum contamination and maximum cleanliness. The main validation criterion of the cleaning protocol was to quantify that the active ingredients measured were below the Permitted Daily Exposure index or fraction 1/1000 of the minimum daily dose, both in a state of maximum contamination and when the APDS is in a clean condition, for an average number of tablets consumed per person per day.

Results

In all the samples analysed, some compound could always be quantified below 2% of the permitted transfer limits, highlighting the presence of paracetamol and carbamazepine. In the state of maximum contamination, the mean±SD values of paracetamol and carbamazepine were 5.83±1.56 µg and 0.22±0.07 µg, respectively, without significant differences in mean values over the 3 weeks of the study. After the cleaning protocol was executed, only paracetamol and carbamazepine were detected, with the average values being 4.67 µg (95% CI 3.92 to 5.43, p<0.05) and 0.07 µg (95% CI 0.03 to 0.10, p<0.05) lower than the state of maximum contamination, respectively.

Conclusions

In all cases the level of cross-contamination for an APDS was below the pre-established limits. The cleaning protocol has been validated, confirming APDS decontamination of the most critical medicines.