# Performance Qualification of Automatic System for Antineoplastic Preparation
## 3 Results and Discussion  
The data obtained by the analytical laboratory using the UHPLC-HRMS system were compared with the theoretical dosages. All the samples have met the acceptance criteria of \(\pm 10\%\) (Table 5). Therefore, the PHARMODUCT(r) automated system has demonstrated high reliability in the filling accuracy of multidose bags and especially final containers. The data collected showed that when filling the final containers with the three drugs under study, considered representative by formulation (liquid/powder) and by different densities, the maximum total mean deviation was 2.138 g, equal to 0.49% of the expected values, for the drug paclitaxel. The maximum mean deviations obtained during dispensing of the other drugs \begin{table}
\begin{tabular}{c c c c} \hline \hline
**DRUG** & \
\begin{tabular}{c} **Theoretical** \\ **Concentration** \\ \end{tabular} &
\begin{tabular}{c} **Found** \\ **Concentration** \\ \end{tabular} & **Error** \\ \hline Run1\_1 5-Fluorouracil & 20 mg/mL & 19.45 mg/mL & 2.75\% \\ Run1\_2 5-Fluorouracil & 20 mg/mL & 20.75 mg/mL & 3.75\% \\ Run2\_3 5-Fluorouracil & 4 mg/mL & 3.71 mg/mL & 7.25\% \\ Run2\_4 5-Fluorouracil & 4 mg/mL & 3.70 mg/mL & 7.50\% \\ Run3\_1 5-Fluorouracil & 4 mg/mL & 3.83 mg/mL & 4.25\% \\ Run3\_3 5-Fluorouracil & 8 mg/mL & 7.67 mg/mL & 4.13\% \\ \hline Run1\_1 Cyclophosphamide & 6 mg/mL & 6.36 mg/mL & 6\% \\ Run1\_2 Cyclophosphamide & 6 mg/mL & 6.26 mg/mL & 4.33\% \\ Run2\_3 Cyclophosphamide & 2.40 mg/mL & 2.43 mg/mL & 1.25\% \\ Run2\_4 Cyclophosphamide & 2.40 mg/mL & 2.24 mg/mL & 6.67\% \\ Run3\_1 Cyclophosphamide & 2.40 mg/mL & 2.25 mg/mL & 6.25\% \\ Run3\_3 Cyclophosphamide & 3.2 mg/mL & 3.44 mg/mL & 7.50\% \\ \hline Run1\_1 Paclitaxel & 0.70 mg/mL & 0.68 mg/mL & 2.86\% \\ Run1\_2 Paclitaxel & 0.70 mg/mL & 0.68 mg/mL & 2.86\% \\ Run2\_3 Paclitaxel & 0.30 mg/mL & 0.32 mg/mL & 6.67\% \\ Run2\_4 Paclitaxel & 0.30 mg/mL & 0.29 mg/mL & 3.33\% \\ Run3\_1 Paclitaxel & 0.30 mg/mL & 0.32 mg/mL & 6.67\% \\ Run3\_3 Paclitaxel & 0.30 mg/mL & 0.31 mg/mL & 3.33\% \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Comparison of theoretical and found concentrations with relative percentages of deviation. studied were \(-0.854\) g or \(-0.34\%\) of expected values for cyclophosphamide and \(-0.190\) g or \(-0.07\%\) of expected values for 5-fluorouracilacil. Preparations made with these drugs were compared with filling tests using water in-stead of the drug. The maximum average percentage obtained was 0.47%, a value comparable to that obtained in the trials with the drug. All final preparations were weighed using a reference scale (manufacturer Sartorius, model MCE12025-2500-S0, accuracy of 0.01 g) with a valid calibration certificate. Figure 7 shows the processed data on the conducted trials. For each drug, the deviations measured from the required quantities are expressed by quantity (g) and percentage (%). In addition, with regard to cyclophosphamide, the last bags dispensed for each run at high, low and random dosages, chosen as the worst case for sterility testing and bacterial endotoxin determination, were found to comply with the defined acceptance criteria, as well as being sterile and with an endotoxin content of less than 0.625 EU/mL. As for the media fill test, no signs of microbiological growth were observed after the 14-day incubation period (7 days at 22.5 \({}^{\circ}\)C and 7 days at 32.5 \({}^{\circ}\)C). Furthermore, by studying the pressure difference between the system and the clean room, a value of \(-97.56\) Pa was recorded. The negative pressure of the main chamber of the automatic system was also demonstrated by the Draeger tube visual test. In fact, visible white smoke, generated from the clean chamber part, entered the chamber. At last, the hourly leak rate (h\({}^{-1}\)) showed a value of 0.002033 h\({}^{-1}\) (according to acceptance criteria of ISO-10648-2 [28]). The pressure and temperature values at 15-min intervals are shown in Table 6.  
Figure 7: Statistical data related to total mean deviation.