Performance Qualification of the robotic system APOTECAunit for non-toxic parenteral preparations

Background and importance
The fully automated robotic system APOTECAunit is designed for the preparation of ready-to-administer (RTA) non-toxic parenteral products in prefilled bags and syringes. Medicinal products used as starting material are dosed volumetrically by 5 mL, 20 mL, and 50 mL syringes, supported by gravimetric in-process control (IPC) of the dosing accuracy.

Aim and objectives
The objective of the study was the performance qualification (PQ) of the APOTECAunit for preparation of RTA bags in series. Dosing accuracy was tested with each of the available dosing syringes.

Materials and methods
Test solutions were prepared by the APOTECAunit using bupivacaine-HCl 20 mg/mL, 100 mL and prefilled 50 mL or 500 mL 0.9% NaCl infusion bags as starting material. For dosing, 5 mL, 20 mL (dosing device ASN-05, ASN-20, Loccioni, Italy), and 50 mL (Original Perfusor^® Syringe 50 mL, B.Braun Melsungen AG, Germany) syringes were used. 1 mL, 2 mL (5 mL dosing device), 6 mL (20 mL dosing device), 35 mL (50 mL syringe) of bupivacaine-HCl concentrate were injected into prefilled 50 mL or 500 mL bags to reach a final concentration of 0.36 mg/mL, 0.71 mg/mL, 2.0 mg/mL, 1.25 mg/mL bupivacaine-HCl. 20 bupivacaine-HCl RTA bags of each concentration were prepared on three different days (in total 20x4x3). In each test solution, the bupivacaine-HCl concentration was determined by a validated RP-HPLC method. Dosing accuracy was calculated by the experimentally determined bupivacaine-HCl concentrations related to the nominal concentrations. The gravimetric in-process control (IPC) data were retrieved from the APOTECAunit and dosing accuracy evaluated.

Results
Measured bupivacaine-HCl concentrations amounted to 0.37 mg/mL ± 0.79 % (dose 1 mL), 0.70 mg/mL ± 0.82 % (dose 2 mL), 1.95 mg/mL ± 1.75 % (dose 6 mL), and 1.25 mg/ml ± 1.10 % (dose 35 mL). The dosing accuracy was 0.33 % (1 mL), -1.17 % (2 mL), -4.54% (6 mL) and -0.31 % (35 mL).
Based on the gravimetric IPC of the APOTECAunit the dosing accuracy was 0.81 % (1 mL), 0.97 % (2 mL), 1.01 % (6 mL), and 0.61 % (35 mL).

Discussion and Conclusion
The APOTECAunit passed the PQ tests for bupivacaine-HCl RTA bags. The 5 mL dosing devices proved to be suitable for dosing of minimal 1 mL doses, the 20 mL dosing device minimal 6 mL doses, the 50 mL syringe minimal 35 mL. Results of the gravimetric IPC are reliable.

See the poster