Objectives The implementation of dose-banding (DB) in centralised, pharmacy-based cytotoxic drug preparation units allows the preparation of standardised doses in series. The aim of this study was to evaluate the feasibility of DB for the prescribing of ganciclovir (GV) infusion solutions and to investigate the microbiological stability of dose-banded, automatically prepared readyto-administer GV infusion bags by media-fill simulation tests and sterility tests. Methods The frequency of prescription of GV doses was retrospectively analysed before and after implementing the DB scheme. Four dose-ranges or 'bands' and the corresponding standard doses (250, 300, 350, 400 mg) were identified. The maximum variance was set at ±10% of the individually prescribed dose. The aseptic preparation of a series of GV infusion bags was simulated with double strength tryptic soy broth as growth medium and prefilled 0.9% NaCl polyolefin infusion bags as primary packaging materials. The simulation process was performed with the APOTECAchemo robot on five consecutive days. In total, 50 infusion bags were filled, incubated and stored for 12 weeks at room temperature. The media-filled bags were visually inspected for turbidity after 2, 4, 8, 10 and 12 weeks. Following incubation, growth promotion tests were performed. During the simulation tests, airborne contamination was monitored with settle plates and microbial surface contamination with contact plates. Pooled sterility tests were performed for a series of 10 standard GV infusion bags after a 12-week storage period under refrigeration (2 °C-8 °C). results After implementation of the DB scheme, about 60% of the prescribed GV doses were prepared as standard preparations by the robotic system. The number of different GV doses was reduced by 61.8% (76 vs 29). None of the 50 media-filled bags showed turbidity after a storage period of 12 weeks, indicating the absence of microorganisms. The environmental monitoring with settle/contact plates matched the recommended limits set for cleanroom Grade A zones, except in the loading area of the robot. Media fills used for the sterility tests remained clear during the incubation period, thereby revealing sterility. Positive growth promotion tests proved the process's reliability. Conclusions A DB scheme for prescribing and preparation of standard GV infusion bags was successfully implemented. Microbiological tests of aseptic preparation of infusion bags in series by the APOTECAchemo robot revealed an adequate level of sterility and a well-controlled aseptic procedure. The sterility was maintained over extended storage periods, thereby encouraging extended beyond-use dating.

Introduction The management of antineoplastic drugs used for chemotherapy is widely recognized as a high-risk activity. In 2018, our oncology pharmacy implemented workflow improvements to manage the growing workload due to the centralisation of activities from a hospital’s satellite pharmacy, moving towards automated compounding of antineoplastic drugs. The aim of this study was to determine the impact of the centralization on the productivity of the pharmacy department and evaluate the performances of the robotic chemotherapy drugs compounding. Material and methods Data were collected from the hospital information system and the workflow management software, and examined over a 3-year period (2017–2019). The total annual throughput in terms of doses prepared and patients treated and the Medication Turnaround Time (MTAT) were determined. Productivity and dosage accuracy were calculated for the robotic system. Results In 2018, the number of patients treated increased by 16.6%, consequently, the overall number of intravenous preparations compounded in the pharmacy increased by 17.2%. Regarding manual compounding, the total number of antineoplastic preparations decreased by about 2%. Investigational treatments manually compounded increased by about 27%, in contrast to the non-investigational treatments, which decreased by 9.4%. Regarding robotic compounding, the annual production increased by 50.4%. In 2018, the MTAT decreased about 24%. The dosage accuracy and precision of the total amount of doses were -1.1% and 1.2%, respectively. Conclusion This study indicates that in the effort to satisfy an ever-increasing workload, computerization and automation are essential instruments to maintain and ensuring high standards of quality.

AbstractBackgroundRobotic systems are designed to minimize the exposure to antineoplastic drugs during automated preparation. However, contamination cannot be completely excluded. The aim of the study was to evaluate the contamination with antineoplastic drugs on the working surfaces and on the outer surface of the ready-to-use products (infusion bags and syringes) during automated preparation with different versions of a robot and manual preparation.MethodsSurface contamination with platinum (Pt) and 5-fluorouracil (5-FU) was measured by wipe sampling and quantified by voltammetry for Pt and GC-MS for 5-FU. Sampling was performed on pre-defined locations in the working areas before and after preparation of standardized test products. The outer surfaces of Pt- or 5-FU-containing infusion bags and 5-FU-containing syringes were sampled without and after manual capping.ResultsOverall, the surface contamination in the working areas of the robotic system ranged from 0.4 to 114 pg/cm2for Pt and from 1.3 to 1,250,000 pg/cm2for 5-FU. The highest contamination levels were detected after preparation on the gripper of the robotic arm and on the surface beneath the dosing device. In most cases, measured concentrations were higher after preparation. Outer surfaces of infusion bags prepared with the robotic system were less contaminated than manually prepared bags. Contamination on the outer surface of syringes varied depending on the procedure adopted.ConclusionsThe risk of contamination is localised inside the working area of the robot. The outer surfaces of products were only marginally contaminated. Cleaning procedures of the working area are to be further investigated. An effective decontamination procedure for the working area of the robot and automated capping of filled syringes should be developed to further minimize the occupational risk.

Extensive media-fill tests simulating manual and automated preparation of ready-to-use cytotoxic injection solutions revealed the same level of sterility for both procedures. The results of supplemental environmental controls confirmed that the aseptic procedures are well controlled. As there was no difference in the microbial contamination rates of the media preparations depending on the extent of cleaning and disinfection of the robot, the results were used to adapt the respective standard operating procedures.

an extraction of the software was done to study the forced steps (the steps refused by the software but accepted by the pharmacist because of the correct volume read) over a period of 6 months. Results The metrological tests enable to qualify the balances. The bias of the weighing scales fluctuates between 0.94% and 4.40%. Over 6 months, 15 227 preparations were realised with a total of 1 89 334 steps including 49 180 weighing steps. Among those, there were 2023 forced steps (4.1%). The most forced cytotoxic molecules were identified. The two most forced stages were the weighing of the syringe with cytotoxic (41%) and of the final pouch (23%). The 50 ml syringe is responsible for 41% of this forced stage and, in 85% of the cases, it is because the volume to collect has a decimal value. Conclusion Concerning the sensitivity, a method is elaborated to determine the rate of the false negatives with a fake cytotoxic preparations plan and calculated weighing errors. Our method validation plan is complete with the validation of the two components: precision scale and software. REFERENCES AND/OR ACKNOWLEDGEMENTSNo conflict of interest.