OLVG, Department of Clinical Pharmacy, Amsterdam, the Netherlands.
Loccioni, Moie di Maiolati (Ancona), Italy.
Eur J Pharm Sci. 2019 Mar 15;130:181-185. doi: 10.1016/j.ejps.2019.01.034. Epub 2019 Jan 31.
Compounding of cytostatic drugs requires strict aseptic procedures, while exposure to toxic drugs and repetitive manual movements should be minimized. Furthermore, reuse of vials is desirable to lower the costs. To assess if all this might be safely achieved with a robot, this study aimed at qualifying the aseptic preparation process with the robotic system APOTECAchemo.
The aseptic compounding of patient-individual cytostatic solutions was simulated with media fill simulation tests to qualify the performance according to European GMP Annex 1. The contamination in the environment was measured in critical places using settle plates, contact plates, active air sampling and particle counting. Media-fill simulation tests were prepared in 3 production batches. The second part of the study evaluated the microbiological shelf-life of commercial drug vials after repeated puncturing. On six days, fifty syringes of 15 ml media were prepared from the same 50 vials with the robot. After each preparation, vials were covered with an IVA seal upon unloading from the robot to protect them from microbiological contamination.
No microbiological contamination was found in any of the 96 media fill preparations, nor in any of the 300 syringes that were prepared with repeated puncturing. The compounding area met class A limits, while class A criteria were not fulfilled by the contact plates and settle plates placed on the right side of the loading area. There, the average colony forming units (cfu) were 3 and 1.17, respectively, meeting class B criteria.
Robotical compounding of cytostatic drugs with APOTECAchemo meets the microbiological requirements of the European GMP. In addition, the robot can reuse vials repeatedly and safely, thereby enabling extended usage.
细胞毒性药物的配制需要严格的无菌程序，同时应尽量减少接触毒性药物和重复的手动操作。此外，重复使用小瓶以降低成本也是可取的。为了评估机器人是否可以安全地实现所有这些目标，本研究旨在对 APOTECAchemo 机器人系统的无菌制备过程进行质量确认。
通过介质填充模拟测试模拟患者个体化细胞毒性溶液的无菌配制，以根据欧洲 GMP 附录 1 对性能进行质量确认。在关键位置使用沉降板、接触板、主动空气采样和颗粒计数来测量环境中的污染。准备了 3 批生产批次的介质填充模拟测试。研究的第二部分评估了商业药物小瓶在重复穿刺后的微生物货架期。在六天的时间里，用机器人从 50 个小瓶中准备了 50 个 15ml 的介质注射器。每次准备后，从小瓶中卸出小瓶后，用 IVA 密封将其覆盖，以防止其受到微生物污染。
在 96 次介质填充制备中，在 300 个通过重复穿刺制备的注射器中均未发现微生物污染。配制区域符合 A 级标准，而放置在装载区域右侧的接触板和沉降板不符合 A 级标准。在那里，平均菌落形成单位（cfu）分别为 3 和 1.17，符合 B 级标准。
APOTECAchemo 机器人细胞毒性药物的配制符合欧洲 GMP 的微生物要求。此外，机器人可以安全地重复使用小瓶，从而实现更长的使用时间。
