Microbiological qualification of a robot, Kiro Isolator^® (Grifols), for the preparation of anticancer chemotherapies

Introduction
The preparation of cytotoxic drugs presents a high risk for both patients and healthcare profes-sionals. To handle the increased workload of our production unit while ensuring the quality and safety of preparations, a chemotherapy compounding robot was installed. The Kiro Isolator® is an isolator based robotic system equipped with two arms: one for drug reconstitution and the other for drug withdrawal. This system requires strict aseptic procedures. A gravimetric control is per-formed at each step.

Objective
Microbiological qualification of the robot: verification by aseptic process simulation (media fill test: MFT) that the robot’s preparation process is aseptic.

Materials and Methods
Training on the use of the Kiro robot is provided to operators, covering the three stages of the cycle: pre-treatment (weighing empty containers and connecting tubing), positioning of containers, solvents, and syringes in the robot, and post-treatment (labeling and weighing). The MFT is con-ducted using tryptic soy broth (TSB) as the culture medium. A predefined cycle reproducing criti-cal preparation steps is carried out twice daily over three days by three different operators. Prepa-rations are made from vials of TSB reconstituted by the robot. Each cycle yields: three 50 ml TSB bags with total solvent withdrawal, three 10 ml TSB syringes, and three infusion devices containing 10 ml of glucose and 50 ml of TSB. Final containers, along with a positive control, are stored for seven days at 20 °C, then seven days at 30 °C in an incubator. Daily microbiological sampling is performed on the following areas: handles, work surface, gloves, and air. A visual inspection of the preparations is carried out after 14 days to detect any turbidity. In parallel, a fertility test is performed on a TSB bag to assess the impact of the sterilizing agent on the culture medium. These steps were defined in accordance with Good Manufacturing Practices.

Results
The fertility test was positive if microbial growth was observed. After 14 days of incubation, no mi-crobial growth was observed in any of the 18 bags, 18 syringes, and 18 infusion devices prepared by the robot and operators. Microbiological samples showed no contamination.

Conclusion
Our results demonstrate that the sterilizing agent does not affect the fertility of the culture medium and that the MFT results are conclusive. The microbiological qualification step of the robot is vali-dated, as are all stages of the manufacturing process. The robot can now be used routinely for the preparation of anticancer drugs.

Keywords: robotics, environmental microbiology, essential medicines

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