Environmental Monitoring for Closed Robotic Workcells Used in Aseptic Processing: Data to Support Advanced Environmental Monitoring Strategies

The human operator is acknowledged as the greatest potential source of contamination in aseptic processing. To avoid contamination, barrier systems have progressively reduced the amount of human intervention in the critical zone. This study extends the trajectory of enhanced patient safety through the elimination of human intervention in aseptic filling. Eight companies that are users of closed robotic workcells have aggregated their usage data from 2018 to 2021. The study analyzes the critical design elements and performance of the Cytiva SA25 Aseptic Filling Workcell. The SA25 is a standardized, fully closed robotic system for aseptic filling of vials, syringes, and cartridges that eliminates operator intervention in the critical zone. The standardized design means that the system is not modified to suit a particular application and the same environmental monitoring strategy can be used across different installations. The SA25 provides significantly increased sterility assurance when producing sterile injectables. Users have observed non-viable particle levels well within ISO 5/Grade A air requirements, with extremely low probabilities of entering a dosage container. There have been zero cases of microbial growth in more than 250 media fills and good manufacturing practice (GMP) batches. Across all dosage formats and sizes, the aseptic process is repeatable, with more than 99.3% of units meeting acceptance criteria. These data demonstrate that eliminating risk through design is successful in the SA25, with an improved aseptic process in comparison to filling systems using Restricted Access Barrier Systems (RABS) or isolators with glove ports. One of the contributing companies to this article achieved an industry first. The U.S. FDA-approved commercial production of their biologic drugs without the requirement for routine viable environmental monitoring (EM), requiring viable EM only during process simulations. Based on the data presented and planned future research, new regulatory consideration should be made for closed robotic workcells to ensure that regulations meant for previous technologies with different risk profiles are not inappropriately applied.