Robotic sampling can be applied to the surface sampling of isolators, restricted access barrier systems (RABS), and other critical environments where sampling by human operators results in a potentially risky intervention near sterile surfaces and components or is ergonomically difficult to achieve. Although this robotic environmental monitoring system has previously been reported upon in several public lectures, this article for the first time provides data regarding the performance of this system in surface sampling (1). This automated approach to environmental monitoring—aimed at reducing interventions—was developed in response to the US Food and Drug Administration's 2004 Guideline on Sterile Drug Products Produced by Aseptic Processing as well as the agency's report on Pharmaceutical CGMPs for the 21st Century: A Risk-Based Approach. The ultimate objective is to eliminate human interventions in critical aseptic space and to collect process control data in real time as much as current technology allows (2). This article presents a study of an aseptic environmental monitoring system for surface contamination at critical areas using a robot that can be programmed according to predetermined sampling parameters.
The robotic system described conducts active-air and settle-plate monitoring as well as surface monitoring using swabs. However, this article reports only on studies done on the surface-sampling capabilities of this robotic system. It is anticipated that in production operations, this system would handle surface and air sampling and that nonviable or total particulate sampling would be automated as well, using currently available technology. The authors hypothesized that a robot that can be programmed in terms of pressure applied to a swab, and also can be programmed to sample a given surface in a highly reproducible manner in terms of area sampled, might actually yield better recovery than a human sampler.
In the near future, an automatic environmental monitoring system could also include rapid microbiological methods, which would allow the direct, and nearly real-time enumeration of contamination. The authors understand, however, that because those technologies would enumerate cells rather than colony forming units (CFU), some reconsideration of monitoring levels or contamination incidence rates would be required.
Isolators were introduced for aseptic processing in the 1980s, and for the most part, conducting environmental monitoring has been logistically difficult. In some projects, microbiological monitoring could not be easily accommodated, and modifications to the system's design were required after the fact. At present, the reliability of gloves and half-suits is widely considered a weak point in isolator or RABS operations. The authors believe that the automation of environmental monitoring to avoid direct human intervention will be a requirement in the evolution of gloveless aseptic processing systems. In addition, the automation of environmental monitoring and consideration of locations and sampling points during the construction of the filling system will obviate planning and logistics issues concerning environment monitoring (3,4).
A corollary benefit of an automated approach to microbiological monitoring will be near elimination of false positives (2). The system reported in this article requires no manipulation by human operators either in preparing samples or in handling them. Also, because the sampling materials can be identified automatically by barcode, the control system can correlate the sample identification with location and time that are then stored electronically (1). All sample materials are vapor-phase-hydrogen-peroxide-decontaminated before use.