机器人作为降低制药设施污染的工具

 Image by Tim Sandle.

Robotics is becoming increasingly important in pharmaceutical contamination control, particularly where manufacturing or testing requires very low levels of microbial and particulate contamination. The central advantage is straightforward: robots can remove or reduce the human operator from critical activities. This is significant because personnel are one of the principal sources of microorganisms, particles and fibres within cleanrooms. Internal guidance on advanced robotics similarly identifies reduced human intervention in aseptic manufacture as an important means of lowering contamination risk.

This principle fits particularly well with modern Contamination Control Strategy (CCS) thinking. Rather than relying primarily upon environmental monitoring to detect contamination after it has occurred, facilities should seek to prevent contamination through appropriate engineering and process design. Isolators already contribute to this by providing a physical separation between the operator and critical processing environment. More advanced isolators go further, replacing glove-port manipulations with robotics.

Robotic environmental monitoring

One particularly useful application is the robotic handling of environmental monitoring media within an isolator. Conventionally, placing, exposing, retrieving and manipulating settle plates or other microbiological monitoring devices may require glove manipulations. Every such manipulation introduces some risk through glove contact, disturbance of airflow or accidental interference with critical surfaces.

A robotic system can instead manipulate Petri dishes in a predefined and repeatable manner. For example, a robot could position a settle plate at a defined monitoring location, remove or replace its lid as required by the validated monitoring procedure, and subsequently retrieve the plate for transfer from the isolator. The important contamination-control benefit is not that the robot is intrinsically sterile, but that the operation becomes repeatable and less dependent upon human intervention.

This is particularly attractive in gloveless isolators, where the objective is to eliminate operator intervention in the critical zone. Internal material on modern aseptic filling describes closed, automated isolators without human intervention and specifically identifies robotic systems as technologies that can increase protection from extraneous contamination sources.

Robotics can similarly be applied to vial and syringe handling, component transfer, filling, stoppering, sampling and inspection. The technology therefore supports an important principle of aseptic processing: where an intervention can reasonably be eliminated through engineering, elimination is preferable to attempting repeatedly to control the same manual intervention.

Robots beyond the isolator

Robotics can also help contamination control at room level. Autonomous mobile robots, for example, can undertake selected cleaning or disinfection activities. One technology considered internally is autonomous UV-C disinfection. The information describes robots capable of mapping their environment and performing repeatable UV-C cycles with electronic recording of parameters such as exposure time and distance.

Such systems can reduce the amount of routine manual activity within controlled environments. However, they should be viewed as part of the CCS rather than as replacements for fundamental controls such as appropriate facility design, validated cleaning and disinfection, air filtration, material transfer controls and environmental monitoring.

Qualification and contamination-control considerations

Introducing robots does not automatically remove contamination risk. It changes the nature of the risk. Robotic equipment itself requires suitable hygienic design, cleanroom-compatible materials and surfaces that can be effectively cleaned or decontaminated. Equipment movement must not disrupt critical airflow, generate unacceptable particles or create difficult-to-clean areas.

For aseptic applications, the robotic operation also needs appropriate qualification and validation. Particular attention should be given to:

• reproducibility of movements and positioning;
• impact on first-air protection and airflow patterns;
• cleaning and biodecontamination compatibility;
• particle generation and lubricant containment;
• recovery from robot faults or dropped components;
• interventions required following mechanical failure;
• data integrity and software control; and
• integration into APS/media-fill studies where applicable.

These considerations are especially important because an automated process may operate reliably hundreds of times but still require a human intervention when an abnormal event occurs. Such exceptional interventions should therefore be anticipated and designed into the contamination-control strategy, rather than regarded simply as equipment failures.

Ultimately, the greatest microbiological benefit of robotics is not speed or labour saving. It is the ability to design human intervention out of contamination-sensitive processes. A robot placing Petri dishes inside an isolator is a relatively simple example, but it illustrates a much broader direction for pharmaceutical manufacturing: moving from controlling operator-generated contamination towards removing the opportunity for that contamination to arise in the first place.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)