Gloveless isolator? No, its a closed robotic workcell
Is “gloveless isolator” the best term to describe a fully closed system for aseptic filling?
Jim Akers, an expert in aseptic processing, posed this question in a recent article in the PDA Letter titled “Gloveless isolators offer speedy throughput.”
You can download the article below.
Akers neatly summarizes his argument in this section:
“The challenge is operating an aseptic processing activity without human intervention….Gloveless isolators are an effect of outstanding automated process engineering—not the cause. Manufacturing requirements and the existence of reliable automation have made it feasible to eliminate interventions. Taking a glove off an isolator without eligible full automation is like taking the training wheels off a child’s bicycle before the child gains the ability to ride unassisted.”
The article sparked a conversation at the Vanrx User Group meeting, an annual event where Vanrx customers gather to collaborate on operational and regulatory questions.
Participants agreed that “gloveless” as an isolated term was meaningless. Words including “robotic”, “fully closed”, “standalone”, “automated”, “workcell” and “integrated” were used frequently during the discussion.
What is the right term for this new type of filling machine?
We think the best term is closed robotic workcell.
Let’s break that phrase down piece by piece.
Closed is used in a literal sense, where the system remains completely closed while in operation.
It is possible for the system to be completely closed because the sources of interventions have been designed out of the aseptic process. Containers or closures are always handled in nests, never individually. There is never any container breakage, tipping or machine jams. Closures also are handled in nests, and all units in a nest are closed simultaneously. There are no glove ports, mouse holes or any other points of ingress /egress on the system, so the system is completely closed.
Crucially, humans are removed from the process. The system relies on the operator having a clear understanding of the automation system to operate the system, but it is not expected that the operator would have to manually intervene for any reason.
Robotic refers to the role of robotics in performing all of the material handling, filling and closing activities. This differs from conventional filling technologies, where electro-mechanical parts perform the same function. The need for interventions arises from the use of such parts, so they must be designed out in order to close the isolator.
Robots are employed because of the very high repeatability they provide, performing the same actions for long durations with accuracy to the tenth of a millimetre. These are specially designed robots in the sense that they minimize particle generation and can withstand cleaning and decontamination substances; something Vanrx has termed “isolated robotics.”
Workcell is borrowed from the semiconductor industry, and describes a standard system performing a discrete action within an overall process. In this case, that’s filling and closing vials, syringes and cartridges. Each Workcell is like every other. Standardization provides two benefits: it makes the systems faster to build and allows fleet-level improvements to their performance and reliability.
Workcell also differentiates against systems that might be closed and robotic, but are customized or modular and cannot benefit as readily from future improvements in both hardware and software design.
Taken all together, these are closed systems that can aseptically process dosages with no human input in the operation.
Effective process automation is the difference maker between closed robotic workcells and competing systems that incorporate robots for some operations. As Akers says, system design arrives at this point by deeply understanding what needs to be automated and designing a fully integrated, effective process to do it. Only then can the system be closed, creating the best possible outcome for drug product quality and managing risk.
Closed robotic workcells and sterility assurance
The discussion above flirts with the topic of sterility assurance, so let us address it head-on. Akers concludes that “…eliminating the human element requires a complete rethinking of process control. The much relied upon method of environmental monitoring becomes far less important as contamination sources are eliminated.”
In conventional filling systems, where containers and closures move through conveyors and star wheels, and stoppers are in sortation bowls, extremely detailed environmental monitoring makes sense. Your risk of contamination is throughout the inside of the barrier system, including every product contact surface.
In a closed robotic workcell, the hazard contact pathway for the drug product is through a single-use, pre-sterilized flow path and into the container. Environmental monitoring requirements are different, because much of the risk has been removed. Containers and closures are not making contact with multiple surfaces. Airflow and monitoring are closely linked at the point where the container is filled to remove risk.
Plus, since the system is completely closed, it can run cleaner than the ISO5 / Grade A required as a standard. Workcells also use only press-fit closures with integrated stoppers, which increases product quality by eliminating the risk of particle introduction or incomplete crimps of aluminum caps.
Summarizing this topic, closed robotic workcells make significant improvements to sterility assurance and drug product quality by eliminating sources of risk. Simultaneously, active EM is in place to understand and control the process within the workcell.