The Impact of Automation on Aseptic Processing - Pharmaceutical Technology

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The Impact of Automation on Aseptic Processing
The authors review the role of automation in aseptic processing and describe their experience in implementing advanced technologies, including the use of isolators and robotics.


Pharmaceutical Technology


After a few years, a new vial line was installed that for the first time introduced automatic vial washing, continuous dry-heat tunnel for sterilization, and depyrogenation of glass vials. This far more advanced processing line operated at up to 300 vials/min and required only two operators, while the older vial lines it replaced required as many as six people working constantly. This processing line also featured far better stopper feeding and needed far fewer line interventions. The results were dramatic. As a result of the higher speed, media-fill tests expanded in sample size to 5000 units or more, and zero contamination results became far more common (2). In addition, although the cleanroom design and gowning conditions remained unchanged, environmental monitoring results were quite obviously improved in every facet. This fact was attributed to the lower personnel population in the filling room and the less vigorous work required because vial supply, previously a laborious task, had been fully automated.

Not long after the introduction of this improved and more automated vial line, a continuous ampul line was introduced and the improved performance was even more striking. Because of the very high speed operation and changing regulatory requirements, management made the decision to conduct media fills that lasted one full hour. As a result, media-fill sample size increased to approximately 25,000 units. Only one operator was required to run the line, and by and large they were only required to observe the line and to correct infrequent jams. An important lesson was learned and a lasting impression was made: Automation and the elimination of interventions reduced risk, not just theoretically but in practice as the results emphatically demonstrated (3, 4).

During the late 1980s, Shibuya Kogyo (Kanazawa, Japan) was selected to design, build, and install a state-of-the-art vial processing line at E.R. Squibb (New Brunswick, NJ). This vial production line embodied what were a number of automated features that are now rather common but were quite unusual two decades ago. One of us (Izumi) was directly involved in this project and the other (Akers) was fortunate enough to visit the facility not long after validation was completed and eventually became a technical consultant to Shibuya Kogyo. This facility not only had a fully automated vial-washing and depyrogenation system but also included automated weight checking, vial-handling advancements designed to prevent misfeeds, automated clean-in-place and steam-in-place systems to eliminate aseptic connections in set-up, and automated lyophilizer loading of three large production lyophilizers. Although the data processing and acquisition systems available at that time were far less sophisticated than what is available today, this filling line was arguably the most sophisticated aseptic production line in use in the pharmaceutical industry at the time of its installation. Automation had eliminated even the highly risk intensive aseptic set-up and lyophilization loading activities.

The ability of this system to run with minimal line stoppages and infrequent interventions pointed the way to the future in another way. It seemed that a marriage of automation and isolator technology, which was also an emerging and exciting new concept in pharmaceutical aseptic processing, would be a logical way forward. This has proved to be the case and the remainder of this article will be devoted to an overview of a few projects undertaken over the past decade and a half and will explain the role played by automation in solving sometimes difficult production challenges.

Modern automation

Webster's Unabridged Dictionary defines automation as "The technique, method, or system of operating or controlling a process by highly automatic means, as by electronic devices, reducing human intervention to a minimum." This is obviously and appropriately a very broad definition that includes what might be called machine automation as well as the field of robotics. Over the years, we have been involved in several projects that use automation and robotics, usually within the same process with the objective of as Webster's says, "reducing human intervention to a minimum." However, the objectives in these pharmaceutical manufacturing projects are not merely to relieve human operators of repetitive and often boring tasks undertaken in difficult or uncomfortable environments but also to reduce end user or patient risk from contamination. Experience has shown that automation and robotics can achieve both of these goals. In cases of high pharmacological activity and allergenic, cytotoxic, and radiological products, the benefit of increased operator safety also can be added (5).


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