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
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
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.
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).