For manufacturers of drug packaging delivery systems — comprising components, vials and single-dose syringes all the way to cutting-edge auto-injector systems — there’s much at stake in the cleanroom environment. The patients who are the ultimate end-users trust their health to the quality, sterility, and integrity of the containers and delivery systems, as well as the accuracy of the measured volume of medication within them.
Cleanrooms play a crucial role in patient safety. Regulators around the globe are moving drug manufacturers toward continuous improvement with zero defects in mind. With injectable drugs, this specifically can mean limiting particulate levels — and the manufacturers of drug delivery systems must do their part to meet this challenge.
It’s important to continually assess new technologies to keep drug packaging and delivery system cleanrooms on the cutting edge. For example, during the manufacturing process, plastic injection molded parts tend to build up static charges, which can potentially attract any particulates that may be present in the cleanroom. Investing in units that help neutralize static charges in the production environment allows airborne particulates to drop to the floor and into the filtration systems.
That’s just a start. It’s essential that packaging manufacturers — especially in healthcare, where so much is at stake with every dose — educate their customers that create the product that will reside in their packaging and delivery systems.
Traditionally, drug manufacturers use glass containment systems for injectables and their cleanrooms are set up for those materials, where static buildup is much less of an issue. Now, with the increasing prevalence of cyclic olefin polymers, which can be more compatible with modern biologic drugs, drug companies need to evolve their processes and implement systems to compensate for potential particulate issues. Sharing this technical information not only helps customers but also the patients who use their products.
Sharing knowledge internally
In the manufacturing industry, it’s common to have cleanrooms in many different locations. Getting everyone on the same page and moving toward continuous improvement takes a formalized process. It can be helpful to have an internal team collect the best ideas from cleanroom teams, distill them into best-practice documents, and share them throughout the company.
It also important to share knowledge of — and experiences with — new technologies. For example, a dynamic particulate-monitoring system tied to a smartphone text-messaging system that alerts cleanroom leaders when particulates are approaching thresholds called “alarm limits,” which means they’re still within appropriate ISO specifications but are trending high. The messaging escalates through floor managers to site leadership the closer particulate levels get to what are considered acceptable limits for the class of cleanroom. Cleanroom operators can employ several standards, including ISO 7 (Class 10,000), ISO 6 (Class 1,000), and ISO 5 (Class 100), depending on what manufacturing processes are deployed in a particular room.
Many cleanroom operators use static systems such as manual interval checks of temperature or humidity levels. By employing real-time, dynamic monitoring through sensors tied to alert messaging, operators can receive updates on temperature, humidity, and particulate levels every few seconds, along with pressure readings from inside the room to the gowning area, and from the gowning area to the outside, to ensure the gradients between the three areas are correct.
Getting to the root cause
Measuring particulates and automating the alerts isn’t enough, on their own, to effect continuous improvement. It’s important to constantly question why something is happening and look at the manufacturing processes that might be causing it.
An example involves the purging process for injection molding machines: before a run of a particular part or product, any remaining material from the last run has to be removed from the machines. Of course, this emits particulates into the air, which would be undetectable unless you were running monitoring at that moment.
Looking toward the future
In the constant quest for zero defects, there is a next frontier: sub-visible particulates. While experts argue whether a “visible” particulate is 50 or 125 microns wide, the fact remains that today’s technologies detect particulates in that range, much like the human eye.
In the last decade, particulate detection and automation has improved exponentially. It is still important, however, to have teams continually researching new technologies and equipment to mitigate sub-visible particulates and find ideas for making drug packaging and delivery system cleanrooms even cleaner.
The other frontier is automation. Anyone charged with a cleanroom knows that entering and exiting the space can present risk of contamination. Working toward more automation could help to address this. However, it is an evolving process, as technology marches on and each year brings new automation tools.
But right now, there’s another way to reduce the amount of people coming and going from a cleanroom: by increasing visibility from the outside. For example, by installing longer viewing corridors as well as strategically positioned camera systems, facility managers may provide the view needed to answer a question that formerly required entering the cleanroom.
Some of the practices to continuously improve drug packaging and delivery system cleanrooms are giant leaps, while others may at the time seem incremental. When you work in healthcare manufacturing, though, every avenue and side street is worth exploring. Everyone in the supply chain contributes to products that ultimately affect patients’ health — an extraordinary task that requires continual improvement.
Tom McLean is Vice President, Delivery Systems R&D, of West Pharmaceutical Services Inc., having joined the Tech Group in 1999 as a Program Manager responsible for Consumer Product Development. Tom has earned Six Sigma Master Black Belt certification, and led the transition of West’s Scottsdale, Ariz. facility to develop and commercialize West Delivery System medical device products. He now leads the Delivery System R&D Organization, whose main responsibility includes the development of delivery system products from concept through product design verification and validation. www.westpharma.com