Fully automated production is fast becoming the standard for the biopharmaceutical manufacturing industry. At the same time, many fill and finish businesses are still struggling with a consistent source of variability in their automated production processes: inconsistently double-bagged tubs of pre-sterilized syringes.
Variation in tub packaging continues to create financial and operational challenges for the entire downstream supply chain. It’s time for our industry to align on packaging configuration requirements that make tubs fully processable on automated lines.
Increasing demand for pre-sterilized formats and quality requirements
When pre-sterilized systems were introduced in the early 1980`s, they were intended primarily for labs and small filling. They were packaged in a bag that simply had to keep its contents clean and sterile until it was opened. Unbagging a tub of syringes was a manual process with little impact on the small-scale use cases of the time.
But much has changed in forty years. Today, pre-sterilized syringes are the requested industry standard for filling of prefilled syringes, which now make up a significant portion of the pharmaceutical injectables business. With the growing demand for these products, the aseptic production processes as well as quality and regulatory requirements have also changed.
Pharmaceutical fill finish companies now increasingly rely on high-speed syringe filling machines. This machinery can have a nominal output of >50,000 units per hour, or about six tubs of syringes every minute.
Production volumes this large have only been made possible by automating as many production steps as possible, including the process of unbagging tubs. Like any mechanized manufacturing system, today’s advanced filling lines depend on reproducible characteristics and precision, in both the filling steps they perform and the components they process. Variability of any kind can create significant challenges – and double-bagged nested syringes are one of the troublesome culprits.
Aseptic quality requirements are tightening, especially with new Annex 1 contamination regulations on the way. Double-bagging syringe tubs is a valuable sterility solution for these businesses, especially for those who aren’t using E-Beam sterilization equipment to sanitize the outside of the bag before a tub is introduced to a higher-level cleanroom.
For drug manufacturers who don’t rely on this equipment, double-bagged tubs help enable compliance with aseptic quality requirements. As tubs move along the filling process, one bag can be removed each time the tub enters a higher cleanroom level.
The double bagging process: Source of variability
The production challenges begin well upstream from the automated production lines, starting with the way primary containers are packaged by their manufacturers.
Nested, ready-to-use syringes are typically packaged in tubs that are sealed with a gas permeable foil, then bagged. Downstream production challenges often originate with the bagging process, which is still a manual one for most syringe suppliers. The process usually involves several steps:
- An operator places the tub in an inner bag, which is then sealed
- Since the inner bag is typically the same size as the outer bag, the sealed flaps of the inner bag are then folded up and fixed in position while the operator inserts the tub into the outer bag
- The outer bag is then also sealed for delivery
Unfortunately, this manual approach inevitably leaves these processes susceptible to inconsistency in the bagging results
This lack of packaging standardization can be challenging for automated processing facilities, which depend on the repeat precision of every input to deliver the rigorous efficiency and distinctive quality that our industry now expects.
For drug manufacturers who use mass volumes of pre-sterilized syringes, the biggest problem often begins when the outer bag is opened – the moment when challenges unfold along with the inconsistently packaged inner bag.
The automated unbagging process at the filling site
In theory, this ought to be a straightforward process. Here’s how it’s typically designed to work:
- First, the outer bag is cut open and transferred.
- The tub with the remaining inner bag is pushed through an opening (“mouse hole”) into the cleanroom area.
- At this point, the folded inner bag should relax and unfurl before the tub reaches the cutting station at the mouse hole entry to the Class A cleanroom area. While most inner bags partially unfold due to restoring forces, process aids like mechanical guides and compressed air nozzles can help further unfold the bag to a flat flap that can be readily opened by a cutting device.
In reality the results are often far less satisfactory. So where do the issues arise? In a nutshell, it is the incompatibility between the alignment of manual and automated process.
Manual bagging: A challenge for automation
Most suppliers for primary packaging container continue to manually bag their tubs according to their own internal packaging specifications. This approach relies heavily on operating instructions and the frequency and quality of operator training to enable consistent outputs. The predictable result: considerable variability in the tub packaging, especially in the position and folding of the inner bag.