According to EU GMP Annex 1, containers closed by fusion, should be subject to 100% integrity testing. Various non-destructive methods are available, but only a few are deterministic and ensure reliable results as well as minimal false reject. The second aspect is gaining significance since the traditional sodium IV bag product margin is low and high false reject rates are disastrous and a huge business risk.

The IV bags are traditionally tested just prior to the secondary packaging phase. In case of post sterilization (non-aseptically filled bags), the FMEA requires the inspection to take place after sterilizing. Ultimately, the sterilization process (e.g. steam sterilization) introduces risk to the CCIT system by means of water droplets on surfaces or water trapped in crimps, temperature variations and unsteady room humidity.

• Manual visual inspection for leaks is labor intense and not data driven.
• Vacuum Decay test methods lead to high false reject rates due to environmental influence (humidity and temperature).
• Flexible containers are difficult to handle for automated processes, especially large and wobbly bags.

Our customer approached us for a development of a fully automated 100% inline leak detection platform after steam sterilization. The force squeezer (FS) method had proven to be unaffected by residual humidity on the bag surface or by trapped water under the aluminum crimp. By means of a force measuring system the differential force of bags was measured while being squeezed.

This FS test method safely identifies small leaks in the headspace area and large leaks in the liquid filled area.

During a risk analysis, the port area of the IV bag was found to be the most risky area to identify a leak, while the bag body with a pinhole in the foil was the least risky.

• Force Squeezing technology measures the loss of resistant force on a flexible container when mechanically squeezed. The force on the load cell is monitored within a certain testing time.  The compression cycle commences with the initial sensing of the load and terminates with last sensing of the load. Large leaks as well as small leaks are detected accurately.
• The engineering and method development studies resulted in an automated inspection machine that holds the IV bag in a vertical orientation with the port to the top. This allows a high sensitive FS measurement in the headspace.

• A robot material handling solution was chosen for the fully automated loading of the vertical FS test stations.
• Liquid-filled bags are not easy to handle for robots, especially when dealing with different sizes and when bags are delivered at different intervals from a conveyor belt - sometimes crooked and wet from the upstream steam sterilization process.
• In this particular case, eight robots are working simultaneously to accomplish the high throughput (> 15’000 bag / h with bags sized up to 1’000 ml).
• At the factory acceptance test in Wohlen our customer was totally convinced of the effectiveness of this machine.  The required reliability of bag testing, loading and unloading of 99.5% was far exceeded.