Closed Container Integrity Testing Equipment in Compliance with EU Annex 1

How does Bonfiglioli Engineering’s (BE) testing equipment provide companies to comply with the new EU Annex 1 packaging guidelines for closed container integrity (CCI)

BE was founded 50 years ago making it one of the world’s most experienced container test companies. Let’s look at each of the five points in Annex 1 that cover CCI and connect them to the BE systems that will address them.

1) Annex 1, 8.21 - Final containers should be closed by appropriately validated methods.

BE’s main offers include both off-line for lab testing and 100% leak testing systems for vacuum decay leak testing (VDT), pressure decay leak testing (PDT), or headspace gas analysis (HGA) for a wide variety of rigid and flexible pharmaceutical container which comply with ASTM methods, Annex 1 guidelines, and UPS’ preferred deterministic test methods. With over 50 years of experience in CCI testing, Bonfiglioli has thousands of validated systems in operation around the world.

For off-line testing:

· The LT Pro is BE’s benchtop lab system for either VDT or PDT testing of containers

· The Laser Pro is BE’s benchtop HGA for containers.

Both systems offer highly sensitive, very accurate quantitative test results. VDT and HGC are completely non-destructive, and PDT is non-destructive for non-leaking samples.

For testing 100% of your production:

· BE’s PK series of machines offer vacuum decay or pressure decay leak testing for many different types of containers including vials, syringes, cartridges, BFS, IV bags, and pouches.

· The LVA600 allows for 100% laser-based gas headspace analysis typically used for lyophilized vials to check the internal pressure in the container; or in any case where you need to check a nitrogen headspace layer is being maintained in a container and to know that oxygen if oxygen ingress is occurring.

In addition, BE offers semi-automatic machines for those cases where you have smaller production runs/batches. A benchtop system may be too slow, and a fully automatic system is “too much” system to use for those smaller batch sizes.

2) Annex 1, 8.22 - Where final containers are closed by fusion, e.g. Blow-Fill-Seal (BFS), Form-Fill-Seal (FFS), Small and Large Volume Parenteral (SVP & LVP) bags, glass or plastic ampoules, the critical parameters and variables that affect seal integrity should be evaluated, determined, effectively controlled and monitored during operations. Glass ampoules, BFS units and small-volume containers (≤100 ml) closed by fusion should be subject to 100% integrity testing using validated methods. For large-volume containers (>100 ml) closed by fusion, reduced sampling may be acceptable where scientifically justified and based on data demonstrating the consistency of the existing process, and a high level of process control. It should be noted that visual inspection is not considered an acceptable integrity test method.

· The PK-VS is an excellent system for 100% inspection of BFS containers, either single ampoules, ampoule strips, or other BFS container shape

·?The PK-VF is the answer for how to inspect 100% SVP bags such as IV bags ≤100 ml

This system answers the challenge of how to comply with the new Annex 1 requirements r for 100% CCI for smaller fusion-sealed containers.

3) Annex 1, 8.23 - Samples of products using systems other than fusion should be taken and checked for integrity using validated methods. The frequency of testing should be based on the knowledge and experience of the container and closure systems being used. A scientifically justified sampling plan should be used. The sample size should be based on information such as supplier management, packaging component specifications, and process knowledge.

· BE’s benchtop and semi-automatic CCI testing systems will be great choices to handle SPC container testing, while, if desired 100% testing can be performed on non-fusion seal containers as well. The LT Pro and Laser Pro systems are directly scalable to BE’s 100% inspection systems. In other words, the technologies and test methodologies for the benchtop units match those on the 100% online systems.

4) Annex 1, 8.24 - Containers sealed under vacuum should be tested for maintenance of vacuum after an appropriate pre-determined period prior to certification/release and during shelf life.

· BE can offer the Laser Pro system for SPC testing or the LVA600 for 100% testing to check the vacuum level.

· In some cases, VDT can be used to check to see if a vacuum has been lost as normally a sealed container filled with vacuum does not affect the VDT systems transducers, while in a container where the vacuum was not properly maintained, the VDT systems transducers will detect gas coming from the container. It is important not to test at a vacuum level below the expected normal vacuum level in a non-leaking (known good) container.

5) Annex 1, 8.25 - The container closure integrity validation should take into consideration any transportation or shipping requirements that may negatively impact the integrity of the container (e.g. by decompression or extreme temperatures).

· BE’s HGA systems will be able to detect any changes in either the oxygen lever or pressure (moisture) level in a container with headspace and BE’s VDT or PDT systems can be used on containers without headspace to check if a container is leaking by determining a leak rate from the container that corresponds to a micron hole size.

Besides all the systems mentioned above, BE offers multiple combination systems to include different testing methodologies on one space-saving platform:

· Automated Visual Inspection (AVI) and VDT or PDT

· AVI and HGA

· AVI and VDT or PDT, plus HGA

Want to learn more about our equipment and how we can help you elevate the quality of your processes? Send an email to [email protected] to get in touch with our team of experts.