Industry Survey: Best Practices In Container Closure Integrity Testing
Source: Lighthouse Instruments
By Derek Duncan, Ph.D., Director at Lighthouse Instruments
Container closure integrity (CCI) plays an important role in maintaining the sterility and stability of sterile injectable products. New regulatory guidance has recently triggered changes in industry best practices in the area of CCI testing (CCIT). This article summarizes the answers to polling questions that were presented to representatives of pharmaceutical companies involved in CCIT activities. The polls were conducted in the time period March 2019 – March 2020 and the results therefore give a snapshot of industry best practices in this particular time period.
CONTAINER CLOSURE INTEGRITY TEST METHODS
Recent guidance and communications from regulators have made clear that ‘no one test is appropriate for all packages or for all leak testing applications’ (USP <1207, FDA presentations and articles). A current concept that is triggering an evolution in industry CCIT best practices is the implementation of a ‘toolbox’ of CCI test methods optimized and chosen on a per product configuration basis rather than the application of a single legacy test method in a one-size-fits-all approach. The USP <1207> chapter mentions using analytical deterministic methods when possible instead of probabilistic methods such as blue dye and microbial ingress. The first polling question therefore focuses on gaining insight into which CCIT technologies are being implemented to create an appropriate ‘toolbox’ of methods.
SAMPLE SIZE FOR CCI TESTING
Another topic of current discussion is how much CCI testing is required, especially for commercial batches of finished sterile product. Despite the general consensus that CCI is a critical quality parameter for finished sterile product, the industry has historically expended much more effort on testing for particle contamination than for CCI. Visual inspection to detect particulate contamination has been a requirement for many years with 100% inspection of finished parenteral product being done manually or by automated inspection platforms. In the context of risk to the patient, a loss of container closure integrity would, in general, be assessed as being just as critical as particle contamination. The second polling question therefore focuses on understanding industry practices related to 100% CCI inspection.
The results of Question 1 show continued use of the legacy probabilistic methods and initial broad adoption of the deterministic methods. Results of Question 2 show two equal groups looking at 100% inspection versus relying on process control to guarantee CCI quality in manufacturing. Because industry best practices will continue to evolve as the impact of new regulatory guidance becomes clearer, a certain amount of uncertainty in CCIT best practices is to be expected in the near term. However, a general approach that includes the implementation of validated deterministic CCIT methods and the increased generation of science-based CCI data to enable informed risk assessments will help prepare the industry for the future.
