A Multicompany Survey Study for Helium Leak Container Closure Integrity Test.

All products labeled as sterile are required to be free of microbial contamination throughout their shelf life (obligatory CQA). Container Closure Integrity (CCI) needs to be addressed with a holistic lifecycle strategy comprising adequate primary packaging components selection and the assessment of critical unit operations and Critical process parameters (CPPs) according to quality by design (QbD) principals. The Helium leak method is currently the most sensitive CCI test method and preferably used for the initial container closure system (CCS) qualification and characterization studies. Currently, two different measuring principals are used in the pharmaceutical industry and no data is available in the public domain for typical method performance parameters such as accuracy, precision, intermediate-precision, and limit of quantification of the method. Furthermore, the performance of different types and sizes of artificial leaks as well as certified helium leak standards has not yet been characterized across different test laboratories. In this intercompany study, we prepared 17 artificially prepared leak samples using the most common types of artificial leaks in relevant nominal size ranges which are commercially available or can be easily prepared in a laboratory. Each participating lab did generate results according to their in-house methods applying their established test parameters as the aim of the round robin study was not to create a standard for Helium leak measurements, but to compare real world performance between different laboratories.