28/29 April 2021
The USP Chapter <1207> on the integrity testing of primary containers of sterile dosage forms is currently in the second round of review. After a first publication in the UPS-NF Pharmacopeial Forum in September/October 2014 the comments received are now evaluated by the USP Expert Committee. This review process is supposed to be completed in 2015, and it is expected that the new Chapter will become effective in 2016.
Different from the visual inspection, the leak testing of primary containers (so far) has not to be performed to 100% (with the exception of ampoules). Chapter <1207> makes recommendations here, which are - unlike the USP Chapters with numbers less than 1000 - not binding. So the Chapter is rather similar to a guideline than to a pharmacopoeia monograph. For the USP the container / closure integrity is comprised of a package integrity testing and a package leak testing. A simple microbiological challenge test is not considered sufficient. The chapter furthermore lists various test methods, whereby the USP now prefers deterministic methods rather than probabilistic methods. A probabilistic procedure such as the bubble test or the blue bath method can serve well for locating a leak, though. As deterministic methods are listed e.g.: high voltage leak detection (HVLD), laser Headspace analysis as well as the pressure and vacuum decay methods.
For the validation of a method it will be important not only to build on the qualification of the testing device, but to examine the different packaging/product combinations, for example with and without defects.
The revised chapter will be applied to vials, ampoules, syringes and bags. But certain concepts are also supposed to be transferable to active substances, as well as to intermediate or bulk materials in storage.
The current draft of the chapter <1207> can be found in the Pharmacopeial Forum 40(5) - you only need to register, which is free of charge, though.