Container Closure Integrity Testing of Primary Containers for Parenteral Products

Abstract

Container closure integrity (CCI) is the ability of a container closure system—i.e., a package system—to provide containment and protection for the content inside. Ensuring the CCI of a parenteral product package is essential during the entire lifecycle of a product. The chapter first reviews the U.S. FDA regulatory requirements on CCI. Regulations for several regulatory authorities outside the USA are also presented for comparison. From these regulatory requirements, attributes of CCI test are discussed. The chapter is then devoted to two aspects of CCI tests—(1) selection criteria for the test method to use and (2) introduction of six different methods. Selection criteria cover sensitivity and reliability of the method, destructive versus non-destructive methods, inline monitoring versus offline test as well as the material of construction of the primary container. Six methods reviewed are microbial challenge test, liquid tracer leak test, vacuum decay leak test, electrical conductivity leak test, tracer gas leak test, and headspace gas analyzer. Finally, the development, qualification, and validation of a method to be used are discussed. Each CCI test method has its advantages and disadvantages. The selection of an appropriate CCI method depends on the purposes and requirements of the test. In the Summary section, comparisons on the pros and cons for the various methods are presented.