Birgit Mueller-Chorus Ph.D.
Manager, TCS. Components Development
April 27, 2021
CCIT uncovers issues that can result in loss of sterility, such as improper component fit, improper assembly, cracks, scratches, or fibers/particles. Smaller issues may allow only gas ingress, where larger issues may allow liquid or microbial ingress. A key concept in CCIT is the "maximum allowable leakage limit" (MALL). This was introduced in United States Pharmacopeial Convention (USP) Chapter <1207> Sterile Product – Package Integrity Evaluation. MALL is the greatest leakage rate that can be accepted for a given drug package system. It is unique to each drug package system and should form the basis of CCIT.
Many methods are available to perform CCIT. USP <1207> provides an overview and categorizes them as “deterministic” or “probabilistic”. A “deterministic method” directly and quantitatively measures a physicochemical property that generates the potential for leakage. An example is tracer gas leak detection with helium. Deterministic methods can be used to generate science-based data throughout the product life cycle to develop a package integrity profile that can be used as input for risk management. A “probabilistic method” is based on an event having a probability of occurring, and thus is less precise. USP <1207> endorses deterministic methods as preferred, but does support probabilistic methods when no deterministic method is available.
West's Analytical Lab Services has the capability to perform the full range of CCIT – deterministic and probabilistic. For more on how West can advise and support CCIT, contact a Technical Customer Support (TCS) representative or Account Manager.