Manufacturers typically use syringes or other types of medical devices to hold pharmaceutical drugs or biologics. If the drug or biologic claims to be sterile, each batch or lot needs to be tested to ensure the product conforms to sterility requirements.
A product labeled as sterile is expected to be free from viable microbial contamination throughout its entire shelf life. Sterility tests will only detect viable microorganisms present at the time of the test. These microorganisms can only be detected if they are capable of growth in the culture media. Potential interference can be introduced at the time of testing, which could produce false positive readings. Sterility tests are always destructive of the samples and do not have the opportunity to reexamine the same sample in the event of positive or negative results.
Container closure integrity testing (CCIT) offers a viable alternative to sterility testing. Container closure integrity (CCI) is defined as the ability of a container closure system to provide protection, and therefore maintain the efficacy and sterility of a product throughout its shelf life. The ability of elastomer components to prevent microbial ingress into containers is determined through CCIT, which measures the integrity of the seal between the closure and container.
Recently, the United States Pharmacopeia Convention (USP) published a guidance document that addresses test methods in detail for primary containers of sterile dose forms: Chapter <1207> Package Integrity Evaluation – Sterile Products.
USP Chapter <1207> recommends the use of deterministic methods against probalisitc methods whenever possible. A deterministic test method (e.g., tracer gas leak detection, high-voltage leak detection, laser-based headspace analysis) is one in which the leakage being measured is based on physiochemical technologies that are readily controlled and monitored, yielding objective quantitative data. A probabilistic leak test method (e.g., Dye ingress, microbial ingress) is the converse of a deterministic leak method, being stochastic in nature and relying on a series of events resulting in random outcomes.
Choosing a CCI method depends upon the container system being evaluated; suitability of a single method throughout the life cycle of a product may differ. The experts at the Cryopak Testing Center (CTC) can assist you in determining the right test method for your system. Please contact CTC for further consultation or for a quote.