08.03.20 -- Container Closure Integrity And Deep Cold Storage: What You Need To Know

Studies have shown that deep cold storage temperatures can introduce risk to the container closure integrity (CCI) of vial-rubber stopper combinations traditionally used to fill sterile pharmaceutical products. The material properties of the primary packaging components at these low temperatures can sometimes result in gaps appearing at the sealing surfaces.

If container closure integrity (CCI) is lost during -80°C storage, nonsterile, cold, dense gas from the storage environment (i.e., air from a -80°C freezer or carbon dioxide from dry ice) can leak into the stored vial. It is therefore critical that robust development work is done to understand the CCI performance of any primary packaging components used for product needing deep cold storage and transport temperatures.

Studies have shown that robust and consistent vial sealing is critical for maintaining container closure integrity (CCI) at deep cold storage temperatures. A test to assess how well a vial is sealed is the measurement of the residual seal force (RSF) of the compressed rubber stopper (USP<1207.3). RSF testing provides a way to quantitatively optimize and qualify the vial sealing process.

A gene therapy clinical trial was halted due to container closure integrity (CCI) issues in deep cold storage. A CCI test method was developed that enabled nondestructive CCI testing of product vials at these cold temperatures. The capability to nondestructively test clinical product in deep cold storage enabled troubleshooting studies leading to corrective actions that assured good CCI.

When working on live viral vaccines, gene therapies, or product that contains active cells, cold storage is often required to maintain stability and/or activity. Deep cold storage, at dry ice (-80°C) or even cryogenic (-196 °C) temperatures, poses a significant challenge to packaging components and can result in container closure integrity (CCI) failures. Watch this webinar for a detailed presentation on this topic.

It is essential to generate robust data that demonstrates the maintenance of seal integrity during deep cold storage and/or transport which, in turn, requires a robust container closure integrity (CCI) test method. This article describes the development of such a test method for vials stored at -80°C.