Container Closure Integrity

In 2011, the US FDA issued an advisory regarding the potential formation of glass lamellae in vials containing injectable drugs. This was in response to several drug recalls in 2010-11. The number of glass-related drug recalls has since declined greatly. This no doubt is due to key actions taken by pharmaceutical manufacturers before the drug goes to market, even during the development phases.

Container closure integrity (CCI) is a critical factor every drug manufacturer and compounder is required to achieve. To achieve CCI, one must consider factors such as vial material, blowback, and stopper design. One vital factor – too often an afterthought – is the aluminum seal.

West’s Integrated Solutions program brings together all West’s products/services and industry knowledge into customer-focused solutions that Simplify the Journey™. One aspect of Integrated Solutions is wide-ranging analytical services, which includes state-of-the-art container closure integrity (CCI) capabilities. Understanding CCI as it relates to industry expectations, manufacturing, and regulations can be a challenge.

With the advancement of high-value biologic, gene, and cell therapy drugs, there is a growing interest in assessment of container closure systems (CCS) at the low temperatures experienced during processing, storage, and shipment. A vial-based CCS is usually capped at room temperature, but thereafter it may be exposed to low temperature conditions (0^oC to -180^oC), depending on both the drug characteristics and the expected duration of storage.

Parenteral drug products must be stored in a container system that provides good container closure integrity (CCI) over shelf life for the purpose of preventing environmental contamination. This system typically comprises a glass vial, elastomer stopper, and an aluminum seal. USP Chapter <1207> Packaging Integrity Evaluation – Sterile Products discusses in detail methods to measure CCI to determine if the system can meet the maximum allowable leak limit (MALL) for its specific drug product (i.e., the smallest gap, or leak rate, that places quality at risk). Critical to achieving good CCI is proper capping of the vial with the stopper and seal, making sure that the compression level of the stopper is appropriate.

Many complex biologic drug products, such as gene and cell therapies, require storage at low temperatures (from -60oC to -180oC). This presents a challenge for containment systems when maintaining container closure integrity (CCI) – especially for glass-rubber vial systems.