Container Closure Integrity

When selecting the appropriate rubber stopper for any respective vial containment system, there are many aspects to consider regarding the properties of the elastomeric closure. For the purposes of this discussion, the focus will be on the functional performance of the stopper and what key aspects should be considered during the assessment and selection process. Coring and fragmentation, container closure integrity, and machinability of the stoppers will be briefly reviewed.

The FDA has approved over twenty (20) cell and gene therapy drugs, and with the rapid growth of the cell and gene therapy market, there is greater demand than ever to demonstrate container-closure integrity (CCI) at ultra-low temperatures. To preserve the product’s efficacy, most cell and gene therapy drugs are stored at temperatures below -60ºC. Many of these products are packaged in either vial systems or cryogenic freezing bags. While each of these container-closure systems poses a unique challenge for the evaluation of CCI at ultra-low temperatures, the discussion in this blog focuses specifically on vial systems.

Container closure integrity (CCI) has been a fundamental core requirement of containment and delivery solutions in the West product portfolio. Container closure systems (CCSs) must maintain both the sterility and stability of pharmaceutical products; very importantly they must be free of microbial contamination. Microbial ingress into a CCS will jeopardize product sterility.

Moisture-sensitive drug products are commonly lyophilized to enhance their shelf life and to prepare them for storage and transport. Maintaining a constant moisture level in a lyophilized drug product “cake” ensures product quality. Not only is proper selection of a container closure system (vial, stopper, seal) necessary, but sealing conditions are as well. This is achieved through demonstration of container closure integrity (CCI).

For vial containment and pre-filled syringe systems, it is essential to maintain drug sterility over shelf life. Ordinarily, such maintenance comprises prevention of ingress of oxygen, water, and microbes. To demonstrate this, it is essential to perform "container closure integrity testing” (CCIT), or leak testing.

With the growth of gene and cell therapies, there is an increased need to characterize container closure systems (CCS) at the low temperatures experienced during their lifecycles: ultra-low (-80°C) for genes and cryogenic (-180°C) for cells. West’s Integrated Solutions platform includes the state-of-the-art container closure integrity (CCI) capabilities needed for these therapies.