Assessing the impact of container closure systems on primary drying efficiency and lyophilized drug product quality

Container closure systems (CCS) play an essential role in maintaining drug product quality over time. For freeze-dried products, the CCS can also affect the heat and mass transfer during lyophilization and the ultimate primary drying efficiency. As a result, the CCS plays an important role in product quality and process selection. If the CCS is changed, additional adjustments in the freeze-drying process may be required to optimize the drug product. 

In this study, a systematic evaluation was conducted to understand how container closure system variables affect lyophilization formulation characteristics and freeze-drying process parameters. In addition, the vial position in the  freeze-dryer was considered in terms of its potential risk on process failure with different CCS. The evaluated CCS variables were glass vial dimensions and manufacturer, while the evaluated formulation variables were concentration of biologic drug substance, total solid content, and fill height. In addition, freezing process such as conventional freezing or controlled ice nucleation and primary drying parameters were studied in the context of the potential risk to process and product failure. The results revealed that changing the CCS of freeze-dried products without adjustments  in the freeze-drying process parameters may lead to a loss in process efficiency and product quality.