Container Closure Systems for Freeze-Dried Products
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.

Lyophilized samples in two glass vials with different heat transfer parameters were investigated with multi-scale XRM imaging.
Resources

Non-Invasive, Quantitative Characterization of Lyophilized Drug Product Using 3D XRM Analytics
Drug Development and Delivery Paper in collaboration with BMS and Moderna

Non-invasive 3D X-Ray microscopy imaging technique for quantitative characterization of lyophilized drug product
IFPAC 2021 Presentation in collaboration with Dr. Maxwell Korang-Yeboah from the FDA
Assessing the risk of changes in container closure system of a freeze-dried product on primary drying efficiency and product quality
IFPAC 2021 Presentation by Dr. Maxwell Korang-Yeboah from the FDA featuring DigiM analysis
Root cause analysis of an inverse relationship between the ice nucleation temperature of a controlled ice nucleation process, process performance and product attributes
IFPAC 2021 Presentation by Dr. Maxwell Korang-Yeboah from the FDA featuring DigiM analysis