CO2 Transmission Into Bulk Drug Substance Containers

Ingress of carbon dioxide into bulk drug substance (BDS) containers that are stored and shipped on dry ice is a serious and often understated problem. Bottles are a container of choice for freezing and shipping BDS due to their durability and convenience, compatibility with standard laboratory equipment, shelving and racking, and standard shipping containers. However, not all bottles are tested for CCI, nor does this testing guarantee leak-free performance once frozen. Carbon dioxide can readily enter bottles either through the sidewall material or, most frequently, through leaks in the closure system. This technical note outlines two studies performed by a major biopharmaceutical company to determine the closure style and torque specification of Purillex® PFA bottles required to ensure no carbon dioxide ingress during storage and shipping of BDS products on dry ice.