Before many temperature-controlled biopharmaceuticals become finished goods, their intermediate-stage bulk drug substances are shipped around the globe.Future Market Insights reports that demand for biologics is set to outpace the overall pharmaceutical industry’s growth, and global clinical trials add to the demand for robust temperature-controlled packaging.
But cold shipping presents a challenge to pharmaceutical manufacturers. “At temperatures of -80°C, single-use bags can be fragile and materials can crack. With such high-value bulk drug substances, this can cause waste in terms of materials and resources,” says Joe Cintavey, Product Manager at Gore PharmBIO Products, a division ofW. L. Gore & Associates, Inc.
Beyond product loss, bag breakage with potent drugs like cytotoxics presents an additional challenge. Drug substances continue to increase in potency. If a leak occurs, are there systems in place for cleaning both the substance and the surrounding packages in a shipment? Are personnel aware of procedures that minimize their exposure?
To target the durability issue, Gore developed its STA-PURE Flexible Freeze Container, a single-use bag designed to remain durable at cold temperatures after freezing at -86°C. The patented bag is constructed of a PTFE composite film, a fluoropolymer that accommodates a wide temperature range.
But durability isn’t the only concern the company sought to address. “Drug manufacturers are looking for pure materials in their storage containers,” says Cintavey. “Depending on the drug-package interaction, additives can leach out of plastics and affect the drug substance.”
The single-use bags feature aseptic connectors and optional single-use hardshell carriers for easier handling. These secondary packages, constructed from high-density polyethylene (HDPE), can be used in either blast or plate freezers.
Frozen bulk substances can sit for three to five years in some cases, depending on the supply chain and business needs. Manufacturers may formulate and fill in small batches, while others create large bulk volumes and pull from that supply as needed.
These practices make durability testing key to ensuring bulk drug substance packaging is up to the challenge. While each pharmaceutical manufacturer has its own protocol, Gore is aligned with handling protocols common in the industry to help ensure that the product will perform in the application, including drop and impact testing, freeze/thaw profiles, and integrity and distribution testing.