Amgen Develops Reusable Shipper For Frozen Payload

Faced with the need to transport large quantities of a deep frozen drug substance, Amgen Cold Chain Engineering (Thousand Oaks, CA) developed a custom insulated shipping system working with Entropy Solutions (Minneapolis).

Amgen required a shipper that could hold a minimum of 80 one-liter bottles with the ability to maintain < 20 degrees C for a minimum of 60 hours. The container had to support packing out in a controlled room temperature environment. Using dry ice was not an option as exposure to C02 is known to cause a pH shift in the drug substance. Also, the shipper had to fit in a LD3 air cargo shipping container.

“Developing large shippers is well within our capabilities. Making it fit into an LD3 container was bit more challenging, but doable,” says Brian Wallin, senior engineer, Amgen Cold Chain Engineering.

“That no dry ice could be used in the shipment made the problem statement for this particular project much more difficult than anything we had tackled before,” Wallin adds.

Amgen initially sought to use their existing shipper designed to work with gel ice that froze around minus 50 C. “We tried sourcing a new ice that phases at or near minus 50 C (but) our initial test quickly proved to be completely inadequate,” Wallin says.

Entropy was developing a new pallet sized shipper for 2 to 8 C, and had just successfully formulated PureTemp minus 40, a PCM for maintaining deep frozen status around minus 40 to 45C. Amgen asked Entropy to test the pallet shipper with the minus 40 PCM using Amgen’s product load requirements.

“The initial design vastly outperformed our previous attempts, and showed that, with refinements in the packout design, we could meet all of our requirements,” Wallin says.

The design qualification process focused on determining a payload volume that would meet Amgen’s needs, and the appropriate configuration and placement of the PCM panels. Specific design and material properties had to be considered as the one-liter polycarbonate bottles are housed in stainless steel totes. The secondary packaging was designed to have a single tote accommodate either Amgen payload or a PCM.

The pallet had to be maintained in an upright position. This required a system to maintain equal payload volumes and masses at different temperature ranges using PCMs with different phase points and internal configurations, Wallin says.
Thermal testing showed that with the PCM panels configured in a certain way, the unit could maintain Amgen’s narrow temperature range and time requirements.

Qualification of the container following the CDER validation principles (CQ, OQ, and PQ) demonstrated the shipper met worst case thermal and physical challenges under normal conditions consistently and repeatability, Wallin says.

“In the end, we met and exceeded all of our goals. The shipper’s minimum qualified duration far exceeds the required minimum (for providing) adequate insurance in the event of (shipping delays),” Wallin says.

As an added bonus, the durable unit will withstand multiple uses allowing for significant cost savings in shipping costs, Wallin adds.