When qualifying any thermal shipping container, the three basic steps of design qualification, operational qualification, and performance qualification outlined in PDA technical report 39 should be followed.  The design qualification step should provide documented verification that the proposed design is suitable to meet the requirements.  The operational qualification provides documentation that the design yields reproducible results when exposed to expected controlled conditions (typically performed in an environmental chamber). The performance qualification is the last step and provides documentation that the design yields effective and reproducible results during actual shipments.

A prequalified thermal shipping container by definition should provide a high level of assurance that a particular shipper design will pass the operational qualification testing and ultimately the performance qualification testing. Thus, the first step of thermal shipping container qualification (design qualification) yields a prequalified thermal shipping container design.

Many companies that design and manufacture thermal shipping containers now advertise prequalified container solutions.  If performed correctly by the manufacturer, it can save you some time during the design qualification process.  You will still need to define your requirements for the shipper, but instead of performing time consuming thermal and transit testing yourself to provide documented verification that the shipper will meet your requirements, a prequalified container solution already has generic thermal and transit data for you to review and compare against your requirements.  It should be noted that any good testing data provided by a manufacturer should be performed to an industry standard such as ISTA procedure 7D and all equipment used should be ASTM D-3103 compliant (calibrated to a NIST standard).  It is also more credible when the lab performing the work is certified or accredited.  If the test data provides you with a reasonable level of assurance that the design will meet your requirements, you can move on to the operational qualification testing.

While the thought of having to go through the lengthy and time consuming process described above is often dreaded, there are good reasons to be sure your testing and qualification are thorough. First and foremost is safety to the consumer. This is especially true within the pharmaceutical industry where temperature can create conditions that affect both the safety and efficacy of the product. While it may be easy to lose sight of this primary reason to perform shipper testing, the financial exposure can be devastating, and the ethical consequences can be monumental. The other compelling reason to invest in this level of testing is that FDA requires that thermal packaging is qualified under realistic conditions to prove that products arrive unadulterated to patients. FDA audits are often dreaded, but failure to thoroughly qualify your shippers can result in a 483 warning letter detailing the processes that are not done correctly. The investment in testing on the front end will minimize the potential for this situation and ensure product viability and efficacy.

Before potential container solutions can be considered, you must first define the shipment parameters. This is true whether you are shipping internationally or domestically. The shipment parameters will help you narrow down the vast array of thermal containers available today.  Some of the parameters that should be considered are:

• Interior temperature range (i.e. refrigerated between 2° and 8° C).
• Geographical origin and destination.
• The external ambient temperatures that the container will be exposed to in the summer and winter.
• Expected duration of the shipment.
• Size and weight of the payload.
• Recipient (depot, clinic, individual etc…).
• Material restrictions (no dry ice allowed etc…).
• Shipment value (dollar cost and ability to replace).
• Expected container durability.

After defining and prioritizing these parameters, you are in a position to evaluate potential thermal container solutions that will fit your needs.  There are three basic categories of thermal containers available to consider: passive containers, active containers, and hybrid containers.

Active containers utilize electronic and mechanical means (usually compressors) to maintain the interior temperature. The advantages of these containers are their large capacity, simple or nonexistent pack-out, and the ability to maintain temperature for long durations. The disadvantages are that their moving or electronic components can fail, batteries need to be replenished, their inaccessibility to some destinations, and the very high expense associated with their use.

Hybrid containers utilize electronic controls to meter a passive phase-change material (PCM), usually dry ice, to maintain the interior temperature.  The advantages and disadvantages to these containers are similar to the active containers.  One additional disadvantage is that dry ice is considered a hazardous substance, and special precautions must be taken when utilized.

Finally, we have the passive containers, which can be further broken down into traditional and advanced thermal containers that utilize insulation and passive PCM to maintain the interior temperature. Traditional passive containers utilize some type of foam insulation and water-based gel packs or dry ice as a PCM.  The advantages of traditional passive containers are their low cost, which makes them great for short duration one-way shipments. The disadvantages are that they generally lack the duration and temperature stability required for international shipments, and they are physically large and heavy and have complex or multiple pack-outs for different situations.

Advanced passive thermal containers, like the ones developed by Minnesota Thermal Science, utilize new high-tech insulation options like vacuum insulation panels (VIPs) and custom-formulated high-performance PCMs designed to hold tight and precise temperature ranges for extended periods of time.  The advantages of these containers are their simplicity, long duration, size ranges, minimal temperature stratification within the payload area, and reusability.  The disadvantage to using these containers is that the PCM must be conditioned prior to use, so freezer equipment must be available to accommodate this step. Another challenge is receiving the container back for reuse, which increases your ROI and keeps waste out of our landfills. Reuse is certainly a challenge is some situations depending on the type of recipient, but offers a significant environmental advantage and increases the ROI.

Compare the advantages, disadvantages, and capabilities of the different types of containers available to you with the shipment parameters that you have defined to narrow down your options to the two or three that will best meet your needs. Carefully review the thermal and transportation qualification data that the manufacturer has provided and be prepared to execute some qualification testing of your own (which is another subject all together) to properly select and qualify your final solution. With proper research, planning, and execution, your international cold-chain shipments can and will be successful.