Upgrading of Traditional Cold Chain Shipping Systems Using 2-8°C Phase Change Materials

Does Your Passive Cold Chain Shipping System Use a Combination of Frozen and Refrigerated Gel Packs to Protect Your Refrigerated, Freeze-sensitive Product?

The pharmaceutical industry has seen the rapid growth of biologics, products that are typically temperature sensitive, and need to be refrigerated. This has led to increasing awareness by the regulatory agencies towards distribution practices of most temperature-sensitive products. These factors have increased the demand for better performing distribution systems and services.

An application of particular interest involves shipments of freeze-sensitive refrigerated (2-8°C) products, a category where most biologics belong to. For many years, the industry has relied on the use of water-based passive cold chain packaging systems, where water is present in both frozen and refrigerated states. These systems have suffered from important performance limitations which have resulted in heavy, large, and complicated shippers, that can transport relatively small amounts of payload, for restricted shipment durations. In addition, these systems pose serious environmental challenges, due to limited reuse and recyclability options.

The cold chain packaging industry has responded in the past few years with new solutions which use innovative technology and materials to increase performance for most applications, especially benefiting freeze-sensitive refrigerated biologics. However, these improved systems, while offering greater performance, suffer from high barriers of entry, mostly due to their high cost, which essentially requires that these systems be reused. Reusable systems can offer tremendous performance, cost, and environmental benefits, but the complexity and challenges involved in implementing return logistics programs, coupled with inherent resistance to change, constitute a very high barrier for implementation of most of these solutions.

When discussing performance improvements, thermal performance comes to mind first. However, there are additional performance areas which should not be overlooked:

• Thermal (Time/Temperature): maintaining the narrowest temperature range inside of the shipping system, and being challenged against the most extreme external temperatures, for the longest durations.
• Payload volume: supporting the greatest amount of payload for a given shipper outer volume.
• Shipper weight: having the lowest weight to reduce shipping costs and avoid the risk of operator or customer injury.
• Ease of use: implementing the simplest design for fastest, error free assembly.
• Total Cost of ownership: lowering the sum of all related costs, including material, shipping, storage, labor, conditioning, reuse, and disposal.
• Environmental/Health/Safety (EHS): addressing recyclability, disposal, toxicity, and handling concerns.

This article aims to provide an evaluation of some innovative technologies and establish whether they can be implemented leveraging existing platforms. The outcome should yield substantial performance improvements, while significantly lowering the barrier of entry, in order to facilitate their adoption in the shortest time frame possible, with minimal disruption to distribution operations.

Technology

General

Cold chain packaging systems can be grouped based on the primary technology being used to achieve temperature maintenance, as follows:

• Passive: uses phase-change materials (PCM)
• Active: uses thermostatically controlled, battery powered electromechanical heating and refrigeration systems
• Hybrid: uses a combination of both passive and active technology

The majority of cold chain packaging systems are currently comprised of passive systems, which are the exclusive scope of this article. Passive systems have two critical component types involved in preventing thermal product damage: insulation, and phase-change materials. The following are the traditional, most commonly used components and materials for each type:

• Insulation: Expanded Polystyrene (EPS), Polyurethane (PUR)
• Phase-change materials (PCMs): water (liquid or gelled, and packaged in bags, bricks, and bottles)

This article will focus on evaluating technological developments in these two areas, and propose an implementation approach. In order to do so, it will be useful to review their respective roles.

Insulation

Insulation provides product protection by slowing down the rate of heat transfer between the product and the environment, when a temperature difference exists between them. Since heat transfer is only reduced and not eliminated, insulation alone, in general, could not be expected to keep product in a shipping system within a tight temperature range (i.e., 2-8°C, a range of only 6°C) in a typical application. Using insulation alone, the temperature of a refrigerated product would continuously approach the environmental temperature (e.g., an increase in temperature in the summer, and a decrease in the winter), until equilibrium was reached. The speed of this temperature change will be affected by, among other variables, the quality and quantity of insulation used. However, even the best insulation available today, would make it impractical (from a size and cost perspective) to use insulation alone to keep refrigerated product in the relatively narrow 2-8°C range.

For insulation, technological improvements are mostly straightforward. Typically, advances in insulation mean higher insulating values, lower density, lower cost, or a combination of these attributes. In a shipping system, these can translate into increased shipping duration, or reduction of, and PCM requirements which improve weight and/or volume efficiency. The most readily available innovative high performance insulation materials, are vacuum insulated panels (VIPs). Comparatively, the average R value (R/inch) of EPS or PUR is in the range of 4-10, while VIP's claim values of 40 – a substantial improvement. In the recent past, these insulating materials have become more affordable and reliable, a trend which is expected to continue.

PCMs

Since insulation alone is not typically able to provide sufficient product protection, PCMs are utilized. A PCM can actually maintain a relatively narrow temperature range while transitioning between states (i.e., from liquid to solid, and vice versa). Unlike insulation, PCM alone, if properly arranged, could theoretically maintain a product within a given temperature range over a time period. However, since PCMs do not have unlimited capacity (i.e., latent heat), their ability to maintain a given temperature range can be greatly increased by using them in combination with insulation. Using a proper ratio of insulation and PCM can lead to much better performance, compared to using insulation or PCM alone.

How long a PCM can maintain its phase-change temperature is not the only critical factor; the actual phase-change temperature itself, among other attributes, is also critical. If the phase-change temperature is outside of the product’s acceptable temperature range, the wrong temperature could be maintained. Depending on how far the phase-change temperature is from the target range, will establish if the PCM should be used for a given application.

The shipping systems being used today for 2-8°C applications where freezing is a concern, commonly use a combination of frozen and refrigerated water. The role of frozen water PCM is to provide protection against environmental temperatures above its freezing point, by maintaining 0°C while melting. As noted, 0°C being outside of the target 2-8°C range is not ideal. In addition, frozen water PCM is typically conditioned at around -20°C, which further exacerbates this issue. Even with these notable drawbacks, ice has a lot of advantages for protecting against high temperatures: the amount of energy that frozen water can store is very large compared to other materials, and water is also relatively inexpensive, widely available, can easily be gelled, and has a great safety and environmental profile. Overall, using water for 2-8°C applications to protect against high temperatures is a reasonable choice, and does not present any clear opportunities for upgrading existing platforms.

The role of refrigerated water PCM is to protect the product from temperatures below 2°C, due to the presence of ice internally, and anticipated winter conditions externally. However, refrigerated water will maintain 0°C during freezing, and therefore will not protect from product exposure to temperatures below 2°C. Accounting for supercooling, the temperature of water can actually drop below 0°C before freezing begins, thus not really offering reliable low-temperature protection via phase change. Water’s powerful phase change is not actually being used when it comes to the refrigerated water PCM, but rather it is being used as a thermal ballast (thermal mass) to just slow down the cooling of refrigerated product. However, since it takes a relatively small amount of energy to cool down refrigerated water while in its liquid range (specific heat, compared to latent heat), it is extremely inefficient to protect from low temperatures using water. For this reason, large quantities of water, and other buffer materials (e.g., corrugated and/or insulation spacers), are often needed to try to slow down the cooling of product. In addition, refrigerated water is not always placed completely surrounding the payload, which means that external temperatures could also lower product temperatures in areas where refrigerated water is not covering, or close to, the product.

As a highly simplified example that illustrates the power of phase change compared to specific heat, if 10 Lbs of water (specific heat of 1 Btu/Lb °F) are needed in a given application, only 0.2 Lbs of 2-8°C PCM with 50 Btu/Lb latent heat would be needed to provide similar protection. For reference, water has 144 Btu/Lb latent heat, which makes 50 Btu/Lb a conservative assumption. With this in mind, using a PCM that has a phase-change temperature in the 2-8°C range to protect from low temperatures, could dramatically increase the efficiency of a shipping system.

The use of frozen water (‘wrong’ phase change temperature) and liquid water (not using phase change), are the main contributors to inefficient, bulky shipping systems. However, the least efficient component in these systems is arguably the liquid water being used to protect from low temperatures. Therefore, evaluating new PCM technology to replace refrigerated water can also clearly lead to substantial performance improvements. In the recent past, PCMs that have a phase change temperature in the 2-8°C temperature range, relatively high latent heat, in addition to good safety, environmental and cost profiles, have been developed to meet this need, and will be evaluated to establish their suitability in upgrading existing platforms.

Upgrading Existing Platforms

Due to the high implementation barrier of new high-performance technology, selecting a hybrid approach, where an existing platform is thoughtfully upgraded with some new technology, will be evaluated. For this to be worthwhile, the amount of effort must be as low as possible, and the performance benefits still substantial. An ideal hybrid implementation should alter as few things as possible relative to the existing shipper capabilities and operational processes, and total cost of ownership, in addition to maintaining the current single-use disposable process. The new technologies identified earlier will be evaluated to establish their suitability for a hybrid approach.

VIP Suitability

Vacuum panels are very attractive components due to their excellent insulating properties. Because of this, using systems which leverage them could be a good approach, as long as the implementation barriers are acceptable. However, generally speaking, these are not acceptable, for the following reasons:

• Cost: vacuum panels are much more costly than traditional insulating materials which in most cases, in order to be competitive, require that shipping systems be reused.
• Fragility: vacuum panels are much more fragile than traditional technology. While this can be managed, it can lead to changes in the shipper’s design, and possibly operator handling and assembly requirements.
• Customization: it is possible to customize panels to a wide range of sizes. However, because of tooling and production constraints, customization can further increase costs, unless production volumes are very high.
• Shelf Life: especially in the context of reuse, shelf life can be a significant aspect that needs to be managed. Performance of the VIPs can be affected due to damage, or due to changes over time (anticipated loss of vacuum). Therefore, testing prior to reuse, and maintenance of a system for tracking expiration dating impose additional implementation barriers.

Because of these difficulties, the use of vacuum panels is not recommended for upgrading of traditional platforms in a hybrid approach. This said, systems using VIPs can be great alternatives if the implementation of a closed-loop system is possible, or if the application justifies the increased costs.

2-8°C PCM Suitability

When first available, 2-8°C PCM suffered from similar issues as VIPs. Specifically, these materials were also costly and difficult to customize. The cost was driven by the relative high cost of the PCM itself, but also due to the cost of its rigid packaging, typically blow-molded bottles. This also made customization complicated and lengthy. In addition, bottles reduced the efficiency of the PCM, due to the thickness and weight of the bottle, the difficulty in surrounding a payload in multiple sides, and the complexity of completely filling the bottle with PCM.

However, in the recent past, 2-8°C PCM has become available contained in flexible packaging – think bubble wrap, filled with 2-8°C PCM instead of air – which provides the following benefits over rigid packaging:

• Cost: reduction in manufacturing costs due to the use of thin films in high throughput production equipment.
• Customization: equipment is available which can easily change the width, length, weight of the overall component, and weight of the individual pockets of PCM. This allows flexibility to easily replace existing configurations of refrigerated water PCM, in an expedient and cost-effective manner.
• Thermal (Time/Temperature): flexible packaging can improve coverage to all six sides of a payload since these can be covered using only two components (by folding one component into a ‘U’ shape, three sides can be covered with each component), can be filled almost without air since PCM pockets can be completely filled, and can allow more efficient heat transfer between the PCM and the product because of its thin walls.

Therefore, 2-8°C PCM packaged in a thin, light, cost-effective format that evenly distributes PCM around a payload is a great candidate for use in a hybrid implementation. Insulating components and frozen components can stay the same, while the refrigerated components are the only ones that need to be replaced, minimizing disruption.

Performance Improvements

Replacing refrigerated water with a 2-8°C PCM in an existing platform can yield significant performance benefits. These would include one, or a combination of the following, depending on the application:

• Thermal (Time/Temperature): replacing the refrigerated water components with similar quantity of 2-8°C PCM, would greatly increase the available protection against low temperatures. This means that tighter temperature control could be possible, certain winter conditions could be endured for longer durations, or that colder temperatures could be endured for the same durations, or a combination of these.
  • In some applications, the thermal performance gain could be sufficient to allow the conversion from seasonal pack-outs to universal.
• Payload volume: the amount of space required by the 2-8°C PCM will be less than that required by the refrigerated water, without affecting performance requirements, thanks to the use of phase change. With this in mind, the payload could be significantly increased.
• Shipper weight: similar to payload volume, a reduction in total system weight could be achieved by replacing refrigerated water with 2-8°C PCM, while maintaining thermal performance.
• Ease of use: since two 2-8°C PCM components could cover all six sides of a rectangular or square payload, if the current water PCM consists of six components, these could be replaced with two components, making assembly simpler and faster.
  • In addition, depending on the application, it is possible that the 2-8°C PCM could be used without requiring of any conditioning (i.e., refrigeration at 2-8°C); this means that it could be stored at room temperature (e.g., 20-25°C). Since the 2-8°C PCM is thin and light, and would not go through phase change when cooling from room temperature to 2-8°C, the equilibration of these components would be expected to take place fairly quickly. This would have a very positive impact from an operational and cost perspective.
• Total Cost: a shipping system’s total cost of ownership is comprised of not only material costs, but also shipping, labor, storage, and conditioning among others. In most cases, material costs can be expected to increase; however, when evaluating total cost of ownership, cost reductions are likely.

While great improvements can be achieved with this approach, there are some aspects to keep in mind when considering the use of 2-8°C PCM:

• Conditioning: if conditioning is required to be at 2-8°C for a given application, since the PCM must be liquid prior to assembly, care must be taken not to freeze the PCM during conditioning in the refrigerator.
• Assembly: if conditioning at 2-8°C is required and assembly takes place at room temperature, assembly should be completed as quickly as possible so that the 2-8°C PCM components do not warm up to an unacceptable temperature.
• EHS profile: while 2-8°C PCMs are considered non-toxic and can typically be disposed of in normal waste streams, these materials have a less favorable EHS profile when compared to water. With this in mind, the user should understand the effects of possible leakage, and any local use, transport, and disposal regulations.

Summary

Innovative technologies can offer great performance improvements, but are difficult to implement since they often need to be reused. However, existing passive cold chain shippers using refrigerated water in 2-8°C applications with freeze sensitivity, by replacing the refrigerated PCM water components with 2-8°C PCM in flexible packaging can significantly improve their performance, with minimal disruption.

The biopharma industry needs to continue to challenge cold chain packaging suppliers to assure further development of flexible packaging for phase-change materials, in order to keep reducing costs and improving performance and flexibility. The proposed hybrid approach should be considered a bridge towards full implementation of reusable systems that improve quality and performance, while reducing costs and environmental impact.