Medical Device Link.

Pharmaceutical and Medical Packaging News Magazine
PMPN Article Index

Originally Published February 2000

SPECIAL

Packing for a Safe Trip

by Daphne Allen, Editor

Blood. Donor organs. Vaccines. Biochemicals and reagents. Transporting such temperature-sensitive items has traditionally involved packing them into disposable polystyrene, adding frozen ice packs or dry ice, and rushing them across the miles to their final destination. This method has worked well for many companies and products over the years, provided that the items do not need to remain within a particular temperature range for any great lengths of time or distance. However, recent advances in transport materials and services are allowing product manufacturers to use more-efficient and less-hazardous transit means.

These new advances range from film-covered polystyrene to vacuum insulation panels (VIPs) to pallet-sized shipping containers. Even traditional insulated containers made with polystyrene and polyurethane have improved a bit. Despite their material or structural differences, all aim to increase insulation and strength, which can in turn lead to other benefits, such as the use of cheaper shipping services, the reduction of temperature-related damage, and the elimination of hazardous materials like dry ice.

The radiant barrier film covering DHL's ThermoExpress shipper reflects heat and can be supplied with a holographic pattern for embedding codes.

Packaging engineers will have plenty of guidance in evaluating these new options—in 1999, the International Safe Transit Association (ISTA; East Lansing, MI) released two test projects for thermal performance testing of transport packaging solutions.

ECONOMICAL FARES

Molded expanded polystyrene (EPS) is the most commonly used material for shipping containers, insulating its contents from extremes of cold or heat for short durations. Standard containers usually have R-values (a measure of resistance to heat transfer) of about 3 to 4 per in. Tom Pringle, CEO of Insulated Shipping Containers Inc. (ISC; Phoenix), says that conventional molded EPS containers equipped with refrigerant can keep most temperature-sensitive goods within their required tolerances during overnight delivery. Most of the industry operates exactly this way—by placing the product into a $5–$10 container with frozen ice packs and paying for expedited delivery.

Newer containers promise to protect products for even longer periods of time with less refrigerant, enabling companies to reach more-distant markets or to ship using a more-economical service. Generally speaking, these newer products fall into two categories: redesigned conventional foam containers insulated with film and containers incorporating vacuum-insulated panels. In addition, containers relying solely on conventional shipping materials like polystyrene and polyurethane have also been redesigned to increase insulating capabilities.

Polystyrene. In an effort to develop shippers for perishable healthcare products that could work just about anywhere in the world, DHL Airways Inc. (Redwood City, CA) devised its ThermoExpress line of shipping containers for use with its door-to-door express delivery system. The shipper consists of closed-cell extruded polystyrene laminated to the interior of a standard corrugated box that is covered with metallized radiant barrier film. This film reflects 97% infrared radiation to generate minimal internal heat, helping to keep internal temperatures stable even in direct sunlight. According to Greg Johnson, DHL's product development manager, heat transfer is so low that it cannot be detected by infrared photography.

Standard EPS foam containers themselves have even undergone a transformation. Polyfoam Corp. (Northbridge, MA) redesigned the construction of its EPS foam containers in order to outperform standard EPS containers. The Thermalok 1½-in.-thick EPS containers feature internal side-wall channels for more-uniform temperature control throughout the container and special stand-off floor pads to keep the product free from condensation. The lid fits securely through friction, and a tongue-in-groove interlock design minimizes heat loss. Because Thermalok has just been introduced, the firm has performed limited comparative testing, but Fred Scott, vice president of sales and marketing, expects it to outperform its previous line of EPS.

Polyurethane. GDHS Strategic Development Group (Barcelona, Spain) has just launched a new line of polyurethane-insulated containers. Its Friobox Express container combines high-density polyurethane foam with two special aluminum bags that act as both insulators and barriers against leakage. The entire system is housed in a white corrugated container. The system is supplied flat and vacuum sealed, allowing users to store several unused containers in a relatively small amount of space. Once it is assembled, users need only to place two special cooling elements (which prior to use are filled with water and frozen solid) in a cube around the product being transported and then seal the box. Brendan O'Donoghue, GDHS public relations manager, states that the boxes have been tested successfully by the German government's IBMB Institute. O'Donoghue also states that even with a continuous ambient temperature of 30°C, a Friobox Express chilled container will maintain product temperature in the range of 2° to 6°C for 96 hours, while the frozen container maintains product temperature in the range –25° to –18°C.

The four-layer Deep Chill shipper from Polyfoam Packers isolates the VIP panels from external hazards.

Envirocooler, a division of Foremost in Packaging Systems Inc. (Santa Ana, CA), has also redesigned traditional polyurethane shippers in order to protect products during extended shipping times. Manufactured with water-based insulating foam, its environmentally friendly system has been tested independently following ASTM method D3103 and has been shown to keep items at their desired temperatures significantly longer than EPS-based products, claims Rodney Derifield, the firm's CEO. For instance, a container with a wall thickness of 3 in. can keep items at temperatures between 0°C and room temperature for 96 to 120 hours using a gel pack.

VIPs. While these new containers rely on an established staple like polystyrene or polyurethane, Dow Chemical (Midland, MI) decided to revamp the core technology—literally. While most foam-insulated shippers are made up primarily of closed-cell polystyrene, which reduces or delays heat conduction and convection by capturing and containing the gases used to make the foam in the cell of the polystyrene, Dow instead forged an open-cell formulation. "The open-cell design is needed in order to evacuate the molecules," explains John Hagen, technical sales specialist/application engineer for Dow's Fabricated Products Business and Research Center. "This eliminates conduction and convection. There are no particles to collide to transfer heat." VIPs typically offer an R-value of 20 to 30 per in.

The open-cell foam, called Instill, is placed along with water- and gas-adsorbing materials into the walls of the package and enclosed under a vacuum. As long as Instill remains under a vacuum, molecular movement and collision is minimized, reducing heat transfer.

Dow is currently supplying Instill VIP core to several shipping container manufacturers for the medical and pharmaceutical industries, including ISC, Thermo Solutions Inc. (Minneapolis), and Polyfoam Packers Corp. (Wheeling, IL). Each of these companies has incorporated VIP technology into its own shipper designs.

Originally using Mylar reflective materials along with traditional insulating materials, Thermo Solutions decided to work with Dow to make the ultimate high-end container. Last October the firm introduced square VIPs designed to transport refrigerated and frozen products. The panels are surrounded by either a hard plastic shell, a nylon material, or a corrugated box, depending on the end-user's requirements. "Until recently, a square vacuum package hasn't been available," says Curt Hanson, vice president of sales, pointing to such classic examples of vacuum insulators as the thermos and the cryogenic dewar. Until Dow's introduction of VIPs, square vacuum packages weren't possible, because, Hanson explains, "Once you pumped all the air out, the pressure was so great at the corners that the walls would collapse." With Dow's help, Thermo Solutions used a number of individual VIPs to make a square vacuum package.

Hanson had a client that needed to ship its biotechnology products at a temperature between 2° and 8°C. The client's independent testing proved that it could maintain such a temperature for 5 days. "The VIP product far exceeded this requirement," Hanson explains. "It would have taken a 7-in.-thick layer of EPS to meet the capabilities of the VIP."

Another of Thermo Solutions's clients had an equally challenging project. SulzerCarbomedics (Austin, TX) needed to ship temperature-sensitive biological products for clinical trials. "We tried a standard EPS foam with a corrugated box and ice packs, but this configuration did not work," says the firm's senior packaging engineer Brett White. "We set up an environmental control chamber at 120°F and tested to see whether the package inside the EPS would exceed 100°F in 48 hours. We were unable to meet the test requirements." After switching to Thermo Solutions's VIP product, however, White exceeded his requirements. "We were able to maintain an internal temperature below 100°F at 120°F conditions for 5 days," he says.

VIP technology is ideal for high-value, temperature-sensitive products like these and others, such as serums, proteins, and reagents, says Kevin Grogan, market manager for Polyfoam Packers's Scientific and Medical Products Div. Using conventional technologies, "companies often pay for special couriers to meet planes during international shipments in order to repack the products upon arrival. The product can then maintain its target temperature through customs and ground shipment," he says. But with VIP technology, the shipping requirements change. "We are seeing amazing results. Products are maintaining their temperatures for 5 days in the VIPs with only gel packs."

Grogan admits that VIPs do have one significant technical weakness—if the panel loses its vacuum, there is a significant drop in R-value. That's why Polyfoam, primarily a molder of EPS, has combined both EPS and VIP technology into its four-layer Deep Chill shippers. The innermost layer consists of a 1/8-in.-thick corrugated liner, designed to keep the products from damaging the VIP. The next layer is the 1-in.-thick VIP, providing an R-value of 30 per in. Next comes a 1½-in.-thick wall of custom-molded EPS. "This protects the vacuum panel from the hazards of the shipping environment," Grogan explains. Finally, an outer corrugated shipper houses the three layers. Hanson of Thermo Solutions adds that its hard plastic shell for its VIP shippers also protects the panels from shipping hazards.

ISC as well has taken such weakness into account during the design of its VIP shippers. "We have a container in development that not only protects the panels but incorporates a patented vacuum indicator on each panel to indicate whether the panel is deflated prior to its use and reuse," says Pringle. "Our patented indicator concept gives the user the confidence that the panel is evacuated prior to use—sort of like checking your tires for inflation before you drive—but in this case you visibly check the deflation of the panels prior to each shipment."

Instead of deflation risk, Pringle points to another VIP weakness limiting their market penetration—cost. "The cost of VIPs means you've got to get the shippers back and reuse the VIPs as many times as possible to make them cost-effective," he says. "These specialty-type VIP panels cost several times more than EPS and two to three times the cost of polyurethane."

Thermo Solutions's VIP shipper, shown here with a nylon cover, can be reused.

Polyfoam's Grogan admits that cost hinders some companies from investing in VIPs. "VIPs compete better with molded polyurethane containers than they do with EPS. A urethane container with 3-in.-thick walls costs $30–$40, while our Deep Chill container with 2½-in. walls may cost up to 50% more."

Pringle believes that a cost reduction could encourage companies to move from their existing proven methods and conventional systems. "However, until the VIPs are made for mass consumption for other thermal applications, like insulation walls for refrigerators, freezers, cold-rooms, refrigerated trucks, and the building industry, the panels will continue to be too variable in quality and too expensive to use for shipping containers in the majority of the distribution industry. Until then, they will be used primarily for specialty requirements in lower-volume applications."

CLIMATE CONTROL

With these new insulating capabilities, suppliers say that shippers can reduce the amount of refrigerant needed to preserve products during transit. This is good news for companies that are grappling with some of the problems associated with dry ice.

Because dry ice can burn and restrict the respiration of animals and humans, it is considered to be a hazardous material and thereby requires special handling and training of the packaging crew. Packages must be specially designed "so that the CO₂ vents without a problem and the package is strong enough so that it prevents wet seams from the dry ice evaporation and condensation," says Pringle.

Once these issues are addressed, however, there remain other pressing ones. "Its use is restricted on airplanes," explains Johnson, whose company, DHL, does not permit dry ice shipments on its international flights. Domestic flights typically limit dry ice to 10 lb per container. Also, dry ice shipments can be bumped from commercial airline flights when carrying live animals or if the manifest shows dry ice quantities higher than deemed safe by the airline or even the pilot, adds Pringle.

In addition, it is "hard to control the temperature of containers packaged with dry ice for any length of time," explains Sanford Cook, president of TCP Reliable (Edison, NJ). Johnson agrees. "Dry ice lasts at a rate of 5–6 lb per 24 hours, depending on the container and the environment," he says. "Dry ice sublimates—goes from solid to gas—so the temperature inside the box will go up in a short period of time."

Pringle disagrees. "Dry ice will not sublimate very quickly if placed in an efficient thermal container. We had a New Zealand lab customer send a lab sample with 25 lb of dry ice to Norway in our E-90 polyurethane container with 3-in.-thick walls. It got stuck in India and in Frankfurt, and when the lab in Norway got it 9 days later, there was still dry ice present."

Nonetheless, several companies have developed alternatives. Polyfoam Packers, Thermo Solutions, DHL, TCP Reliable, Gel-Pak (Sunnyvale, CA), and Cryopak Industries Inc. (Vancouver) have all invested in the development of new phase-change materials intended to replace dry ice.

Thermo Solutions's phase-change material, EverKool, is designed to begin melting at –11°F in order to maintain frozen products. Hanson says that, when used with the firm's VIP container, "the combination is at least seven times more effective at keeping an acceptable temperature range for a significantly longer period of time when compared with alternatives."

DHL offers refrigerant packs in three different temperature levels—fresh, frozen, and negative frozen. A 0°C phase-change pack protects products at freezing temperatures, and a –20°C pack accommodates negative freezing requirements. Each features a specially designed outer layer that absorbs moisture and reduces condensation damage in transit.

From top: Three components (polyurethane, an aluminum bag, and a water-filled element) give Friobox Express its insulating power. Images courtesy GDHS Strategic Development Group.

TCP's phase-change packs go even lower. Three versions are available, in –20°, –50°, and –75°C, the lowest of which is intended to preserve tissue, organs, and biotech materials.

Pringle isn't completely convinced of the effectiveness of phase-change packs. "The new phase-change products used in conventional EPS-insulated containers do not always last at their phasing temperatures as long per pound as dry ice and therefore require a larger amount of packs and a very efficient thermal container to provide more than 24 hours of temperature stability in transit. Also, it should be kept in mind that the lower-phasing gels require freezing at temperatures lower than their phase-change temperatures, and this can be a problem in some cases when the typical commercial freezer at –18°C is used to freeze a –20°C gel pack." However, for some products sensitive to dry ice, Pringle admits that "they are the only things that will work and, if designed and tested properly, they work very well."

Because some products need to be maintained at room temperatures or higher, phase-change materials that phase at and emit warmer temperatures are available. TCP Reliable offers formulas marketed as Exo-Gel that are designed to maintain temperatures as high as 50°C. One of its formulas was able to provide a temperature plateau of 24°C for living cells during shipment from Maine to both Australia and Alaska.

LARGER LUGGAGE

If pharmaceutical packagers aren't interested in any of these new solutions for individual shipping containers, TCP Reliable has another solution. The firm has forged a partnership with KLM Cargo to develop door-to-door, environment-controlled shipping modules. Designed to maintain any temperature between –50° and 50°C, the modules are constructed of phase-change materials and supporting materials and housed in metal. "You can drastically reduce the costs of secondary shipping containers because you rely on the modules, not the packages, for protection," says Cook. "It really does eliminate the need for secondary packaging like polystyrene and polyurethane." The modules protect contents from temperature and humidity as well as from shock and vibration.

The service, called Nightingale, can accommodate both small and large product volumes. "The modules can hold volumes from a few packages to up to two pallets' worth," Cook says. "If companies have enough volume, they can take up an entire module; if they have small volumes, special trucks equipped with modules can pick up packages for delivery to airports, where the packages will be placed into other modules." Some firms may even have high enough volumes to warrant custom designs.

Cook envisions the modules to be part of a "tunnel" concept, in which protection is provided at every stage of distribution. "Temperature control starts at the storage facility and continues on the Tarmac and through customs. There are no gaps."

TESTING METHODS

Regardless of what option packagers choose, they will need to test it under the extreme conditions found in the applicable transit environment. This involves testing packaged products in environmental chambers at conditions that companies expect the shipping container to be exposed to in transit.

Last year ISTA released two test projects intended to guide companies through such testing. The first one, ISTA 3G, "Thermal Performance Testing of Transport Packaging," is designed "to measure the relative ability of a package to protect a product when exposed to test cycles that simulate ambient exposure of extreme temperature conditions." It includes various intermittent sequences of atmospheric testing, shock conditioning, and vibration conditioning.

"The idea is to challenge a package in the same way it gets challenged during shipping," explains Dennis Young, a transportation packaging consultant based in Grand Rapids, MI. "When a package goes through hazards, the hazards affect the package's ability to do its job, which in this case is to protect products from extreme temperatures. Project 3G combines temperature testing with dynamic conditioning. Most users will continue to do separate dynamic tests, vibration, drop, compression, in addition to this Project."

Envirocooler's Derifield likes this approach. "Shock and vibration affect the temperature maintained by a container. The refrigerant can migrate in the container and either freeze a product that is not supposed to freeze, or dry ice can break into small pieces that sublimate faster. Temperature, shock, vibration, and rotation are dynamic and interrelated; and to test them in static states, independent of each or all of the other factors, is a gamble I do not believe is worth the potential risks."

Pringle, however, points out that performing thermal testing and shock and vibration testing at the same time may not be practical in all cases. "The thermocouple probes placed in product inside syringes or small ampules can easily be displaced by shock and vibration testing, rendering the test invalid, since the data will not be accurate for product temperatures. Also, the ambient test temperatures may not be maintained since the containers that are in test in a chamber at high or low temperatures will have to be removed from the specified ambient temperature to do the shock and vibration testing, which is normally conducted in a room-temperature environment." Pringle believes that the project will be revised taking these considerations into account before July when it will become an accepted ISTA test method, and Young agrees that these changes are reasonable and likely.

The method ISC's clients find most effective involves qualifying a thermal container to hold a required temperature, then testing it dynamically mid-way through the transit cycle. "If product damage is found after testing, then the packing configuration can be modified, requalified thermally, and then retested dynamically," Pringle explains.

The second project, ISTA 5B, "Focused Simulation Guide for Thermal Performance Testing of Temperature-controlled Transport Packaging," includes guidelines for companies that wish to set up their own individualized test method. "It's not really a substitute for 3G, but rather an adjunct," Young says.

Many shipping container suppliers offer such testing as part of their services. Also, among ISTA's members are more than 80 third-party laboratories, many of which are capable of performing temperature and dynamic testing.

IDEAL SOLUTIONS?

Standing in the way of wide acceptance of many of these new solutions are two very significant obstacles: the costs of initial investment and revalidation. "Revalidation is a painful process," explains Sharon Jaeger, a packaging engineering consultant for Farron Associates (Mission Viejo, CA). "A change in transit packaging would have to represent a cost savings in shipping, but often the change costs more." While Jaeger calls new transit shipping containers like VIPs "an improvement" to the current state of the art, she doesn't feel that there is "an impetus to move to them, unless a company is having extreme problems with its current shipping mode or it has a high-end product to protect."

However, industry is always looking for something better. "Most shipping departments are looking for the magic solution of a thermal container that folds flat, is as thin as a corrugated box, and takes little or no refrigerant to hold the temperature of products in transit," says ISC's Pringle. "There is no such animal. However, because of the desire to find this magic solution, industry ears are open to practically any solution that sounds good."