Medical Device Link.

TRANSPORTATION PACKAGING

Many active systems for transportation packaging, like Envirotainer’s RKNe1, are self-contained units that allow users to load product quickly with little to no assembly.

As pharmaceutical companies scrutinize their cold-chain distribution, the benefits and drawbacks of active versus passive shipping solutions have to be considered.

Healthcare companies have tended to favor passive systems, finding them more reliable and easier to qualify.

Yet active systems also offer advantages. They do not require warehousing and assembly of packaging components. Battery-powered systems can be recharged to support transport over longer routes. Active-pallet shipper solutions that keep product safe under cold ambient temperatures using heating and high-performance insulation address requirements for tight temperature control through extreme conditions.

Companies are evaluating packaging alternatives more closely. And the increase in global shipping and new regulatory guidances and laws in the United States and abroad have spurred firms to validate packaging according to more precisely defined distribution conditions, says Kevin O’Donnell, technical manager, ThermoSafe Brands (Arlington Heights, IL).

“Companies are looking to move large amounts of bulk product between countries. This is a unique market that didn’t exist seven or eight years ago. Increasingly, they want to test packaging against transportation profiles they develop through their own data collection. And they will look to apply active or passive packaging to their standards,” O’Donnell says.

A key advantage of passive systems is that they can hold temperatures under year-round conditions. “There are no seasonal issues with passive systems, and package sizes are limitless as well,” says O’Donnell.

Companies such as ThermoSafe Brands, Envirocooler (Huntington Beach, CA), and Cold Chain Technologies (Holliston, MA) offer pallet-sized solutions with universal packouts for summer and winter conditions. Shippers maintain constant internal temperatures by precisely calibrating premolded insulation, and the volume of the energy source.

Envirocooler uses heat conduction and convection for a constant rate of heat transfer and temperature maintenance in its BioSphere with frozen gel packs for LD3 freight containers and the Cryosphere with dry ice for AMJ freight containers, says Rod Derifield, CEO.

A premolded urethane Ice Locker separates frozen gel packs or dry ice from the payload. Air Lock interlocking friction-fitted walls, lids, and bases reduce external convection. A Convection Engine with molded cavities or channels disperses internal air more uniformly, which controls the initial shock and energy from frozen gel packs.

“The Ice Locker generates cold mostly through thermal conduction, which slows down the rate of energy transfer. You then want to balance [that decrease in] the rate of energy transfer with the need to get the optimal amount of energy released from the source. The Convection Engine opens up the valve a little bit, allowing some air to pass over the surface of the gels to optimize energy released, while the Ice Locker controls energy transfer,” Derifield says.

The BioSphere LD3 shipper holds 2° to 8°C for up to 267 hours in monitored line shipments. “In test labs, where we have stressed it under different customers’ profiles, we are achieving in excess of 120 hours in all cases,” he says.

Cold Chain Technologies offers the va-Q-tainer, a prequalified, universal shipper system that holds 2° to 8°C for up to four days. Available in two sizes for U.S. and European pallets, the passive system combines rigid multilayer outer walls with high-performance vacuum-insulation panels lined with form-fitting phase-change materials.

“Most of our customers ship to Europe and back, which is well within our time frame,” says Larry Gordon, president.

MECHANICAL RISK

In contrast, many active shippers have not been tested or verified to work under cold profiles. “Using active systems that support only cooling can be a real risk in cold environments. Most of these units have some insulation, but not enough to protect the product if you are trying to keep it just above freezing. If you want to maintain 2° to 8°C, and it’s –20°C outside, you run the risk of freezing your product,” says O’Donnell.

Another key concern that drug firms have with active systems is the risk of mechanical failure. “With passive systems, you have eliminated mechanical risk. Performance is repeatable, based on assembly,” says O’Donnell.

Active systems rely on batteries, compressors, generators, thermostats, and fans. These can wear out or break down. And qualifying these mechanical components is problematic, says Derifield.

“Regulatory bodies are saying that if you are qualifying units, you have to have good theory. You have to know what individual parts and components you are qualifying and why, and make sure that, over time, your qualification of those units and components is still valid,” says Derifield.

“Active units have mechanical and motorized components that wear out. When a pharmaceutical company has one of these shippers delivered, every piece of that mechanical unit should be verified, because every time it is used, to some degree it changes. This has become a sensitive issue. End-users are faced with having to verify that all the components work as they did when the unit was first qualified in a test lab,” he says.

Lane segment availability is another drawback of active systems that must be considered. Units might not be immediately available for shipping between secondary hubs. And, “when you have to move containers, somebody has to pay for it, and it won’t be the [container manufacturer],” says O’Donnell.

Envirotainer’s RKNe1 pallet-shipper uses electrical heating and compressor cooling to protect cargo for up to 38 hours in extreme cold without battery recharging.

Most active-pallet shippers use circulating fans to draw air through bunkers containing dry ice. Systems may require reicing as the dry ice is used up in containers with minimal insulation. Also, “the volume of dry ice is well below the maximum of what an aircraft can carry. But it is still up to the pilot as to whether he wants to allow Class 9 hazardous material on his plane. Your cargo could be bumped at the last minute,” he says.

A major advantage of active systems is they avoid the need for warehousing components. Passive systems feature multiple components, and they require longer assembly times and gel-pack conditioning. With active systems, unitized product can be quickly loaded and unloaded. And fiberglass or metal construction and locking mechanisms make them more secure than typical corrugated boxes and foam, O’Donnell says.

“Most active shippers are self-contained LD3 and LD9 units designed for air transport. Passive systems are consolidated with other freight on a cookie sheet,” says O’Donnell.

Makers of passive systems have sought to address inventory and assembly issues by focusing on ease of pack-out and reducing weight and bulk. Prequalified systems target specific shipping profiles.

The Time Saver prequalified shippers from TCP Reliable Inc. (Edison, NJ) are designed to hold varying temperature ranges in windows from 24 to 120 hours. “Companies want cost-effective designs that are simple to implement. The majority of our drug firm customers are looking to ship in 72 hours or less,” says Bill Hingle, marketing manager.

TCP Reliable’s Time Saver 72 uses the Phase 5 refrigerant that requires “a much smaller volume of material than conventional gel packs. Using Phase 5 in designs configured to customers’ needs, we are able to reduce the size and weight of packaging. Our Thermal Control Panels provide this flexibility in various pack configurations,” says Hingle.

Cold Chain Technologies offers “a quick simple pack-out process with both our vac-Q-tainer and Kool Temp GTS prequalified shippers. The vac-Q-tainer substantially reduces labor-intensive handling and consumption of nonreusable packaging materials, while the GTS features an easy pack out and replaceable components,” says Gordon.

ThermoSafe’s line of shippers and containers includes the DurableTransport units, which are durable containers that are efficiently packed out and unloaded. The reusable units feature double-walled polyethylene filled with urethane foam and the Flex-Seal lid and container system. In models with fiberglass outer construction, a polyester gel coating enhances durability. Providing an R-23 insulating value, ThermoSafe’s Pallet Shipper-PUR line employs a rugged corrugated outer casing and rigid polyurethane insulation, with refrigerants. Cargo is protected under moderate and extreme temperatures for up to five days in transit. The reusable six-piece design is quickly assembled and folds flat for storage and return.

ISTA’s 4AB Protocol Offers Custom Test Plans Based on Measured Data Pharmaceutical and medical device companies—in refining transportation packaging requirements—are, to an increasing extent, compiling real-world data on the stresses to which packaging is subjected. The Project 4AB testing protocol under development by the International Safe Transit Association (ISTA) provides shippers with measured field data for lab simulation tests in a computer-aided, Web-based model. Bill Kipp, associate executive director, ISTA, says 4AB has been in alpha test for over a year, with a beta release set for later this year. “The more companies know about their distribution environments, the better simulations they can perform. But simulations then become more and more complicated, and printed procedures can be time-consuming and intimidating. We have sort of reached the limit of what people can cope with. With 4AB, most of the complexity of translating field data into test parameters takes place behind the scenes,” Kipp says. Many companies use ISTA’s Focused Simulation (FS) guides for developing test protocols when they collect their own field data to refine measurement and testing of specific environment factors. “4AB is actually a step below FS. But the FS protocols are not actually tests. They are guides for putting together your own tests, after the user has determined hazard levels. FS is a DIY project. Few people do total FS programs, because they are costly and time-consuming,” Kipp says. Shippers often use FS tests to tweak General Simulation tests (3 Series). They will measure elements and develop their own tests using the FS guides when they are incurring environmental damage outside the range of parameters defined in general simulation. “4AB is the best test we have in a self-contained testing protocol. The 3 Series doesn’t ignore the real world, but the sequence and intensities of hazards are defined in a broad-brush, simplified way,” Kipp says. In 4AB—or Enhanced Simulation—the software prompts users to define their distribution pattern with as much detail as possible. Companies could enter factors such as distribution center stack heights, rack systems, vehicle suspension systems, and road types. Then 4AB draws on a Data Depot containing up-to-date information on environmental conditions. The Depot includes weather patterns from the National Oceanographic and Atmospheric Administration. “We have truck vibration data from Thailand that was published in the Journal of Packaging Technology and Science. If you are shipping to Brazil, the program will have Brazilian data. In most cases, the data have been published somewhere. But you have to be aware of it, collect it, analyze it, and translate it into a format that can be used as a test specification in a laboratory,” says Kipp. Data are translated into custom test protocols covering all the segments of a user-defined hazard sequence. Many calculations occur in the background. “In configuring a compression test for corrugated packaging, for example, we solve four formulas simultaneously, for dependency on temperature, humidity, time-in-storage, and stacking patterns,” he says. Kipp says early adopters of 4AB will be in nonregulated industries. Pharmaceutical companies will be more cautious in changing protocols based on updated field data, since FDA looks for consistency in package testing. “Companies could generate a plan, freeze it, and then work that protocol with FDA,” says Kipp. “4AB is really exciting. As a Web-based application, it can be accessed anywhere. You will be able to store your profiles and have a direct contact with ISTA for support,” says Mark Escobedo, chief technologist for Westpak Inc. (San Jose, CA). “These measured data have been lying around for years, but nobody has combined it all together into one big database. The protocol will simulate as much or as little of the distribution environment as you put into the system. With the 2 and 3 Series, you might be overtesting and packaging for conditions that don’t really exist in the field. 4AB will tell me ‘you will get this type of vibration.’ “This will increase the value that we can provide to our customers, because we can more closely simulate what their product is actually going to see in distribution,” Escobedo says.

STANDING UP TO COLD

Envirotainer (Sweden) and AcuTemp (Dayton, OH) have added heating and insulation elements respectively to active-pallet shipper solutions for performance in cold environments.

Envirotainer has launched the RKNe1, which was designed for the healthcare industry. Constant temperatures are maintained with compressor cooling and electrical heating. The unit features the same type of batteries used in hybrid cars, providing up to 100 hours without recharging, depending on ambient conditions, says Martin Peter, marketing director.

“The RKNe1 is for customers with extreme requirements that want the simplest process possible. All of its temperature-control systems are built redundant. Cooling is automatically adjusted to four different levels, using three compressors. The same principle applies to the heating capacity, where one or two heaters can be switched on, depending on the need,” Peter says. In transit or storage, the container can be connected to a standard ac power outlet and run “like a fridge, with heating,” Peter says.

The unit provides more-precise temperature control because of its cooling and heating functionality, compared to Envirotainer’s t2 active dry ice cooling technology, as dry ice and alkaline batteries are no longer needed. Peter says the RKNe1 meets or exceeds shipping parameters defined by the pharmacy community. The unit holds temperatures inside the container to ± 3° from a set point of 5°C, and ± 5° at a set temperature of 20°C. At extreme ambient temperatures of –10° to +30°C, it runs without recharging for 38 hours, exceeding the expected 30-hour parameter for those conditions, says Peter.

AcuTemp’s AcuTemp RKN Thermal Pallet Shipper is launching in 2006. It employs the company’s ThermoCor high-performance insulation, which is used in its VaxiCool and HemaCool mobile refrigerators and freezers.

“The RKN is based on the HemaCool platform, taking the same technology and applying it to a pallet-sized unit,” says Chris Meyer, senior director of ThermoCor. The battery pack maintains temperatures for at least 72 hours before requiring recharging. Temperatures are held within ±2°C from a set point of 4°C for refrigeration. Batteries can be recharged from any external power source, including grid and solar.

Employing vacuum insulation panels and urethane, Cold Chain Technologies’ va-Q-tainer holds temperatures for 96 hours in year-round conditions.

High-performance insulation provides energy savings and limits temperature swings. “In normal refrigeration, the hysteresis is pronounced. Temperatures will drift up or down several degrees from the set point. We maintain tighter control, allowing a variation of only two degrees on each side with the RKN,” says Meyer.

Besides extending battery life, one of the major benefits of incorporating ThermoCor in the RKN is extended hold time if batteries expire and no power source is readily available. “The amount of time it takes for the ambient temperature and the temperature inside the box to equalize is significantly increased,” Meyer says.

“We have used our expertise in joining technologies to guard against mechanical failure. The compressor-driven system we use is designed for mobile operations,” says Meyer. In temperature monitoring and reporting, a visual screen shows average temperatures from multiple locations inside. Profiles can be downloaded to a PC or handheld computer.

AcuTemp’s VaxiCool and HemaCool units also use battery-powered condensers to generate cold air. VaxiCool is used by county health departments for vaccine storage and transport in their immunization programs, and by the U.S. Army for transport of critical vaccines. “We are filling a large order right now with the army for HemaCool units for transporting blood supplies,” says AcuTemp’s Meyer.

Health departments and pharmaceutical companies typically employ the units for refrigeration at headquarters and use passive transport boxes for shipping smaller quantities to the point of use, says Meyer.

CONSIDERING COSTS

How will these new active-container systems stack up in the marketplace?

“The thermal capacity of these systems is a strong point. But these are heavily niched products. Many of these programs are based on renting these containers and have specific transport lanes or carriers associated with leased shippers,” says Hingle.

“They are addressing the pharmaceutical industry’s requirements for keeping products within a very narrow temperature range. But the industry won’t use these without some qualification of their own temperature environments,” O’Donnell says.

“Acceptance will be slow and guarded. In addition, lane segment availability is still an issue. There is great application if they can get enough of them around to where customers need them,” he adds.

Total costs have to be considered. Along with the leasing charge, users of active shippers have faced costs including container pickup and return charges and battery replacement, says O’Donnell.

Closed-loop reusable solutions can save money in active or passive uses. But “closed-loop systems represent only a small percentage of applications. Active containers that are shipped back empty can be a very expensive proposition. Disposability is less costly and often makes more sense,” says Hingle.

Derifield says that Envirocooler’s pallet system is 30 to 40% less costly than the one-time charge of a leased container per unit shipped. And “if packaging is robust enough, you can put together a requalification program and save even more,” he says.

“With our frozen–gel pack–only BioSphere, our customers save with increased product load, fast pack-outs, and no hazardous freight fees,” he adds.
But Envirotainer’s Peter counters that: “If you consider total cost, including all cost elements of a shipment, active temperature-controlled systems have the advantage that they can take larger volumes at lower cost per unit shipped.

“No additional complex packaging is required, and controls can be set to amend to external influences, such as delays in shipment and ambient temperature changes. Reusable systems require no investment, and they are environmentally friendly, since there is no waste,” he continues.

Peter notes that 75% of container shipments are used for return business and that Envirotainer provides one-way leases in any case. And Envirotainer covers the cost when empty containers have to be repositioned, he says.

Peter notes that active systems now account for 15 to 20% of the market.

“Our worldwide maintenance network calibrates and overhauls the units annually. We have found that our trained service providers, including airlines and freight forwarders, recharge the units much more often and longer than is required. So units typically have to run autonomously for only 10 or 12 hours,” Peter says.

One constant is the need to select packaging that is suitable for defined distribution environments and that can conform to the growing body of cold-chain packing guidances and rules.

Europe and Canada have issued requirements for validation, distribution route definition, and temperature monitoring. “Companies have to transport according to label storage conditions, regardless of whether you have stability data to show it can have temperature excursions outside those parameters,” O’Donnell says.

In the United States, the United States Pharmacopoeia last year published an updated version of General Chapter 1079, “Good Storage and Shipping Practices,” for cold-chain storage and distribution. Under the auspices of the Parenteral Drug Association, the Pharma Cold Chain Distribution Group issued Technical Report #39 Cold Chain Guidance for Medicinal Products: Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment, and they are currently working on a master validation document describing how tests should be performed and documented, says O’Donnell.

“Companies have had very little understanding of what their transportation routes look like. They are realizing that has to change, if they are to meet standards and remain competitive,” O’Donnell says.