By Fred Olds
For the pharma industry, the challenges of cold chain transport continue to grow. The consequence of error or omission can be serious for patient safety — and company financial viability.
Technology has made both the health products and the capability to transport and monitor them in transit more complex. Mark Mohr, manager of product development and specialty sales for Continental Airlines, says logisticians welcome new technology to improve efficiency, but are alert for unintended consequences. For instance, to reduce weight and increase fuel economy, composite material is replacing aluminum in new airframes. Aluminum transfers heat better than composite by a factor of 20% to 200%. This change in material could result in a critical temperature difference that affects the efficacy of pharmaceuticals in transit with his airline. Pharma has to rely on transportation service providers to resolve questions like this and ship products under the strict conditions needed to preserve efficacy. The ultimate responsibility, however, still falls on the pharma company.
“There is never enough planning,” says Bob Gahan, VP Global Sales – Healthcare for DB Schenker Inc., and planning needs to start as early as possible. Each shipment is a singular experience regardless of how often it’s been done before. Gahan says unexpected events have a way of nudging critical steps in plans. During his daughter’s spring break in April 2010, Gahan had planned time with his family. Unexpectedly, much of European airspace was closed by the eruption of Mount Eyjafjallajökull in Iceland. He recalls using contingency plans to reroute shipments on his cell phone while attending his daughter’s lacrosse games.
At the Boston Marathon, he received a call to secure an urgent delivery of blood product to Europe. Passenger flights were not operating. The only option was to charter a 767 all-cargo freighter. Spain was open, but overburdened with other rerouting. Late that evening after a day of coordination between the United States and Europe, the manufacturer and Gahan agreed on an alternative option. Leipzig was open, and the manufacturer had enough resources there to arrange receipt of the product. Working with governmental agencies, manufacturer reps obtained landing rights for Leipzig in 6 hours under a “medical emergency,” normally a five-day process.
Plans that define communication and contingency options between the manufacturer and transport service provider are critical. The manufacturer can identify supported alternate sites for delivery; the transport service provider develops contingency plans to deliver to those locations.
“In planning pharmaceutical cold chain shipments, it’s all about the timing,” says Gahan. “One of the biggest things people get wrong is they think about what day they’re ready to ship. Really, in the cold chain world, you have to think about when the destination can receive it.” You will want to avoid Rio de Janeiro during the height of Carnival, or a late Friday arrival in a country where customs routinely closes early for the weekend. You do not want your shipment sitting on the tarmac or in an airport holding facility for days risking temperature excursions. The saying among experts is, “Freight at rest is freight at risk.” Determine the day the shipment can clear customs, get to receiving, and return to cold chain storage. Plan backward from that date to determine the outbound ship date.
Global logistics providers have developed intricate protocols for their operations. Their customers need to follow that lead. Gahan recommends approaching the process by “attaching yourself to the package.” Envision who will pick up the package at each step, who will sign for it, where will it move, and where will it sit. Map out the process in a written document or spreadsheet. This becomes the foundation of your quality and service level agreements with your provider. Designate who will be following the shipment and who will coordinate with the shipper at each step. Importantly, appoint a person with authority to deal with contingencies 24/7, and know who is doing that at the transportation service provider.
Mohr emphasizes the need to involve everyone in transportation decisions early. Everyone involved in the supply chain will need to know the parameters for stability, the size of the shipment, security, and dates. Lead time should be in weeks and months, not days and weeks. As the degree of shipment difficulty increases, so should lead time.
A final imperative is a site visit, says Karl Kussow, manager of quality at FedEx Custom Critical. Manufacturers should inspect transportation operations to ensure the provider can meet safety regulations and the manufacturer’s requirements for the shipment. It’s due diligence.
There are two early decisions — whom to ship with and what to ship it in. While this is stating the obvious, the decisions are not. FDA cGMP requires manufacturers to keep source materials and pharmaceuticals within safety parameters from production to distribution. Any undocumented period of physical control of a shipment (e.g. temperature excursion) could render them adulterated due to failure to follow cGMP. Manufacturers need a transportation partner that understands and has the capacity to operate under cGMP and provide cold chain security end to end.
“It’s important to be able to prove pedigree,” says Kussow. “The FDA might want to know exactly where a compound has been and how it was monitored if safety or efficacy issues arise. Similarly, customs could hold or refuse a shipment altogether if there are discrepancies in documentation.” So manufacturers should choose a shipper that has door-to-door experience with the transportation and surveillance of cargo, including both security and environmental monitoring. Kussow says technology is providing, and will provide more options, including real-time data such as GPS location, temperature, and time in transit.
The FDA, professional organizations, and other agencies establish cGMP, and some of them carry the weight of law. The “c” for “current” in cGMP can be particularly challenging. Technology has a short shelf life, and “current” may be redefined or updated.
Consider electronic signatures used to track many shipments. The FDA announced in July 2010 it would begin “a series of inspections in an effort to evaluate industry’s compliance and understanding of Part 11” of 21 CFR, which sets requirements for signatures. The FDA provided guidance for minimum security and auditing standards, but manufacturers must prove compliance. As technology upgrades to newer, more secure programs, you need to know what the new “current” is.
Levels of security and monitoring have increasing costs. The choices form a rubric of time, temperature, security, and budget. Kussow says companies need to develop a risk-cost benefit proposition. A new rare experimental compound might be worth greater levels of security than a small load of OTC products. It’s a decision shipping companies are very capable of assisting manufacturers with.
Begin the selection of packaging by determining the parameters of size, temperature, time, and distance. Consider the shipment of a biological from Boston that requires a storage temperature range between 2 degrees and 8 degrees Centigrade and protection from light. Going nonstop to a wholesale warehouse in Alpharetta, GA, the product might be shipped using insulated company packaging in a controlled climate vehicle. A shipment to a UN refuge center in the Sudan requires considerations on an exponentially different scale.
Packaging choices are generally divided between active and passive environmental control. In active packaging, cooling the temperature is controlled by an electrical or mechanical device usually powered by batteries. Active systems are commonly sturdy, hard-sided, prebuilt containers, often used for larger pallet-sized shipments. These systems offer reliable performance and the convenience of thermostatic temperature control. A setting is dialed in and the temperature is maintained mechanically. The units have been designed to fit truck and air cargo holds and are reusable with little waste or environmental concern. Some considerations for active systems are cost, battery life, and size. Active systems are generally more costly, and require monitoring to ensure batteries are still strong. Active systems tend to be larger and offer fewer options in size. This could result in paying for a larger footprint onboard than the shipment requires or reducing the size of a shipment to fit the container.
Passive units utilize insulation and phase-change material. For phase-change material, think gel pack, then expand your conceptualization. These are substances that have a high heat of fusion. In simplified terms, as they melt or solidify over time, they produce or absorb energy which will either heat or cool their surroundings. These compounds have been engineered to change at predictable rates.
Companies use phase-change material to produce a package that can be qualified to keep contents within specified limits for specific time periods. The advantages of passive shippers are lower cost and more flexibility in size. With new designs, less space is required to provide the cold chain requirements, thus reducing costs. Passive shippers provide consistent control even when the boxes are transferred from one conveyance to another, since they are never opened. The downsides are time limits on the ability of the materials to maintain containers within range. Passive units are not regularly designed for large pallet-size shipments. Although recyclable and biodegradable materials are available, most passive packaging is single use and results in waste that has to be discarded.
Kussow offers some advice when choosing. First, make sure the packaging is qualified for the desired purpose. That is, get assurances that the delivery package has been tested to keep the contents:
Second, make sure everyone in the chain is trained to handle the packaging used. Transferring a package from one hand to another creates a critical control point for possible error. A passive shipper can inadvertently be placed in a refrigerator by someone thinking it will keep the shipment better protected. Instead, some phase-change material is designed for specific storage temperatures and might actually freeze at lower temps. In actively cooled trucks or containers, doors could be left open, exposing products to ambient air.
The Future And Creative Solutions
The future holds several challenges for pharma. Healthcare profits will be squeezed by expiring patents, payments to the government for Medicare Part D coverage, lower reimbursement by Medicare, unknown changes in federal law, and unintended consequences from all of these.
With the expiry of blockbuster patents generic companies will pick up multibillion dollar products. They and their shipping service providers will have to figure out how to ship the same products from more distant ports with fewer financial resources. Risk benefit equations will be reevaluated.
Every challenge, though, offers opportunity. Expect the desire to improve healthcare worldwide to have sustained humanitarian impetus. Pharma is being asked to provide more medications to treat diseases in underdeveloped countries. The demand to maintain the safety of those products in the process is a logistical challenge. With a little time and planning Mohr says, “Almost any shipment to anywhere is possible, but sometimes it takes creative solutions.” He cites the Camel Fridge System developed by NAPS Systems in Oy, Finland. The WHO needed a delivery device to get vaccines to desolate desert areas around the world. NAPS devised a refrigerating container powered by solar cells attached to the back of a camel. It’s an iconic union of centuries different technologies.
Transportation service providers and packagers devise solutions through new and old technology. They offer a complete line of compliant cold chain options up to individually chartered high security single client vehicles. In the increasing need for cold chain in pharma, companies will need to plan carefully with providers. Final responsibility falls on the manufacturer to make the difficult decision to balance patient safety with company resources.