Understanding Risks in Pharmaceutical Shipping

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Shipping of pharmaceutical drug products­-which may involve long, complex routes and require temperature-controlled environments-can be challenging. "Temperature excursions, customs delays, packaging breakdowns, incorrect shipping, and packing choice are all risks inherent in today’s global logistics market," notes Sue Lee, global technical portfolio manager for World Courier. The shipping process is crucial; indeed, "Lives may depend on a drug making it safely from origin to destination, within temperature range, and on-time," notes Carl Asmus, vice-president of supply chain solutions and market development at FedEx.

Pharmaceutical Technology spoke with Lee; Asmus; Brian Kohr, president and CEO of CSafe, a cold-chain solutions provider; and Wanis Kabbaj, marketing director, UPS healthcare strategy, about these risks and the shipping solutions available to mitigate them.   

Challenges

PharmTech: What type of bio/pharmaceutical products are the most challenging to ship, and what solutions can be used?

Lee (World Courier): As the industry moves from ‘blockbuster’ products to personalized medicine, especially customized treatments for patients with rare diseases, expensive medications with low volume and high value will become the shipping norm. These shipments present extreme challenges in their intrinsic value. At the same time, we’ve seen a significant jump in the number of clinical trials conducted in emerging markets, where transport and storage of investigational medical products and patient samples can present a host of daily and diverse obstacles.

Solutions for these shipments can be as unique as the shipments themselves. The expertise and control offered by a knowledgeable shipping partner-in everything from choosing the best system for the route and correct preconditioning of phase-change materials, to correctly configuring and positioning temperature monitors-are invaluable. The right packaging, following the right route, and the right expertise in each local market is crucial to providing a successful, unbroken supply chain for these potentially life-saving therapies.

The recent partnership of World Courier with Medical Research Network (MRN) seeks to address many of the challenges of global clinical trials by creating a solution that combines product transport, storage, and nursing services in a secure, transparent solution. As emphasis shifts to patient-centric medicine, the question is not just getting a product from point A to point B, it’s also what happens to the product once it gets to point B.

Lastly, new therapies are bringing a broad range of temperature needs to the supply chain. For example, there are now therapies that require storage at body temperature, and by necessity they will require a different approach compared to the traditional cold chain. Humidity, light, and even movement-sensitivity (i.e., products that cannot be jarred during shipment) might be factored into shipping concerns. All combined, it’s safe to say that as products themselves grow more complex, more diverse, and more specialized, supply-chain technologies and processes must become more advanced to support individual shipper needs.

Kabbaj (UPS): New, large-molecule, biologic treatments are increasing. These drugs are typically less stable than small-molecule drugs, making them more challenging to ship and requiring a highly customized solution. A high-end cold-chain solution using active containers and an extensive visibility control-tower solution is key.

In addition, high-value drugs that are shipped in a small-package network require acute attention to detail. These shipments travel as one package among others, but because of their value we need to make sure they are shipped to the right person and on time. In this case, properly engineered passive packaging is key. Appropriate packaging combined with proactive monitoring and intervention adds layers of protection.

Controlled substances like oxycodone present potential security risks and become challenging to ship. To mitigate these risks, we use real-time monitoring devices that track shipments constantly by using geo-fencing. Geo-fencing allows UPS to predetermine a safe route and define an acceptable digression distance for the drug to mitigate diversion and theft.

Any biomaterial that requires cryogenic temperatures (-150 °C), such as clinical trials or biologic materials (e.g., blood, tissue, reproductive material), presents challenges within the supply chain. UPS works with a cryogenic container that is designed for our network and holds the temperature at -150 °C for at least 10 days. Visibility solutions help customers keep an eye on these shipments in real-time.

Asmus (FedEx): Complex pharmaceutical trials offer many challenges, from security to temperature control. For example, FedEx recently worked with Clinical Supplies Management on a trial involving medication that was prepared in a laboratory, shipped overnight throughout the United States to be used within 48 hours, and maintained at 2-8 °C. Tracking and monitoring devices enabled verification of location and temperature control.

Temperature controlPharmTech: What are the most concerning aspects of temperature control for the shipping service provider? For the customer?

Kohr (CSafe): Challenges are similar for both a service provider and their customers: finding a solution that performs; meets regulatory obligations; meets any other objectives, such as sustainability; and has an acceptable cost.

Kabbaj (UPS): For the shipping service providers, there are three concerning aspects of temperature control: hand-offs, customs, and unexpected events. When a product is transported from origin to destination, the chain of custody can become complicated and long as the product passes among the shipper, the airline, the forwarder, and eventually to the end customer. All of these changes in custody are potential areas of concern as the risk for temperature deviation increases. As supply chains become longer and cross multiple borders, customs is a key area of concern for providers. Some countries outside of North America and Europe have much slower customs processes where goods may be held up in transit longer than expected. Finally, unexpected events, including mechanical issues as well as low probability, high-risk events, such as labor strikes, extreme weather, volcano eruptions, and earthquakes, can have strong consequences on the integrity of temperature-sensitive shipments. Providers must have a firm hold on the amount of risk they are willing to accept and contingency plans in place to react or mitigate any risk associated with unplanned events.

For the customer, there are two main temperature-control concerns: cost and quality. Customers must find the right tradeoff between cost and the quality of their temperature integrity. At a high cost you can mitigate most risk, but is that something you want or need? How do you get to a point where the cost is competitive, but quality and risk mitigation are high? Contracting the right quality agreement with providers and ensuring it is respected throughout the entire supply chain is important. If the provider is using third-party vendors, how do you make sure that the service level you were sold is being taken into consideration at every step of the supply chain?  Outline the level of monitoring, auditing, and visibility that is expected and formalize an agreement to make sure it gets done.

PharmTech: How do you address shipping requests to areas that do not have facilities for temperature control?

Asmus (FedEx): Packaging and transportation solutions that can maintain temperature integrity and also eliminate unnecessary costs are key. For example, thermal blankets for pallets are available to offer protection against sunlight, humidity, and tarmac heat.

Lee (World Courier): Controlling the external temperature will always remain the best possible option, whether using temperature-control offerings from the airlines, certified airports, or over-packing the whole consignment with an active unit. However, these methods are not always a viable option due to lack of infrastructure at the destination. Manufacturers need to invest in packaging that is independent of the physical facilities available over the duration of the shipment, allowing the shipment temperature to remain stable even when storage conditions differ from expectation.

It is important to have a knowledgeable team on the ground at every step. A reliable partner that can be present during pickup and delivery will allow for greater control over the product’s shipping life. All challenges and risks should be clearly identified in advance of the product being shipped, so that the shipping partner can work to alleviate issues early and often. This approach is also hard wired into regulatory requirements, including the European Union’s good distribution practice guidelines.

Kabbaj (UPS): Most of the global areas where UPS operates do not have temperature controls. A key way to address requests in these areas is through packaging and monitoring services. Cold-chain packaging will protect the product from temperature variations throughout the trip. Active, passive, and semi-active packaging solutions can be considered in conjunction with the known temperature conditions of the journey. Once proper packaging is defined, the compatible mode of transportation can be determined.

Passive packaging may be protective for a certain amount of hours, so you must ensure a timely delivery before the pack-out expires. For active packaging, you need to make sure that the temperature is maintained throughout the supply chain, which can be done by implementing processes and training employees on how to handle those active-packaging solutions when they need to handle or intervene. Risk-management solutions must be in place for handling temperature-sensitive freight. A solution that proactively determines when a shipment is likely to be distressed or in jeopardy, an improved track-and-trace solution for real-time risk management, and capabilities to act on the data to expedite or reroute the shipment are all important components of a risk-management solution.

It is important to note that the idea of temperature-controlled facilities providing full coverage throughout the supply chain is misleading. No full chain is completely temperature-controlled without appropriate packaging. When product in passive packaging leaves the controlled premise of a facility, truck, or airplane during handoff, it is in danger of temperature excursion if not delivered by the time the packaging expires.

Kohr (CSafe): When we designed our active packaging unit, we created a solution that did not require refrigerated trucking, refrigerated warehousing, re-icing or any other human intervention other than moving the product from A to Z. If there are no temperature-control facilities at Z and the container was going to sit for a period of time, the container is designed to simply plug into a wall outlet.

Transportation modePharmTech: Identifying and mitigating risk is crucial. Do some risks depend upon the mode of transportation, and what factors go into choosing transportation mode?

Kabbaj (UPS): Risk, particularly for temperature control, absolutely depends on the mode of transportation. Typically, the faster and more integrated the mode, the lower the risk. For example, if you ship a small package by air with an integrator like UPS you are only dealing with one vendor that controls all the assets and the network that your product is transiting through, and you are transporting the product quickly. In this instance the handoffs and exposure to the outside environment are limited, so there is lower risk.

On the other hand, a ground transportation shipment over a long distance and through multiple transportation providers and modes (i.e., truck and rail) is subject to more risk. The mode is much slower than air and the exposure to external temperature variations increases during handoffs.

Cost, temperature, and timing are all important in selecting the appropriate mode of transportation for a temperature-sensitive shipment. It is important for shippers to leverage extensive logistics portfolios with global air, ocean, and freight services. These should give customers the flexibility to meet specific cargo size and timing needs while maximizing routing, transit times, and cost management.

Kohr (CSafe): Each mode of transportation (air, ocean, and ground) provides different benefits and risks. The risks include cost, likelihood of quality issues, liability, and level of capital deployed due to inventory in transit. Not every product or routing is suited for the same supply-chain solution or for every season. Companies that exercise and deploy various options are leading the way. Everyone wants simplicity, but simplicity may bring increased costs and increased risk. An active temperature-control container, for example, all but eliminates the human and environmental elements, but may not be the right supply-chain option from a cost perspective. There is always that crucial balance of cost versus risk.

Asmus (FedEx): Transportation mode is only one element of the decision; it is important to determine the ideal transportation mode for their shipments based on many factors, such as service level and price point.

Lee (World Courier): As shipping and packing technology advances, the goal is to reduce the inherent risks associated with the mode of transportation. Experts agree the shipper should consider choosing packaging that is independent of the supply chain itself, which can keep shipments on-temperature. The question is less about mode of transport, and more about choosing the right packaging for your product and its journey. For example, semi-active packaging solutions usually bode well for shipments that are only going a short distance. However, for longer distances, customers should be looking at passive packaging solutions like phase-change material. Passive packaging allows for more precision and temperature control and maintains product stability over long distances and through extreme climates.

Article DetailsPharmaceutical Technology
Vol. 39, No. 8
Pages: 52-54

Citation: When referring to this article, please cite it as J. Markarian, “Understanding Risks in Pharmaceutical Shipping,” Pharmaceutical Technology39 (8) 2015.