- THE MAGAZINE
One year ago, the pharmaceutical industry was buzzing about controlled room temperature monitoring (CRT). That is still a hot topic in the cold chain environment. At the same time, routine (2° to 8°C) cold chain needs are expanding. It is not just the pharmaceutical industry that is affected, either. Medical devices with chemical or biological reagents and all sorts of food are coming under increasing regulatory scrutiny. Even the aviation industry ships certain components — like rivets — at controlled temperatures of minus 40°C.
To meet these needs, logistics providers are stepping up to ensure they have the necessary infrastructure. This means new temperature control products and services are being rolled out and new controlled-temperature facilities are being built throughout the world.
According to the UPS Pain in the (Supply) Chain survey, released in September 2013, 35 percent of respondents said cold chain requirements are driving costs. “That’s because of the increasing numbers of emerging markets, which adds pressures to planning,” says Susan Li, marketing manager for Temperature True, UPS’s air freight service specifically designed to safeguard temperature-sensitive shipments. “As a shipper, you must add a solution to mitigate the risks.” That entails working closely with the carrier through quality agreements, and gaining insights into qualified packaging to reduce damage rates.
The CRT Curveball
The increasing interest in cold chain logistics “threw some curve balls to the logistics industry,” says David Bang, CEO of LifeConEx, DHL’s life sciences cold chain logistics subsidiary. The infrastructure was in place to provide cold chain services for 2° to 8°C and for frozen shipments, but the facilities were unprepared for CRT requirements. (Requirements are contained in the United States Pharmaceutical Convention — USP 797.) Therefore, the world’s leading logistics providers have spent the past few years adding those facilities in a growing list of markets. DHL was among the leaders, building out facilities in growing markets.
For example, globally, “It’s hard to find pharmaceutical grade environments at the airports,” Bang says. That is particularly true in emerging markets. India, for example, has a strong manufacturing base for generic drugs that are shipped throughout Asia, and a growing market for North American and European drugs. Although the airports of Bangalore and Mumbai are familiar with cold storage, CRT was not available.
Indian and Chinese cold chain facilities are particularly important because of the raw materials they supply for drug manufacturers throughout the world. The challenge is to maintain temperature, identify the appropriate packaging and to monitor it to spot trends in shipments all the way down to the packaging level, Bang says. Therefore, shippers and carriers can identify areas needing more attention. “The cold chain’s becoming more sophisticated. Having robust packaging was previously enough. Now regulators want proof.”
CRT — or ambient temperature — eases transportation in some regards, but “controlled” is the operative word. According to the U.S. Food and Drug Administration (FDA), CRT is thermostatically controlled to maintain temperatures between 20° and 25°C, and allows temperature excursions between 15° and 30°C.
American Airlines Cargo continues to expand its CRT offerings. “We just added a new larger (1,250 square foot) CRT facility at JFK airport. “This is a significant point for European shipments and is in the middle of what could be called the pharmaceutical corridor,” Tom Grubb, manager of cold chain strategy, says. It also recently gained approval for a similar facility in London. He predicts it will be completed around the end of January 2014.
In the new cold chain, all the components must work together. “Packaging must be robust, whether it’s hard shell or a cargo box with insulated materials. Handling facilities must be able to store cargo in the proper conditions. Then, there’s the data component,” Bang adds.
In the pharmaceutical industry, the driving force behind the cold chain is the explosion of large molecule drugs, which tend to be biological rather than chemical compositions. The Irish market research firm IMARC Group predicts the healthcare cold chain logistic services market will grow from $6.7 billion in 2013 to nearly $10.7 billion by 2017.
The key reason, as Robin Hooker, director of UPS’s global strategy healthcare logistics, notes, is that “Pharma is moving to a biopharma platform that will expand faster than traditional pharmaceuticals. By 2016, eight of the top 10 selling drugs, 27 of the top 50 drugs sold, will require some type of cold chain support.
“Patent expirations are putting downward pressure on pharmaceutical revenue streams, so we must bring more solutions to the table to help manufacturers economize,” Hooker says. PharmaPort 360 is an active container that heats or cools contents to maintain temperatures within a specified range. This was used with Centers for Disease Control (CDC) vaccine shipments. There also are solutions for lower-cost products. “We are segmenting the cold chain into three tiers,” he says. One of those segments is ambient temperature. “We’re in discussions with manufacturers about their ambient temperature needs.” UPS also is evaluating its controlled temperature network, with expansion in mind.
Cold chain shipping extends to active pharmaceutical ingredients — the raw materials — too. “Bulk is up,” Bang says, because improperly stored raw ingredients can compromise the safety and efficacy of finished products. Although 2° to 8°C comprises 70 percent of the global cold chain volume, controlled room temperature is becoming more popular. This requirement is driven by the need for more consumer-friendly temperature requirements, particularly as pharmaceutical companies supply medicines to developing nations that often lack reliable, consistent electricity and refrigeration.
Food Cold Chain
The British research firm Companies and Markets estimates the value of the global food cold chain will surge from $75.57 billion in 2011 to approximately $157.14 billion in 2017.
At Intelleflex, a provider of on-demand, data visibility solutions for the cold supply chain and asset management, “We’re seeing more focus on food quality and food safety,” says Peter Mehring, CEO. “The level of interest from grocers and quick service restaurants has surged in the past year.” The issue is fueled by concerns about food safety and about waste.
“There also are a number of studies attributing 30 to 50 percent of waste of harvest produce, seafood and meat throughout the supply chain,” Mehring says. The “cut-to-cool” stage is particularly important. “Every hour produce spends at ambient temperature reduces approximately one day of shelf life. To extend shelf life, produce should be immediately cooled, but often it isn’t done early enough, or properly. In the United States, growers have moved cooling to the field, but in other nations produce may take four hours to reach a pack house for cooling.”
At the pack house, pre-cooling becomes the bottleneck. “You need to look at core temperature,” Mehring stresses. Typically, fruit is loaded together and covered. It is treated uniformly. The problem is that the cartons arrive with different amounts of thermal energy, so some need more cooling time than others.
“The coolers in the trailers and containers are only strong enough to maintain cooled products — not to actually chill it,” Mehring points out. “Therefore, it starts to warm in the refrigerated trucks. Small errors — like pre-chilling only to 40°F — accumulate and can reduce shelf life by 30 percent. The surprise occurs when drivers haul freight a few days and find the food is spoiled because it was handled improperly at the early stages.”
The major regulations in the food industry are follow-ons to the Food Safety Modernization Act (FSMA). For example, “Prepared salads are very sensitive to microbial growth,” Mehring says. “The new FSMA standard, therefore, requires documentation that they have been maintained less than 40°F.” He predicts a lot more FDA requirements to be released in 2014. “There’s a lot of discussion about this, and display cases built in ways to monitor temperature.” Interest is growing in monitoring temperature between the distribution centers and the retailers, which normally isn’t done.
For pharmaceuticals, new Good Distribution Practices (GDP) guidelines were introduced in Europe in 2013 that specify the same temperature for products regardless of whether they are being moved or stored. Brazil has similar requirements, based upon the claims on the label rather than on range allowed by the laboratory. Carriers report, anecdotally, that Brazilian customs authorities require temperature data for many pharmaceutical products entering the country. Products with temperature excursions may be refused.
Many receivers and regulatory agencies “require wholesalers to prove goods were properly handled,” Li says. Also, anecdotally, “We see more clinical trials being monitored. Therefore, customers are using low-cost temperature indicators to provide peace of mind.”
“Throughout the world, GDP guidelines are becoming more focused,” Grubb says. “On top of that, South American countries, in particular, are increasing customs regulations, and the International Air Transport Association’s Time and Temperature Task Force is working with everyone to understand the issues,” and move the industry toward regulatory harmonization.
DHL’s Bang says the new regulations give it a competitive advantage. “There are always new regulations. The EU GDP regulations that took effect in September 2013 will be copied into individual country regulations. The stricter regulations increase customers’ demand for higher level so compliance from logistics companies and, in some areas, we’re the only provider (that deliver that level of regulatory assurance.)”
The increasing use of the cold chain is manifesting in new services based upon increased connectivity. For example, Li says, “Connectivity of data between manufacturers and logistics providers is increasing.” This enhances visibility into the supply chain for in transit inventory. For the pharmaceutical industry, this increased integration is a major step toward ensuring safety. “At our facilities, we have a banner that reads: ‘It’s a patient, not a package.’”
Cold chain awareness is increasing and is helping drive home delivery, Mehring says. For example, “Amazon Fresh grocery delivery and similar services will force traditional retailers to step up.” The challenge, he explains, is that home delivery consumers must trust retailers to choose their produce for them. Earning that trust requires a freshness guarantee. Last June, Wal-Mart Stores Inc., the nation’s largest grocer and seller of produce, announced a 100 percent money-back guarantee if consumers are not happy with their produce for any reason. Walmart also is training its managers and employees about food handling, among other changes to ensure freshness.
Data monitors are becoming increasingly popular, particularly for air freight, because of the high value of the cargo and because of export controls, Li says. But, Hooker adds, the technology needs to improve so that data loggers can be recovered more easily. Sometimes receivers have the best intentions but, even with return envelopes, the loggers sit on desks or are thrown away.” That is a particular problem for small package delivery, he says.
In contrast, Hooker says, “On the freight side, containers are easily outfitted with data loggers,” that are managed with the container. “Some passive temperature indicators do a decent job, but they often need to be handled carefully before being deployed.”
Intelleflex launched its Zest real time temperature alert monitoring system last April, which enables handlers to take corrective action. “We focus on providing actionable information and real time alerts at loading docks or cold storage facilities, where there are workers,” Mehring says. “Zest pulls all data and works like social networking, so it knows who’s at which location and whom to notify for temperature excursions.”
“Not all insulated packaging lasts,” Bang says. Many packaging solutions can maintain temperature five or six days at the most. When everything goes smoothly, that may be sufficient, but when there are delays, the contents may be at risk. DHL’s new Thermonet addresses this challenge. Thermonet integrates proactive monitoring and intervention with RFID SmartSensor technology. SmartSensor monitors the ambient temperature throughout the shipment. An optional service monitors the near-product temperature of the items being shipped. Data uploads automatically over DHL’s LifeTrack IT platform.
Based upon that data, when temperature excursions are imminent, Bang says, “We can unload items from the packaging, move then into refrigerated trucks and return the insulated container. This is one of our biggest advantages. It gives customers options they normally wouldn’t have.”
American Airlines Cargo recently introduced its FlightSafe monitoring solution. Shippers can deploy this data logger on a per-shipment basis, Grubb says. It tracks nine parameters, including light, temperature, humidity, shock and vibration. It can even be used for geofencing. FlightSafe can be used without long term contracts. “Clients can order it when they book transportation. It is shipped to their facility with operational instructions. At the end of the shipment, the receiver slips it back into an envelope and returns to the warehouse for reconditioning and storage.
“The customer does the monitoring,” Grubb points out. American Airlines Cargo can take preventive measures upon the client’s instructions. “That’s part of our standard contingency processing.”
UPS is expanding its air freight capability to offer various levels of cold chain services, including small package proactive responses. Last summer, UPS introduced Proactive Response Secure, which combines insurance with proactive monitoring and intervention. The product is based on time — not temperature — monitoring. As Mark Robinson, VP, UPS Capital, explains: “If high value products don’t arrive on time, the contents may become a loss, with or without physical damage to the package. That can be costly, so we developed a product that combines tracking with the ability to take action.”
Currently, UPS Proactive Response Secure is available in the U.S. and Puerto Rico and will soon be added to Europe. “We’re planning to offer this in Asia during the second half of the year. Locations are based upon the ability of UPS to interdict and reroute packages in transit. UPS Capital takes the risk of loss and actively manages these packages, paying for any additional steps to ensure the package arrives in time,” Robinson explains. That includes shipping with a faster level of service, returning it to customers or putting it in a temperature-controlled environment. Insurance is integrated.
Additionally, UPS has undertaken detailed studies to understand the UPS network baselines for temperature, humidity, vibration and shock, Li says. “This is important for package design, especially for sensitive products like vaccines and oncology drugs.” With that information, clients “can develop good risk mitigation plans to protect their products. We began this in 2008 and constantly check the network. Results correlated with the national weather, and the results depend on the mode. Each carrier is different,” she says.
The cold chain is growing tremendously throughout the world, and will continue to do so for the foreseeable future. This growth is driven by new products that require temperature control, new regulations that require data loggers or indicators to ensure product safety, and the growth of a middle class that can afford these new medicines and foods grown and shipped throughout the world.