Optimización del control de temperatura para productos biofarmacéuticos
Volker Kirchner comparte su perspectiva sobre las estrategias para seleccionar tecnologías con control de temperatura
Today pharma companies are faced with an ever changing market that includes increased regulatory challenges, globalization, and heightened competition (1). Biopharma companies are rapidly expanding into emerging markets where there are new opportunities for drug development. Conversely, logistics companies must keep up with the demand, ensuring all storage technology is equipped to retain the safety and efficacy of a drug by the time it reaches the end of its journey.
Selecting the appropriate shipping storage system can be a challenge for even the most knowledgeable manufacturers. Choosing a storage system that maintains the integrity of a drug throughout the shipment process is of paramount importance to biopharmaceutical manufacturers looking to bring a drug to market. This is particularly relevant as biopharma companies expand into emerging markets where infrastructure may be lacking, says Susan Li, manager at UPS Temperature True Packaging. According to Li, as travel times increase, companies have to figure out how to keep drugs safe and compliant for a longer period of time and through a greater span of temperatures.
The lack of a proper logistics plan can directly impact the development timeline of a drug, says Mark W. Sawicki, PhD, chief commercial officer, at Cryoport. According to Sawicki, shipping systems that do not maintain the efficacy of a drug can have a direct economic impact on a biopharmaceutical company, leading to the loss of “millions of dollars of API, clinical samples, and underperforming bioanalytical assays.”
Because there is so much at stake, Nadine Siqueland, vice-president of Sales at CSafe Global, says companies are under “tremendous pressure” to deliver their drug to market as quickly and safely as possible. She says using the most robust packaging solutions are imperative to maintaining the compliance of a drug throughout shipment.
But according to Dan Bell, vice-president of Regulatory Compliance and Technical Affairs at Marken, selecting the appropriate storage system is only part of the challenge. Companies must build a fully compliant GMP global network. This should include a logistics partner equipped to handle any challenges a drug might face throughout the supply chain. Several hand-offs throughout the supply chain can lead to numerous opportunities for mishandling. For this reason, “distributors and supply-chain solution providers must be the link in the pharma supply chain to ensure compliance,” he says.
Common considerations for shipping biopharmaceuticals
Changing global regulations mean biopharma companies are facing more stringent guidelines when shipping drugs long distances. Drugs that may have been shipped at ambient temperatures several years ago must now be shipped under controlled levels (2). As a result of stricter regulations, and an increased number of specialty biopharmaceuticals coming to market, logistics providers must invest in more temperature-sensitive storage options.
Volker Kirchner, director of temperature control solutions at World Courier, says the first step in packaging selection is choosing a shipment solution that can accommodate the temperature range of the product and the travel route. “The decision to move forward with an active or passive packaging system should, for the most part, be based on the transport route,” Kirchner says. “For example, passive systems are often better suited for long-distance deliveries through remote or rural areas, where there’s no access to the storage capabilities needed to recharge or maintain an active system.”
Once the appropriate packaging solution has been selected, it is important that the systems are validated to ensure the effectiveness of the storage system. “All equipment should be validated, calibrated, and monitored,” says Bell. Cooling systems must be able to hold their temperature with minimum intervention. Logistics providers must also prepare for emergencies, such as power failures, where a back-up battery or generator can take the place of a more traditional power source. In the event of a fluctuation in temperature, thermometers with alarms are a good option, Bell notes, notifying the shipper that temperatures have reached unsafe levels.
Sawicki agrees all cold-chain storage containers must be validated and have attachment to backup generators and alarms. But, he says, a second consideration companies should recognize is capacity. “Large projects for -20 °C storage may require a cold room; cell lines or infectious material may require segregated cryogenic storage,” Sawicki says. It is also important to consider the condition of the product when it is pulled from storage for shipment. Using technologies such as cold-carts, Sawicki adds, can limit temperature fluctuations in the time period between the storage and shipment of a product.
While temperature is an important consideration, it is not the only component companies should consider. Factors such as shock, vibration, light, and humidity could all have potentially damaging effects on biopharmaceuticals throughout shipment, Li says. To address these issues, she adds, logistics providers should consider including, “specialized packaging, advanced temperature and location monitoring, and in-transit intervention.”
Temperature management in extreme climates
Logistics companies must pay particular attention when routing drugs through extreme temperature conditions. If possible, providers should altogether avoid shipping biopharmaceuticals through these climates, Kirchner advises, particularly if the origin and destination of the product are more temperate. If avoiding extreme temperatures is not possible, there are several options logistics providers have to maintain temperature stability throughout shipment.
Companies should take the time to understand whether or not the selected storage system has been validated to perform effectively under extreme temperatures, says Sawicki. Making a packaging selection based on logistics data such as, “geo-location, lane mapping, and carrier performance,” he added, can better allow companies to select the most appropriate shipping solution for their product.
Another way companies can mitigate risks associated with shipping temperature sensitive materials includes selecting a temperature tracking device that can monitor the temperature of a load throughout shipment. According to Bell, while data loggers are the primary method for tracking in-transit temperature, these loggers only allow the user to retrieve temperature data at the end of the journey. More recently, he says, real-time GPS tracking devices are coming into play, allowing for the temperature of a load to be read consistently throughout its journey. This technology, Bell continued, sends alerts if there is a temperature fluctuation, the shipment is going out of specification, or the product is exposed to harmful temperature levels.
Many airlines also provide built-in temperature options for longer distance shipments, says Siqueland. Mobile cooling systems and in-airport refrigerated warehouses assist in maintaining product quality throughout the supply chain. For extra support, Siqueland notes, the use of active protection systems can track the temperature of the product throughout shipment, allowing for companies to troubleshoot any issues that may occur.
Tracking the temperature of a shipment is important, but ultimately useless, if companies do not have a plan for intervention should the drug reach unsafe temperatures, says Li. “If a company is not able to act upon the insights that data and technology reveal, the technological advancement is worthless,” she says. Contingency plans that assess whether or not the company and logistics provider have the appropriate technology and intervention capability are imperative to mitigating risks associated with long distance shipping, Li added.
Although regulations are becoming more strict, logistics providers are developing new technologies to enhance safety and product quality throughout the supply chain. Nearly a decade ago, companies switched from shipping drugs in containers with Styrofoam box interiors to vacuum panels, Kirchner says. “These panels significantly reduced transportation costs, while providing the same high-level thermal protection. Since then, advances in technology have enabled transport agencies to replace the hard exterior—often composed of aluminum and plywood—with a composite layer that’s just as robust and much lighter. The new packaging system, which still provides the same high-level of thermal and physical protection, can significantly reduce transport costs,” he said. The majority of advancements have been made to passive systems, he added, because many active systems already control temperature through outside manipulation.
Storage systems that are equipped with options for both heating, cooling, and advanced insulation can now provide effective protection for several months with a continuous power source, Siqueland says. For shorter distances, insulation along with new phase-change materials can provide ample protection for biopharmaceuticals, she added, as long as there are contingency plans in place.
New cloud-based systems develop data chains and can track the shipment history of a specific product until it is received by the patient, Sawicki says. These systems improve integrity for clinical trials and post-market surveillance of drugs. Cloud-based solutions ensure transparency throughout the supply chain, he added, automating much of the shipment tracking, data monitoring, and data-management involved in logistics.
According to Bell, the most significant advancements in supply chain storage systems involve “GPS tracking technology, Bluetooth, and radio frequency identification.” These systems are particularly helpful when shipping cell- and gene-based therapies, he says, giving companies the ability to precisely track the location of the product within the storage facility and ensure chain of identity.
As pharma companies increase their biopharmaceutical portfolio, logistics companies will have to develop more innovative storage solutions for global transportation. This includes shipping treatments to patients in more remote locations, as treatments become available and clinical trials begin for diseases such as Zika. Companies will also likely begin to face new challenges as processes become automated. Logistics providers and biopharma companies may find themselves working to increase cyber security surrounding cloud-based data solutions. In an increasingly competitive marketplace, however, it is likely many providers are up for the challenge.