Accelerating Technology Adoption to Track the Cold Chain

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The biopharmaceutical industry is very familiar with cold-chain distribution and has established supply chains for maintaining biologic drugs at the necessary temperature, including the refrigerated temperatures (at 2–8 °C) needed for many vaccines, down to standard freezer temperatures (-20 °C), deep-freeze using dry ice (-70 °C), and even cryogenic temperatures (-150 to -273 °C). Carefully designed and validated packaging, storage, and transportation systems, with sensors measuring temperature excursions, are all available. Distributing authorized COVID-19 vaccines urgently and at large scale, however, is a new challenge, which is being met in part by accelerating adoption of technologies such as GPS-enabled tracking and supply chain visibility systems.

Vaccine cold-chain requirements

At time of publication, Pfizer and BioNTech had received FDA Emergency Use Authorization (EUA), authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA), and authorization from Health Canada for their mRNA-based COVID-19 vaccine and had submitted applications to the European Medicines Agency and other regulatory bodies; the vaccine was on its way to distribution sites. Moderna also received an FDA EUA for its vaccine in December 2020 and began US distribution, and the company’s applications were being reviewed by other regulatory bodies. AstraZeneca was preparing regulatory submissions for its vaccine candidate, AZD1222. These three vaccines have different cold-chain requirements.

Pfizer and BioNTech said that they would ship the frozen vaccine, BNT162b2, directly to the point of vaccination using a just-in-time distribution network by air and ground transportation to get shipments from the manufacturing site to the point of use (POU) in one or two days (1). The vaccine will be shipped in temperature-controlled shippers using dry ice to maintain a temperature of -70 °C ± 10 °C for up to 10 days. The companies said that vaccine administration sites could store the vaccines in ultra-low temperature commercial freezers for six months, refill the shipping containers with dry ice to use them as temporary storage units for 15 days, or store the vaccine at 2–8 °C in a refrigerator for five days. GPS-enabled sensors on the shipping containers will track location and temperature so that Pfizer can proactively identify and prevent potential problems, such as temperature excursions. Pfizer reported that it was running pilot shipments to help refine the delivery plan (2). Test packages were shipped to Rhode Island, Texas, New Mexico, and Tennessee; the four states were chosen to demonstrate a range of immunization infrastructures that could reach individuals in urban and rural settings.

Moderna said its vaccine, mRNA-1273, should be maintained at -20 °C, which is a standard temperature for home or medical freezers, for up to six months (3). The company reported that mRNA-1273 will remain stable at standard refrigerated conditions (2–8 °C) for up to 30 days within the six-month shelf life.

AstraZeneca anticipates its adenovirus-based vaccine will be transported and stored at 2–8 °C (4). This vaccine and others with less stringent temperature requirements would be easier to distribute globally. AstraZeneca and Moderna’s vaccines could use existing vaccine distribution infrastructure. Yet, although Pfizer’s vaccine requires deep-freeze temperatures, the company expressed confidence that its distribution systems, with shipping via its established systems of carriers such as UPS and FedEx, were ready to go.

Container technology

In addition to Pfizer’s purpose-built container for its own vaccines, suppliers of commercial cold-chain containers have modified their systems to address the needs of COVID-19 vaccines.

Pelican BioThermal, for example, introduced a new -35 °C version of its Crēdo Cube container that uses a new type of phase change material (PCM). “PCM is easier to work with than dry ice, and we offer PCM coolants that can achieve -50 to -20 °C,” says Adam Tetz, director of worldwide marketing at Pelican BioThermal. The company also created a pallet-accepting shipper, the Crēdo Cargo, for dry ice. “Dry ice is the only material that can be used to achieve -80 °C. We had to separate the dry ice from the payload itself [using a physical spacer system] to avoid a cold shock that happens when dry ice contacts the payload or payload box,” explains Tetz.

Distribution challenges

The sheer scale of vaccinating the world is certainly a challenge. Availability of equipment (e.g., freezers) and materials (e.g., dry ice) is also a concern, but manufacturers are working to increase production capacity. Air transportation is another potential challenge, especially for vaccines that require deep-frozen temperatures during shipping, due to limitations on the amount of dry ice (which sublimates into carbon dioxide) that can be transported on a passenger airplane. Airlines are stepping up, however, to run chartered cargo flights, with aviation authority permission.

For all types of vaccines, although technology and equipment are prepared to maintain the cold chain, human error remains a risk. “Temperature-controlled packaging is good at eliminating temperature excursions, and our shippers are nearly error proof to condition and assemble,” says Tetz. “The most important practice is to design the cold chain—from packaging through the shipping lane—to keep the ambient temperature correct. This [design] includes standard operating procedures to ensure people take seriously how they handle the payload during shipment. Human error may cause a shipment to sit on an airport tarmac for too long, to spend too much time in a warehouse without temperature control, [or] to be opened and not properly closed at customs.”

“A vaccine shipment using dry ice needs to be completed within two days, putting added pressure on the supply chain,” adds Scott Hurley, vice-president of product marketing at Roambee. “Getting still-effective COVID-19 vaccine shipments into hard-to-reach parts of the world, such as small towns outside of large cities in less-developed countries, will be a real challenge. Without real-time monitoring, it will be all but impossible.”

Real-time monitoring using GPS-enabled and cloud-connected or cellular-connected sensors is available, and while uptake of the technology throughout the pharmaceutical industry had been limited, primarily due to cost, the urgent need for real-time data for managing vaccine distribution is accelerating adoption.

Sensor technology

Data loggers, which are passive sensors placed on packages, are widely used today by the pharmaceutical industry to indicate whether a container has experienced a temperature excursion. In addition, tracking technologies such as barcode scanning and radio frequency identification (RFID) tags can be used to track location at the time the tag is scanned. Active sensors with GPS connection, however, go one step further to provide real-time location and temperature data that can be analyzed to predict when a deviation might occur so that action can be taken to prevent product loss. These Internet of Things (IoT) sensors have in the past been costly and, so far, have been used more for personalized therapies and for track-and-trace capabilities. The challenges of COVID-19 vaccine distribution, however, are driving accelerated use of real-time monitoring, to prevent loss of any doses.

“With COVID-19 and the supply chain complexities it introduces (including multiple hand-offs and transporters), many pharmaceutical companies are understanding that it is more important to track and monitor at the package-level in real-time as they can’t assume the carrier temperature actually translates to the package temperature,” says Hurley. “Embedded IoT sensor devices with the necessary global telecom availability can capture and communicate location and condition of shipments at a granular level along every segment of an end-to-end journey, without the need for human intervention … to validate chain of custody, chain of condition, and chain of identity; all are critical to successful COVID-19 vaccine distribution.”

He notes that the cost of IoT sensors, which has been a barrier to wider use, is coming down, and that new communication technologies are reducing the power-consumption needs for IoT-sensor devices, which allows the devices to have a longer shelf life of over a year. Unlike data loggers that are typically designed for one-time use, Roambee’s sensor devices are designed for multiple uses, explains Hurley. The company has a fully managed service to handle the logistics of returning the sensor devices for charging and re-use.

SkyCell’s temperature-controlled air freight containers have embedded IoT communication systems using sensors that connect to SkyCell’s cloud-based software. “Wireless GPS tracking offers the best way to track the temperature and condition of vaccines in transit. The near real-time data means that problems can be mitigated en route rather than dealt with upon arrival,” says Nico Ros, CTO and cofounder at SkyCell. He notes that wireless tracking devices are restricted on flights, and so devices must be approved for specific aircraft.

CSafe Global has been implementing track-and-trace technology on its air cargo temperature-controlled containers for the past two years, and in July 2020 added a custom digital visibility platform from Cloudleaf to support digital tracking at the container level for parcel and cell and gene therapy handling (5). The system tracks data including location, temperature, humidity, pressure, shock, tilt, and door-open events. In September 2020, CSafe Global reported that it had completed pilot shipments that validated that the real-time sensor readings and alerts matched the validated data logged at the container (6), and the system was officially launched in December 2020 for its air cargo containers.

“The system is hardware-agnostic—any IoT sensor can be used,” says Mahesh Veerina, CEO of Cloudleaf. “Contextual data, including shipment details and customer business signals, are incorporated into the platform. The entire path is monitored automatically and tightly controlled; warnings are sent if anything begins to go outside of what is expected so that someone can intervene.”

Veerina says that Cloudleaf’s visibility platform goes from shipping through to the vaccine administration point, which involves storage, thawing, administration, and disposal. Current technology tracks individual vials using QR codes that are manually scanned, and an emerging technology being tested uses inexpensive IoT sensors on vials to further automate this step. 

He says that the industry is moving quickly to implement the infrastructure for real-time visibility. “Before the pandemic, companies were using passive data loggers and manual processes primarily to achieve FDA compliance. Now, continuous monitoring of what is happening at the container level is crucial, because losses can’t be afforded,” says Veerina.

Validating shipping protocols

Companies typically use laboratory tests that simulate shipping conditions along with real-world pilot tests, with data collected by data loggers, to validate shipping protocols. In addition, simulation software uses artificial intelligence techniques to look for potential problems and optimize routes.

“Data loggers can be used reactively to understand if specific [shipping] lanes require additional insulation, different packaging, or a different courier partner,” says Adam Tetz, director of worldwide marketing at Pelican BioThermal. He explains that when Pelican BioThermal sets up a new customer, virtual tests are run using modeling of shipping lanes, and then real-world pilot tests are run to confirm assumptions made in the model. “This information is important to have before beginning a program that may ship thousands of valuable pharmaceutical parcels each month over the course of years,” says Tetz.

Modality Solutions’ transport simulation platform simultaneously tests the worst-case scenarios for the five key distribution hazards: temperature, vibration, shock events, pressure, and humidity, says Gary Hutchinson, president at Modality. He says that pilot shipping studies are unlikely to reach one worst-case scenario at any time during a shipment and have nearly no chance of experiencing all five worst-case risks simultaneously, and he suggests that testing vaccine quality and viability under worst-case scenarios using simulation is key. Hutchinson notes, however, that actual pilot shipping tests can be used to confirm or verify that the packaging and the multiple operators needed to deliver the vaccine have been appropriately trained, and that all the necessary monitoring and controls are in place for delivery.

References

1. Pfizer, “COVID-19 Vaccine US Distribution Fact Sheet,” Fact Sheet Nov. 20, 2020.
2. Pfizer, “Pfizer Update on Our US COVID-19 Vaccine Candidate Distribution Preparedness,” Press Release, Nov. 16, 2020.
3. Moderna, “Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures,” Press Release, Nov. 16, 2020.
4. AstraZeneca, “Innovating Production and Manufacture to Meet the Challenge of COVID-19,” www.astrazeneca.com, accessed Nov. 23, 2020.
5. CSafe Global, “CSafe Global Selects Cloudleaf as Strategic Partner to Deliver a New Digital Visibility Platform,” Press Release, July 23, 2020.
6. CSafe Global, “CSafe Global Publishes Results of Second Pilot Test for New Shipment Visibility Capability,” Press Release, Sep. 24, 2020.

About the Author

Jennifer Markarian is manufacturing editor for BioPharm International.

Article Details

BioPharm International
Volume 34, No. 1
December 2021
Pages: 38–40

Citation

When referring to this article, please cite it as J. Markarian, “Accelerating Technology Adoption to Track the Cold Chain," BioPharm International, 34 (1) 2021.