Protecting High-value Biologics at Every Turn

Ongoing innovation in the biopharma pipeline continues to bring hope to patients and prescribers everywhere. Biologic molecules, however, are inherently fragile and thus are susceptible to deterioration in the face of excursions from the refrigerated, frozen, and ultra-frozen temperatures that are required throughout every step in the storage and transit process.

The universe of high-value biologics—which includes injectable specialty medications, cell and gene therapies (CGT), and other regenerative medicines and more—has come a long way over the past decade. Further complicating the picture, a growing number of innovative CGTs and other regenerative therapies call for the highly specialized collection and transport of not just extracted blood but extracted bone marrow, spinal fluid, and other tissue types, which are then used to produce engineered therapies that are used to repair, replace, or regenerate organs, cells, and metabolic processes in the body.

The cold chain infrastructure that is needed to safeguard these products as they move from manufacturer to patients for infusion in a clinical setting or self-injection at home has also continued to evolve in terms of improved shipping container designs and insulation materials and state-of-the-art tracking and monitoring devices. At the same time, stakeholders are growing more comfortable using advanced data analytics capabilities (including artificial intelligence [AI] and machine learning [ML] techniques) and are pursuing strategic partnerships and geographically advantageous acquisitions to safeguard these critical time- and temperature-sensitive healthcare interventions.

This ongoing expansion of both experience and expertise comes at a good time, as the pipeline for CGTs and other personalized biologics continues to grow. For example, according to the Alliance for Regenerative Medicine, a dozen CGT products and gene-editing therapies are on track to be approved in 2023 in the United States and Europe (1).

“With CGT and other personalized therapies, it is critical to arrange a tightly coordinated timeline with highly choreographed handoffs among all parties involved. If you don’t have good visibility and tight control at every step of the way, there can be big clinical and financial implications,” says Samantha Betancourt, SVP marketing and strategy for UPS Healthcare. “At the end of the day, you don’t necessarily see how many hands handled the package throughout the process, but the work that goes on behind the scenes is immense and essential.”

“When you go direct to the patient—as is the case with CGT shipments and other personalized medicines—it reduces the layers in the supply chain and gets us even closer to the ultimate patient, who is usually literally sitting in a hospital room or clinic waiting for the critical infusion and hopeful that the product delivery (out part) goes off without any issues,” notes Rob Coyle, SVP, Healthcare Strategy, Kuehne+Nagel (K+N), whose cold chain delivery infrastructure includes more than 240 certified locations in more than 60 countries.

“The ultimate challenge for our customers is, of course, to ensure that their valuable, life-saving products arrive at their end point and ultimately reach the patient on time and intact,” adds Emanuel Schäpper, team lead, key accounts for ELPRO, a global provider of environmental monitoring solutions, cold chain data intelligence, and GxP services.“Stakeholders go to great lengths when it comes to selecting the most appropriate containers and packaging, choosing the right transport route, partnering with the right service provider, and implementing the right monitoring solution.”

From an operational point of view, monitoring solutions that are designed for smaller, highly individualized CGT shipments must be easy to use, reliable, and above all, they must clearly display the important information in a user-friendly format. For example, certain containers of CGT material must not be tilted or exposed to unnecessary light, so additional data loggers will be needed for those instances. “Mounting brackets and matching external probes are available for this purpose,” says Schäpper. “This allows the responsible persons to view and analyze the measurement and event data via a cloud application.”

For some biologics deliveries “the stakeholders only need to know when the parcel gets picked up, when it is in transit, when it is at the manufacturing facility and when it is on the way back to the clinic,” says Betancourt. However, in other instances, “the stakeholders want or need to know exactly where the parcel is at every moment and keep a close eye on all of the critical parameters that could imperil the critical cargo inside the package,” she continues.

Toward that end, the UPS Premier product, developed specifically to serve the pharmaceutical, medical device, and laboratory industries, is structured in three different tiers that lets customers choose the level of technology and service that is required while balancing cost considerations. The three Premier levels are:

• Premier Silver incorporates an radio frequency identification
  (RFID) sensor into the package label to provide point-in-time tracking of package location and timing throughout the journey.
• Premier Gold affixes a mesh Internet of Things (IoT) sensor (the size of a credit card) to the package to provide 24/7 monitoring and visibility regarding location and timing. Additional protection comes through access to live agents at the company’s healthcare-dedicated command center who can intervene quickly in the face of bottlenecks and disruptions.
• Premier Platinum leverages cellular and GPS tracking technology to provide precise location detail throughout a shipment’s journey and includes sensors to measure temperature, light, and humidity of the payload in the package.

Standardized versus proprietary digital platforms

Improved end-to-end supply chain digitalization is essential for improving the overall orchestration of the complex supply chain ecosystem that is required to support closed-loop, vein-to-vein CGT products and processes. Multiple courier pickups—each requiring continuous chain-of-custody and chain-of-identify verification throughout every handoff—are needed to collect the patient’s extracted blood or tissue from hospital or apheresis center, deliver the collected cells to the specialty manufacturing facility, pick up the engineered therapy, and deliver it back to the treatment center in time for the scheduled infusion back into the patient.

“Managing this complex cell journey requires that all activities are completed appropriately and according to the agreed-upon schedule with no temperature deviation,” says John Bermudez, vice president, product marketing for TraceLink, which operates the TraceLink Opus Platform that creates secure, interoperable digital networks for all industry participants using a common data model. The company is in the process of building a “cell journey solution” that will allow all parties involved in complex, multi-step CGT storage and distribution processes to work within the company’s
unified digital platform.

“There are already many world-class companies out there supplying state-of-the-art technologies for temperature-controlled packaging, sensors, data-analytics capabilities and a lot of experienced cold chain couriers,” says Bermudez. “However, the process of tying all of these parties together on a unified digital platform so that every step can be tightly synchronized remains a continual challenge.”

Today, many pharma companies working to commercialize a CGT or biologic therapy often develop their own proprietary network to coordinate the required cold chain infrastructure. “But as the number of approved therapies continues to grow—with approved CGTs and other precision biologic therapies eventually numbering in the dozens or even hundreds—having so many parallel platforms will make it difficult for healthcare providers to understand how to use them to achieve the overall objective of ensuring seamless efficiency and greater visibility,” says Bermudez.

TraceLink’s existing end-to-end digital network currently has 290,000 active members (including pharma companies, hospital and healthcare settings, providers of third-party logistics, cold-chain couriers, and more) that are able to interoperate seamlessly. “We are working to leverage that existing platform by launching our cell journey service to support CGT stakeholders,” says Bermudez. “With an anticipated launch some time in 2024, our goal is to give all CGT participants a single link to connect with each other and manage planning and real-time responses.”

Looking for insights with algorithms and analytics

In the past, cold chain monitoring solutions were limited to measuring and documenting environmental conditions during transport. “Only gradually did users realize the potential that lies dormant in the collected data, especially when the measurement data [are] combined with shipment information related to product characteristics, packaging solutions, route, service provider, and more,” says Schäpper. “Today, sophisticated data-analysis tools are used to check which routes are risky at which time of year, which packaging performs best for the respective requirements, or which mode of transport is the safest and enable continuous improvement in cold chain management.”

But retrospective data analysis is only one side of the coin. “Software-based know-how or artificial intelligence can be used to simulate the impact of changing environmental conditions (such as rising temperatures) on a shipment,” Schäpper says. Other variable developments related to a delivery can also be anticipated and built into the simulation (e.g., deviation from a route). “The simulation can then be used to calculate how much stability the product will have left when it arrives at its destination, and conclusions can be drawn as to whether measures need to be taken to secure the delivery,” he adds.

Such predictive analytics can be used, for example, to assess risk based on a simulation carried out before a delivery. Then, the combination of actual temperature data measured in real time during a delivery, in conjunction with predictive analytics, further mitigates risk. “With this method, real measured developments during the delivery can be extrapolated, and thus a risk assessment can be made,” says Schäpper.

“AI and ML have the potential to greatly enhance the healthcare logistics industry, especially in cold chain management,” adds Coyle. Specifically, he notes that such modeling modalities are already being used for:

• Real-time monitoring and tracking to help monitor and track cold chain products’ temperature and humidity levels in real time
• Predictive maintenance to predict equipment failures and maintenance needs, helping logistics companies to reduce downtime and disruptions
• Route optimization to optimize delivery routes for by analyzing historical data in order to reduce transportation costs and improve delivery times and reliability
• Demand forecasting to predict demand and adapt production and supply accordingly, manage inventory levels, and prevent overstocking or understockingmof products
• Risk management to identify potential risks, such as delays related to weather or political upheaval, equipment failures, and provide recommendations for mitigating these risks to minimize the risk of product spoilage.

Sustainability: A high priority in cold chain logistics

Sustainability is another increasingly important consideration within the biologics cold chain. Active refrigerated packaging is, by design, a more sustainable option than disposable packaging because these shipping containers can be used repeatedly. “But this approach also requires a high degree of coordination among all participants,” says Betancourt. “We can all use reusable temperature-controlled packaging, but if we are not able to get the reusable containers back through efficient logistics planning, then it doesn’t make sense.”

In May 2023, CSafe, a provider of active and passive temperature-controlled shipping solutions for the biopharmaceutical industry, announced that is providing a cold chain solution to support Krystal Biotech’s Vyjuvek gene therapy. Equipped with the company’s best-in-class vacuum insulated panel (VIP) technology, the custom thermal shipper design maintains -20 °C throughout the product journey, according to Csafe. Importantly, the supply chain for Vyjukek will be further optimized by using Csafe’s fully managed, end-to-end Retest & Reuse program. Through this program, Csafe team members inspect, clean, and thermally requalify the insulation used in these specialized shippers to ensure thermal integrity prior to reuse. This reduces unnecessary landfill waste, according to the company (2).

No company is an island

“Despite the rise in highly engineered solutions, something can always go wrong in the biologics cold chain, so the big question is what actions or interventions will need to be launched,” says Schäpper. “Against this backdrop, it’s more important than ever for pharma companies to choose partners and service providers that have the experience and expertise to provide not only technology solutions but a full range of services to intervene in the face of any event that could threaten the integrity of the biologic shipment.”

“To keep the sleepless nights to a minimum, life sciences companies must engage with their third-party logistics partners as early as possible in the commercialization process,” says Coyle. “Understanding the specific needs of the biologic products and specific details about the locations of the intended deliveries is critical to planning for the right equipment and planning to reduce the risk of delay or disruption.”

Meanwhile, service providers are always working to line up strategic partners and acquisitions that can strengthen their overall capabilities. For example, over the past year or so, SpotSee, a manufacturer of environmental condition-monitoring solutions, has acquired both Marathon Products, a provider of temperature data loggers and monitors for ultra-low and high-temperature applications, and a portfolio of patented temperature-indicator technologies that can be integrated into packaging solutions, data loggers, and monitors for the life sciences sector from Sensor International (3).

In May 2023, CSafe, a provider of thermal shipping solutions for the biopharmaceutical cold chain, and Modality Solutions, a cold chain engineering partner that has supported more than 80 drug approvals over the past three years, announced a strategic partnership to provide a next-generation cold chain solution for CGTs (4).

In August 2022, UPS Healthcare acquired multi-national healthcare logistics provider Bomi Group, strengthening the company’s global footprint by adding temperature-controlled facilities in 14 countries, and expands its scale and expertise across Europe and Latin America. “We’re constantly looking at opportunities for partnerships and are always building regional relationships, to strengthen our localized infrastructures, because different customers all over the world have so many different
needs,” says Betancourt.

References

1. Alliance for Regenerative Medicine. Sector Snapshot, April 2023: A New Vision. http://alliancerm.org/wp-content/uploads/2023/04/WEB_ARM_Sector-Snapshot_Report_R02_Web.pdf
2. CSafe. CSafe Providing Sustainable Thermal Protection for Vyjuvek Gene Therapy from Krystal Biotech. Press Release. May 22, 2023.
3. SpotSee. SpotSee Acquires Marathon Products. Press Release. May 8, 2023.
4. CSafe. Modality Solutions and CSafe Announce Strategic Partnership to Provide Integrated, End-to-end Cold Chain Solution for Cell and Gene Therapies. Press Release. May 16, 2023.

About the author

Suzanne Shelley is a contributing editor to BioPharm International.