The Pharma Cold Chain: More Visible, More Sustainable—and Colder

Addressing the needs of the life sciences industry for reliable, cost-effective cold chain solutions remains fertile ground for developing new technologies. Even after a decade or so of advances in insulation, refrigeration techniques, and packaging innovation, new challenges are arising: chief among these are better visibility (via data generation and transmission) of real-time actions in the transportation process; the need for comprehensive capability of ultra-low temperatures for cell and gene therapies (CGTs) and vaccines; and an emphasis on sustainable environmental practices in transportation and materials management.

Market data quantifies the growing emphasis on pharma cold chain practices. The 2024 IQVIA Global Use of Medicines report projects a 2.3% compound annual growth rate (CAGR) for 2024-28. By contrast, biopharma market growth is estimated at 15.2% CAGR by Emergen Research; multiple other market surveys are in the double-digit range. (Nearly all biopharma products are cold chain ones.) A Visiongain report from January measured the global pharma logistics market (all pharma, not just cold chain) at $93.3 billion in 2024 and forecasts a 7.5% growth rate through 2034. A ResearchandMarkets.com report from 2023 projects a 5.26% CAGR for global pharma cold-chain logistics specifically and predicts a $27.7-billion market by 2028. Looking at the CGT market exclusively, a December report from InsightAce Analytics says the current “supply chain/logistics” CGT market (which would include patient identification through to biobanking and hospital administration) was worth $1.23 billion in 2022, rising to $3.12 billion by 2031—an 11.2% CAGR.

The year 2024 is proving to be a pivotal one for pharma’s evolution. Last year saw the end of US exclusivity for Humira, AbbVie’s blockbuster biologic that ended 2022 with a record-breaking $21 billion in annual sales (2023 sales had slumped to $14.4 billion)—more or less signaling the emergence of biosimilars in the world market. There are now 45 biosimilars approved in the US, competing against 14 originator products (most of which are monoclonal antibodies). An additional 20 originator products “have biosimilars approved or in clinical development in the US,” according to a 2023 report from IQVIA. That source also notes that “the introduction of biosimilars frequently leads to higher utilization of the molecule, as lower costs offer increased access to patients.”

Biosimilar distribution is expected to slide smoothly into existing cold chain practices, notes Alex Guite, SVP and GM at World Courier, the Cencora division that handles clinical trial logistics and related services. “We’ve been working all along the way to approval of biosimilars, in Europe and the US; for us, commercialization will be ‘business as usual.’”

A somewhat mixed message arises from the CGT segment. The CGT sector experienced some cutbacks, with companies laying off employees and new ventures finding it harder to get financing (a booming stock market in early 2024 is already changing that picture). Still, the Alliance for Regenerative Medicine (which covers tissue engineering as well as CGT) counted 1,894 clinical trials going on globally (down from 2,022 trials in 2022) and the list of CGTs going from research projects to commercialization continues to grow. The vast majority of CGT work involves not only the cold chain, but the lowest, cryogenic temperatures that necessitate liquid nitrogen storage and some shipping.

“We weren’t happy with flat revenue in 2023, but you have to recognize that this is still a nascent industry, and it will not have straight-line growth from year to year,” says Jerrell Shelton, CEO of Cryoport, which provides comprehensive services to the sector. “We’re in the early stages of how the practice of medicine is changing,” he adds, noting the recent approvals of therapies for Duchenne muscular dystrophy and sickle-cell disease.

Meanwhile, events are hardly standing still in the rest of pharma. The takeup of the relatively new GLP-1 drugs (which require 2-8°C handling) reached a crescendo during 2023 as their utility as a weight-loss drug became known. At the beginning of this year, Eli Lilly announced the “Lilly Direct” program to self-distribute Zepbound, its weight-loss GLP-1 version. Earlier GLP-1 versions, including that of Novo Nordisk, were intended for diabetes patients, which itself is a huge market. Research is going on to expand GLP-1 drugs for cardiovascular and even anti-addiction therapies. Just about any form of this drug requires cold-chain delivery; Lilly packages its drug in an injectable pen that needs to be kept refrigerated. There are other direct-to-patient drug-delivery practices (usually by specialty pharmacies using mail-order), but the sky-is-the-limit aspect of these drugs will expand the cold chain market.

Cold boxes

Mostly as a result of the new vaccines that addressed the COVID-19 pandemic, but also because of the growth of the CGT sector, there are a growing number of options for “frozen” (0 to -20°C), “deep frozen” (-20 to -80°C ) and cryogenic (below -80°C ) containers for transporting biological substances. In 2023, Tower Cold Chain announced the Evolution 1600 Universal Shipper Pallet, for air or ground movement (see below). The “universal” moniker refers to its range of cooling options, from ambient to deep frozen, based on the choices of phase-change materials (PCMs) or dry ice.

Tower Cold Chain’s Evolution 1600 Universal Shipper Pallet

Source: Tower Cold Chain

Similarly, CSafe, a longtime supplier of active (powered) and passive shipping containers, announced new -20°C capability for its active RKN pallet shipper. The company also offers parcel-size passive containers for the same temperature range.

Meanwhile, Cryoport, which specializes in deep-frozen and cryogenic processes, is about to announce its Cryosphere, a cryogenic shipping device that gets around the age-old problem of conventional dewars that can tip over, affecting their cooling performance. The company says this shipper’s design allows for any orientation without affecting performance.

Another new packaging solution that was recently launched is Cryoport’s Elite -80°C Ultra Cold Shipper. It is targeted to support those gene therapies that are not able to be stored and shipped in a cryogenic environment. The Elite -80°C is available in two sizes, far exceeds standard industry hold times, and meets ISO standard 21973 for advanced therapies.

Having appropriate containers is one part of a successful shipment; the other is to have a network of services and providers that keep the shipment in compliance. World Courier announced recently three more “transport stations” (facilities to coordinate shipments) in Denver, Indianapolis, and San Diego, bringing the total to 17 in the US alone. Some of these stations are equipped with liquid nitrogen tanks and charging capabilities. “As more complex and sensitive pharmaceutical products enter clinical development, the demand for highly specialized logistics continues to increase,” comments Matt Virgilio, a regional VP for World Courier.

End-to-end visibility

The World Courier transport-station announcement aligns closely with another unveiling the company made at the same time: a real-time location management (RTLM) solution, powered by technology from Controlant, a software developer. This will be paired with World Courier’s existing transport and inventory management systems spanning the company’s global network. “Visibility” is a catchword often mentioned in supply chain circles—there are lots of claims, but the reality is that supply chains often involve handoffs to multiple providers, and getting comprehensive data coverage is difficult. “The difference with RTLM is that we are offering it throughout our network as a standard service,” says World Courier's Guite.

World Courier is by no means alone in this effort. Not only are the major international logistics companies—DHL, Kuehne+Nagel, UPS, and others—in the game, but also many of the packaging companies and the electronic condition-monitoring providers as well. There are also collaborations, like World Courier/Controlant, coming together: Elpro, a leading provider of condition monitoring in labs as well as in transit, has partnered with Tower Cold Chain for real-time tracking and condition-monitoring communication. Envirotainer, a leading provider of air-freight cold-chain containers, has integrated what it calls “live monitoring” into its Releye pallet containers, and can further link that to a control-tower service that provides ongoing review of operating conditions.

The latest entry into this visibility scramble is AeroSafe Global, which provides reusable parcels and larger containers to pharma. The company has just announced the Cold Chain Intel Service (CCIS), which builds on its existing control tower services with enhanced, artificial intelligence (AI)-based predictive control. According to Jay McHarg, CEO, “With CCIS, a customer can easily access shipment location at any time, along with the probability of a delivery interruption and thermal battery status of shipment.” He adds that this kind of detailed, real-time information is critical for the safe and effective delivery of therapeutics, particularly as weather conditions become more extreme across the globe.

Although AeroSafe Global calls this service a “core differentiator” in the market, many other organizations are pairing supply chain software with AI/machine learning (ML) techniques, and claiming better predictive capabilities as a result. Last November, for example, Cryoport acquired Tec4Med GmbH, a German software developer that “provides next-generation pharmaceutical supply chain visibility by integrating condition monitoring, cloud, and AI solutions.” Cryoport’s Shelton says that the acquisition will complement AI/ML techniques the company is already using for its CGT clients.

Meanwhile, global logistics giant DHL is pushing forward with a variety of advanced software projects, including for digital twinning (see below), the process of building software representations of the physical actions of its vehicles, warehouses, and delivery processes. With a digital twin, it’s possible to simulate upcoming shipments and analyze risk.

DHL’s digital twinning project

Source: DHL

“End-to-end visibility of cold chain shipments has never been more attainable than it is right now,” says Adam Tetz, a former marketing director at Peli BioThermal, a packaging provider, and now an industry consultant at Bright Sun Marketing. “The physical design for shipping containers now often includes accommodation for a range of form factors for internet of things (IoT) devices to track the shipment as shippers travel around the world via GPS, GMS, Bluetooth, RFID, dynamic QR code, etc. Since the underlying technologies are mature and the combined solutions of hardware and software are customized for cold chain pharma logistics, the use of these solutions will accelerate quickly this year.”

Cutting the carbon footprint

“A couple years ago, sustainability measures were a ‘nice-to-have’ part of client conversations; now they are table stakes,” says World Courier’s Guite. Historically, in a pharma cold-chain context, sustainability usually translated into offering reusable packaging, thus avoiding landfill costs, and doing what one could for reducing transportation emissions (such as shifting from air to ocean freight for international deliveries). For the most part, air freight, pallet-size containers are inherently reusable, and are typically leased rather than sold—but even there, an emphasis has been placed on lighter container weights and better volume utilization. Over time, packaging providers have made a compelling case that higher-performance (and more expensive) reusable containers could, with the right reverse logistics processes, result in lower overall costs.

“The global service networks for reusable and rental products have some major gaps in ability to service these thermal shippers worldwide,” notes Bright Sun Marketing’s Tetz. “From company to company, there are strong regional disparities; even country by country and airport by airport.” He expects these gaps to be filled with “universally robust” networks to meet pharma demands.

AeroSafe’s McHarg is bullish on his company’s capabilities for reusable containers—something the company has been touting for several years as a “cold-chain-as-a service” approach. “Once the total cost of owners is evaluated, it is easy to see the value and cost savings with a well-managed reuse program,” he says. "The key to the success of the AeroSafe Global Reuse Program (see below) is our ability to achieve a return rate of over 98%, the highest in the industry. As emphasis on environmental sustainability continues to increase, with many companies setting ambitious sustainability goals, reusable solutions will not only be environmentally responsible but also a strategic choice to enhance patient experiences and improve outcomes.”

AeroSafe’s Global Reuse Program

Source: AeroSafe Global

Some insight into industry’s current outlook on sustainability initiatives comes from a survey conducted in the fall by Worldwide Business Research, sponsors of the annual LogiPharma meetings. About 150 industry executives (mostly in Europe) were polled by the company; 85% of them said that their current supply chain practices are “somewhat sustainable.” A slight majority (55%) said that their organizations have “partially concrete goals including few defined measurable metrics.” And—watchword to service providers—51% of respondents "expect our [supply chain] partner to set auditable targets and measure progress against them” in the future.

Finally, when asked “When do you expect thermal packaging decisions to be impacted by sustainability targets?” 65% said the next 3-4 years, while 33% said the next 1-2 years. While this survey was mostly focused on packaging materials and design technology (a corporate sponsor of the survey was SkyCell AG, a provider of reusable freight containers), the overall direction seems to be clear: sustainability is a rising priority.

A mostly-US survey, just published by the Healthcare Distribution Alliance, finds similar conclusions. Of four measured criteria (on a 1-to-10 scale) of “current challenges,” dealing with sustainability was the lowest-ranked:

• Shipping lane exception management, 7.5
• Workforce skills, 6.4
• Data/technology consistency, 5.5
• Level of sustainability, 4.5

The study, “The Future of US Pharmaceutical Cold Chain Distribution,” noting the increased pace of cold-chain pharma introductions, recommends that the industry makes infrastructure investment in storage, packaging technology, and enhanced analytics to prepare for the coming surge.

— Nicholas Basta is Editor Emeritus and Founder of Pharmaceutical Commerce.