The cold chain’s weakest link is no longer the box

Atemperature-controlled pharmaceutical shipment can leave a manufacturing site with a validated shipper and still face its greatest risk thousands of kilometres later. At an airport, warehouse, customs checkpoint or during final delivery, the conditions surrounding the package can matter as much as the package itself.

A case study presented by Andress Lam of Cathay Cargo during an IATA cargo and pharmaceutical session in September 2025 illustrates the point. During a temperature-controlled shipment from Los Angeles to New York, an IoT device recorded a rise from around 24°C to 30.1°C at an airport facility. The excursion occurred between 09:15 and 09:30. The data identified the location and indicated equipment failure. According to the case study, the time required for the investigation fell from days to minutes.

The package was not necessarily the weakest link. The network was.

Biologics now account for an increasing share of pharmaceutical supply lines. Industry analysis, drawing on Nature Biotechnology, indicates that biologics account for about 40% of pharmaceuticals in development at major pharmaceutical companies, with the proportion expected to exceed 50% by the end of the decade.

The temperature challenge is also becoming more demanding. CPHI’s 2026 analysis states that refrigerated biologics generally require 2–8°C, while frozen products may require –20°C or colder. Some ultra-cold therapies require –80°C or below, while certain cell and gene therapies may require cryogenic conditions below –150°C.

The commercial scale is rising at the same time. Precedence Research estimates the global biologics market at $487 billion in 2025 and projects it to reach approximately $1.24 trillion by 2035, representing a projected CAGR of 9.83%. These are market estimates and projections, not observed future values.

The implication is straightforward: as biologics become more commercially important, access to suitable cold-chain infrastructure becomes a potential constraint on market expansion.

The cold chain is not a single operation. It is a sequence of interdependent hand-offs: manufacturing, packaging, storage, airport handling, air freight, customs, regional distribution and last-mile delivery. Every transfer creates another opportunity for delay, temperature excursion or loss of visibility.

In his July analysis, Dave Malenfant, a supply-chain expert and founder of MDM Consulting, argues that companies seeking to streamline last-mile validation must first understand their transportation network in depth. This includes border and import controls, which can expose temperature-sensitive shipments to delays or inspections.

The IATA and Cathay Cargo case study demonstrates why continuous monitoring matters. The shipment temperature rose from 24°C to 30.1°C at an airport facility. IoT data identified the timing and location of the excursion and indicated equipment failure. According to the case study, the digital record also helped identify responsibility.

A validated shipper cannot compensate indefinitely for a poorly controlled hand-off. That distinction is increasingly important as pharmaceutical supply chains become more fragmented. The question is no longer simply whether a container can protect a product under validated conditions. It is whether the entire route can maintain those conditions.

This does not make packaging less important. It changes the question being demanded of it.

Reusable containers can reduce packaging waste across repeated journeys, but they require reverse logistics, cleaning, tracking and asset availability. Single-use systems may be easier to deploy in fragmented or one-way networks, but they can increase material consumption and recurring costs.

The relevant comparison is therefore not simply reusable versus single-use. It is the performance of the entire logistics loop.

Route length, infrastructure, asset recovery, temperature profile, monitoring and contingency arrangements all affect the outcome. A container which performs well under validated conditions may not be the optimal solution for a route exposed to unpredictable delays or limited infrastructure. This is where packaging strategy increasingly intersects with supply-chain design.

IoT sensors, GPS tracking, cloud platforms and continuous temperature monitoring are changing what pharmaceutical companies can see. The harder task is turning visibility into the capacity to intervene.

The IATA and Cathay Cargo presentation shows the value of continuous, time-stamped data. Temperature, location and handling events can provide a more precise record of an incident than conventional milestone tracking.

Anil Kane, global head of technical and scientific affairs for Pharma Services at Thermo Fisher Scientific, explained in 2023, reflecting on CPHI Barcelona, that there was already strong interest in applying AI to every aspect of pharmaceutical development, from discovery to clinical trials and the supply chain. The challenge, he said, was to identify the right applications and assess their value-added outcomes.

​​​​​​​In 2025, speaking at DCAT Week, Kane also emphasised the need to monitor market demand and therapeutic trends, and to use digital and data-driven tools to improve decision-making across the development and manufacturing journey.

For cold-chain logistics, however, visibility is only the first step. The strategic question is whether temperature, location and handling data can become sufficiently interoperable and actionable across organisational boundaries.

A sensor can tell a company that a shipment is getting warm. Resilience depends on what happens next.

No packaging technology can eliminate disruption caused by airspace restrictions, customs delays, airport congestion, conflict or changes in transport capacity.

That creates a familiar but increasingly important set of trade-offs: efficiency versus resilience; just-in-time logistics versus inventory buffers; centralisation versus regional redundancy.

For high-value biologics and advanced therapies, the consequences can be particularly significant. A conventional medicine delayed by several hours may remain usable. A product requiring continuous temperature control, or a personalised therapy with a narrow treatment window, can face a very different risk profile.

Cold-chain strategy is therefore becoming part of pharmaceutical supply-chain resilience. The question is no longer simply which route costs least. It is which route can maintain product integrity when the preferred airport, carrier, warehouse or border crossing becomes unavailable.

The economics of cold-chain distribution must move beyond the cost of the shipper.

The calculation increasingly includes qualified storage, specialised transport, monitoring, data infrastructure, contingency capacity, inventory buffers, compliance and product loss.

Industry estimates attributed to the IQVIA Institute for Human Data Science put losses caused by temperature-controlled logistics inefficiencies at around $35 billion annually. These figures cover lost pharmaceutical products and associated costs, such as recalls, investigations and impacts on clinical trials.

For a high-value biologic, a more expensive packaging system or redundant logistics option may appear inefficient until the alternative is a failed shipment. The more useful metric may therefore be total cost and risk per successfully delivered dose, rather than cost per shipment. That changes cold-chain procurement from a packaging decision into a supply-chain investment decision.

The strategic implication is clear. If distribution capability can determine whether a biologic reliably reaches a patient, cold-chain requirements need to be considered earlier in product development and market-access planning.

Formulation stability, allowable temperature excursions, packaging architecture, distribution hubs and target markets are increasingly interconnected decisions.

For advanced therapies, cryogenic requirements impose constraints on storage, transport, monitoring and handling as much as on the container itself. The industry has spent decades engineering better boxes. The next challenge is to engineer better networks — networks which combine qualified infrastructure, intelligent packaging, interoperable data, contingency capacity and resilient routes.

For biologics, the cold chain is no longer simply a logistics function. It is part of the product’s path to market.