Labels That Withstand Liquid Nitrogen

The requirements for today’s pharmaceutical supply chains extend far beyond refrigerated storage. Traditional medicines are often stable at room temperature or within standard cold ranges, but modern biopharmaceuticals push the limits. Vaccines, monoclonal antibodies, and Advanced Therapy Medicinal Products (ATMPs) often demand storage at –20 °C, –80 °C, or even in liquid nitrogen at –196 °C.

Such conditions create unique labeling challenges. Conventional adhesives lose strength as they reach their glass transition temperature, and even microscopic layers of ice can prevent proper adhesion. Once a label detaches or becomes unreadable, traceability is compromised—posing both regulatory and patient safety risks. “If identification fails, the integrity of clinical studies and product quality are immediately at stake,” explains Frank Jäger, Commercial Director worldwide at CCL Clinical.

Meeting Regulatory Expectations

Alongside technical durability, labeling must fulfill regulatory requirements. Since 2022, the EU Clinical Trials Regulation (No. 536/2014) has unified labeling rules for investigational products. Annex VI demands that trial materials carry clear, permanent information, including expiration dates, unless specific exemptions apply under Delegated Regulation (EU) 2022/2239. In practice, this means labels must remain legible and intact under the harshest conditions.

Testing Beyond the Certificate

“True reliability starts with material qualification under realistic conditions,” says Jäger. Certificates from suppliers are useful, but not sufficient. Adhesion can vary depending on when the label is applied (before or after freezing), the state of the surface (dry, moist, frosted), the shape and material of the container, and stresses from repeated freeze–thaw cycles.

Research confirms that at –20 °C, a thin film of moisture can reduce bond strength by up to 70%. To mitigate this, CCL Clinical uses in-house validation protocols: materials are first preselected based on supplier data and then tested internally against strict quality criteria, including performance after multiple freeze–thaw cycles. Only then is long-term suitability confirmed.

Tailored Label Designs

With the right materials qualified, the next step is thoughtful label design. Wrap-around labels have proven effective for vials and syringes, offering ample information space by overlapping multiple times. Cold-active adhesives that remain viscous instead of crystallizing are also key to ensuring adhesion, even when surfaces are not ideal.

Transfer Labels for Flexibility

In some scenarios—such as randomized trials or patient-specific ATMPs—containers are frozen before final label content is available. Here, transfer labels provide a practical solution. Applied in advance, they act as a protective layer and preserve the adhesive surface for later application of the final label, even when the container is already frozen.

Ease of handling matters too. In cryogenic environments, staff wear heavy protective gloves, which reduce dexterity. CCL Clinical has therefore designed transfer labels with large, silicone-coated pull tabs. These allow quick removal without damaging the adhesive surface. “Small design details like this make a big impact on reliability in practice,” Jäger notes.

Closing Perspective

The challenges of cryogenic labeling cannot be solved by material choice alone. Reliable performance at temperatures down to –196 °C requires the right combination of validated materials, advanced adhesive systems, practical label designs, and strict regulatory compliance.

“As specialized label suppliers, we play a central role in protecting the integrity of the pharmaceutical supply chain—and ultimately the safety of patients,” Jäger concludes.

CCL Clinical

The CCL Clinical Business Unit is the global specialist of CCL Industries Inc. for products and services in the clinical trials sector. With locations in the USA, Canada, Europe, and Asia, it brings together decades of experience and expertise from hundreds of professionals. This international presence, combined with a strong foundation in local markets, enables CCL Clinical to offer flexible capacity at the highest quality standards.

The product range includes booklet labels, package inserts, folding cartons, and innovative labeling solutions with RFID and E-paper technology – all tailored to meet the needs of the research-based pharmaceutical industry. In addition, customers benefit from a wide range of services, including modeling, phrase libraries, label design, routing, randomization, and variable data printing, which support the entire lifecycle of clinical trials.