Ensuring the Integrity of Temperature-Sensitive Drugs Along the Cold Chain: What You Can Do To Mitigate Risk

Dramatic changes in the pharmaceutical industry are forcing manufacturers to find better solutions to ensure the integrity of temperature-sensitive products along the cold chain. From shipments of active ingredients to clinical trial materials and finished products, even a minor temperature excursion during transit can have dire consequences for drug sponsors, patients and other stakeholders.

An excursion outside the acceptable temperature range can compromise product efficacy and patient safety, lead to product loss or costly quarantine for analysis, and damage company reputation. 

For more than a decade, the global pharmaceutical industry has been aggressively upgrading its shipping practices and tertiary packaging (shipping containers) for safer transit of temperature-controlled pharmaceuticals and biologics. The urgent need for temperature-assured material distribution stems primarily from several industry trends: changing product pipelines, more-stringent regulatory requirements and oversight to mitigate risk, and escalating cost and time pressure to speed medicines to patients.

Clearly, the industry needs better solutions to protect temperature-controlled-product efficacy across supply chains. Realizing the traditional cold chain and tertiary packaging are inadequate to meet current industry demands, many companies are partnering with specialized container suppliers and shippers who have the expertise, technology, and resources to ensure safe product delivery.

Trends Impacting Packaging

The dramatic growth of high-cost biologics and specialty drugs is fueling the demand for temperature sensitive packaging. Biologics are more structurally complex and temperature-sensitive than small molecule pharmaceuticals, and must be handled under specific temperature-sensitive conditions. From 2007 to 2013, the global biopharmaceutical market grew at a compound annual growth rate (CAGR) of approximately 14% and its current market value has reached $197 billion, approximately 20% of the total global pharmaceutical market. The market is expected to reach $344 billion by 2018, possibly accounting for approximately 27% of the market.1

Since temperature control can impact drug stability, biopharmaceutical companies must prove to the Food and Drug Administration (FDA), their product is maintained at its required temperature: frozen at -65°C, refrigerated at 2°-8°C, or controlled room temperature at 15°-25°C. If the temperature is not maintained, the drug product must go back to the manufacturer to check its stability data and determine if the product is within the acceptable temperature range.

Another strong trend impacting drug product shipping is more-stringent regulatory requirements and oversight, as products are increasingly being shipped to global destinations. As a result, comprehensive temperature control has replaced the traditional cold chain perspective. In 2013, the European Union codified its Good Distribution Practices (GDPs), which are rapidly becoming the required guidance worldwide. The GDPs expanded oversight to medicines such as controlled-room temperature products. Global authorities now require proof that products remain within an approved temperature range during transportation. Unlike a decade ago, regulatory authorities as well as container manufacturers now have temperature-monitoring devices.

In 2013, the European Union codified its Good Distribution Practices (GDPs), which are rapidly becoming the required guidance worldwide.

Advences in Temperature-Sensitive Packaging

Vendors of temperature-controlled packaging products have responded to the changing state of the industry and heightened regulatory expectations with new materials and technologies to transport pharmaceutical and biopharmaceutical products safely. Partnering with a highly qualified vendor you trust with the safety of your temperature-sensitive products and choosing the most reliable tertiary packaging for your needs are critical to the safety of your shipment. Trust is essential in forming a long-term, collaborative partnership for dependable shipping solutions.

Many companies are rethinking their strategies for shipping temperature-sensitive products, seeking packaging suppliers with considerable design and industry-specific expertise, and a high-level understanding of regulatory requirements, advanced technologies, and the capability of delivering efficient, cost-effective, risk-appropriate solutions.

Shippers of temperature-sensitive drug products have a wide selection of packaging options. The choice is a matter of balancing the risk, cost, and benefits of each option, and considering the value of the payload, the regulatory requirements, and the potential consequences and costs of a temperature excursion.

Manufacturers should look for shipping containers that are the smallest and lightest for the payload size, contain high-performance insulation, and have been prequalified to stringent standards in an International Safe Transit Authority (ISTA)-certified testing laboratory. They should be able to maintain the payload temperature throughout any ambient profile. Modular designs simplify the preparation and provide flexibility, allowing use of the same box for several shipping durations and temperature ranges.

Packaging with high-performance insulation, such as that in American Aerogel packaging, can extend the delivery window, keeping contents at the required temperature for a few days after arrival. This is especially valuable when shipping temperature-sensitive material to an overseas destination or to a hospital, since it eliminates concern about having to remove the product immediately upon arrival to put in a freezer, and gives physicians and hospitality greater scheduling flexibility.     

With high-performance insulation, less thermal regulation material is needed, making the package smaller and lighter than many other prequalified solutions. American Aerogel develops standard and customized packaging solutions for temperature-sensitive shipping, using aerogels and related materials in vacuum-insulated panels for thermal regulation.

To ensure strict temperature control, it is important to understand the options for thermal regulation material, including gel packs, dry ice, water, and advanced phase-change material that will freeze or thaw. The most commonly utilized packages for temperature-sensitive shipments are made of polystyrene or polyurethane, which are the least effective and require large amounts of thermal regulation material. Phase-change material, such as aerogel, reduces the size and weight of the package and extends the duration of temperature control. Aerogel based insulation has a unit of thermal resistance (R-value) of more than 10 times that of polystyrene.

For greater flexibility, some packaging companies offer rental and reuse programs. For many companies, renting packaging is highly beneficial as a more affordable option. After shipping temperature-sensitive material, the packaging company recovers the empty containers, refurbishes them, and can redeliver them to the manufacturer for its next shipment.

Looking Forward

Over the past decade, the pharmaceutical industry has been rigorously seeking advances in shipping practices for temperature-sensitive pharmaceuticals and biologics to keep pace with significant changes in the industry. Suppliers of temperature-controlled packaging have responded with technologically advanced materials to ensure the integrity of valuable medications during shipping and to effectively manage risk while meeting more stringent regulatory requirements and preserving drug manufacturers’ reputation. These industry trends are expected to continue, reshaping packaging options in the future for the safe delivery of medication to patients.


  1. Zhang J. The Global Biomanufacturing Outsourcing Market. BioPharm International, 29 (3). Feb. 20, 2015


Jay McHarg

Jay McHarg, CEO & President of American Aerogel, has 20 years of experience
in engineering, operations, and strategy, and has dedicated his career to designing, building, and delivering customer-focused results. Since 2008, he has focused his business and engineering experience on the cold chain industry, leading innovative product development and developing strategic partnerships for American Aerogel,
a company dedicated to providing the best products and services available to protect temperature-sensitive shipments. Jay leads a team of engineers and industry experts that are passionate about temperature control and work hard to provide the most innovative packaging solutions. Jay earned both a bachelor’s and master’s degree
in engineering from McGill University and an MBA from Babson College.