Best practices for temperature controlled biologic packaging and storage

Playing it cool: Temperature control considerations for biologics

With the recent regulatory approval in the United Kingdom of Casgevy™ — the world’s first CRISPR/Cas9 gene-editing therapy to be cleared for use in patients — biologics are poised to become a major component in the future of medicine. A broad term comprising many different types of products derived from a living source, biologics include everything from cell and gene therapies (such as Casgevy) to vaccines, blood, hormones, proteins (such as insulin), monoclonal antibodies, and tissues for transplant.

Because of their biological origins, biologics have very specific needs to maintain their viability. At the top of this list is temperature control, which encompasses a number of possible categories including cryogenic (-185°C), ultra-low frozen (-80°C), frozen (-20°C), refrigerated (+2° to +8°C), and room temperature stable (+18°C to +24°C).

Temperature excursions — fluctuations to a higher or lower temperature than the biologic’s specified parameters — can have a dramatic effect on the stability of a biologic, and can negatively impact the safety or efficacy of a product by the time it gets to the patient. There are a variety of elements that contribute to the safety and stability of biologics at controlled temperatures. Here, we’ll explore considerations for temperature-controlled packaging, storage, and monitoring of biologic materials.

Primary packaging for cold temperatures

There are many packaging factors that can impact temperature stability. Some of these include the heat transfer properties of a container’s material, or the container’s strength and resistance to pressure or temperature changes. Using primary packaging materials that are designed for use at cold temperatures becomes critical to prevent temperature excursions, breakage or contamination. Glass, for instance, is liable to crack when undergoing large, quick shifts in temperature, such as in the thawing process when a frozen treatment is being prepared for use. Other materials, such as certain resins or polypropylene, are better suited for this usage.

Another concern for primary packaging is container closure integrity (CCI), or the ability of a container to maintain a sterile barrier throughout its shelf life. At extremely cold temperatures, the properties of closure materials may change, such as through shrinkage or loss of elasticity. As a result, vial stoppers may no longer fit precisely, or seals may be broken, allowing the entry of microbes or gasses that can change the pH of the therapeutic, or over pressurize the container. For this reason, it is of vital importance to select containers and closures that maintain CCI at the target temperature.

Finally, an element critical to the effective packaging of biologics is the use of labels designed for extreme temperatures. However, selecting the right approach to these types of labels can be challenging: When applied at low temperatures, for example, some label adhesives may have difficulty bonding to the surface of a biologic vial. Yet, labeling at warmer temperatures after the biologic has been placed in a vial may put the therapy at risk. Further, plastic labels tend to become rigid and shrink at cold temperatures, increasing the likelihood of these labels peeling or falling off. To solve this problem, some manufacturers have designed labels using materials specifically intended for harsh conditions, such as thermoplastics. Others, however, have engraved or printed information directly onto the vial, bypassing the need for an adhesive label.

Temperature-controlled storage

When storing biologics at low and controlled temperatures, there are a few approaches available. One option is to use freezers, which are capable of ultra-low and even cryogenic temperatures. Controlled-rate freezers are designed to carefully control how quickly a biologic cools, providing consistency and preventing damage to the product. However, these are meant primarily for preparation, meaning a different freezer platform will be needed for long-term storage. Another option is the use of dewars — large flasks that utilize liquid nitrogen and vacuum insulation to maintain temperatures for the biologic contained within. These are primarily used for cryogenic storage, and are available as smaller manual-fill dewars and larger, autofill systems.

A key factor to consider in temperature-controlled storage is the length of time that will be required. While the optimal temperature range may differ based on biologic type, in many cases, it also may change depending on how soon the product will be accessed. If storage is intended for the long term, it is likely that a much lower temperature will be required to maintain viability, while short-term storage of the same biologic may call for a higher temperature category.

Ensuring sustained integrity is central to establishing reliable long-term storage. For instance, a backup power system guarantees the maintenance of controlled temperatures in the event of a power failure. When storing biologics with a third party, a robust inventory maintenance system provides oversight of the location and condition of every product. And, last, but not least, continuous monitoring protects the stability of valuable biologics.

Temperature monitoring

Because maintaining the correct temperature is so vital for biologics, it becomes imperative to have a reliable method of surveilling the status of stored products. For monitoring of biologics in a static location, internet-enabled wireless sensors allow for continuous data tracking. Such devices can send status alerts to responsible personnel, or even sound an alarm when temperature excursions occur. By continually uploading temperature data to the cloud, these sensors allow access to temperature information at any place and time, as well as an ongoing record of temperature data. 

Additionally, automated data monitoring through wireless sensors is much more reliable than manual checks, as it offers consistency and provides the added benefit of not requiring personnel to carry out these checks. Even so, it is important to have personnel ready to react to any alerts or alarms promptly, and to have a plan in place specifying the appropriate response.

For monitoring during transit, a similar tool, known as a data logger, provides a record and alerts regarding a biologic’s temperature condition when it is en route. However, wifi access may not be consistent in all areas of travel, making continuous data upload challenging. Another option is to utilize temperature indicators, which are mounted on containers to provide a visual warning when a temperature excursion has occurred, and may be manually checked at major touchpoints in the journey. However, these can provide little additional data, and may not offer details such as the time of the excursion or how long it lasted. 

In addition to temperature, it is also advisable to monitor other factors that may impact the viability of a biologic, including humidity, air pressure, and carbon dioxide levels. Many digital monitors include these capabilities to better safeguard the viability of products under temperature control.

Pieces of a larger puzzle

Once a biologic’s stability has been ensured by proper packaging and storage, it is ready to be transported to the patients who need it, when they need it. However, the transport of temperature-controlled products introduces a new set of complex challenges, such as carefully controlled shipping containers, regulatory and customs expertise, and ensuring the visibility of the supply chain. Additionally, promoting energy efficiency and sustainability is a rising concern in temperature-controlled transport. To help navigate these challenges, it is imperative to find a partner experienced in temperature-control logistics, with the capabilities designed for protecting the integrity of biologics.

Learn about Yourway’s temperature-controlled packaging, storage, and distribution solutions.

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