Can Thermal Mass Change the Cold Supply Chain?

THE TRAJECTORY OF MEDICINE is clearly making cold chain distribution the center of many discussions. The general guideline from the CDC is to maintain cold chain products between 2 degrees Celsius and 8 degrees Celsius, with a target of 5 degrees Celsius. The classes of medications that are within this scope are vaccines, diabetes care products, and biologics.¹

Due to constantly changing business models, various product configurations, and global and local distribution channels, there is no established standard to ensure that a product administered to a patient is not compromised. Some of the variables that must be managed include temperature, outbound departure times, shipping durations, payload volumes, environmental conditions, and handling processes. Basically, anything that can influence temperatures to go outside of the CDC-recommended cold chain guidelines must be monitored. It is important to note that all of these variables may impact the temperature of the actual product inside the packaging, known as the thermal mass signature of the product.²

In fact, the further down the supply chain, the more difficult it is to control. Accordingly, many products and devices have been developed in an attempt to mitigate the risk of accidental happenings that compromise the integrity of the product. These solutions are in the form of, but not limited to:

• Different packaging types that try to create the optimal environment stipulated by the end users and regulatory requirements.
• Different temperature trackers that will show, and continuously record, temperature exposures of bulk stores and shipments.

A recently published white paper by Modality Solutions (2014),³ and the World Health Organization (WHO)¹ summarized the effects of excessive heat or cold temperatures on medicines, which have the potential to create serious downstream health problems for patients administered these medications. Temperature variations can affect drug potency, efficacy, safety, and shelf life, which compromise the best health outcomes.

On packaging, the 2014 Modality study brought 5 common shipping systems into a controlled laboratory setting to test their ability to maintain the cold chain temperature profile. None of the systems maintained the specified required temperature in the first 24 hours, and furthermore, all 5 performed below expectations when tested to the ISTA 7D industry standard. A 2015 study⁴ by The Illuminate Group highlighted the trend to move toward prequalified packaging systems.

The study concluded that the volume payload is an important variable to consider on top of the temperature conditions and packaging systems. The authors demonstrated that a 500-ml volume payload experienced a different temperature profile than a 20-ml volume payload. The smaller volume immediately exceeded the 2 to 8 degree Celsius range, whereas the larger volume was intact for 20 hours. These studies brought to light the need to better control the journey of pharmaceuticals in the cold chain. Improved packaging systems need to also take into consideration the payload volume, also known as thermal mass.

On temperature trackers, attempts have been made to use expensive data logger devices to continuously record the surrounding air temperature of a payload. But as previously mentioned, this does not consider the physics of thermal mass. Temperature limit threshold indicators have also been introduced in order to reduce cost. However, these devices require a battery, which could be problematic in freezing conditions.

They also need to be calibrated, properly placed in the caseload, and lastly, can be lost during transfer. Due to these shortfalls, less costly chemical time-temperature indicators have been added as another means of measuring the surrounding air temperature of the product’s journey. A survey questionnaire was added with a chemical time-temperature indicator (label or card) to packages sent to patients by a mail order pharmacy, in order to poll the voice of the customers.

The results were not surprising, as most of the surveyed consumers desired such indicators in their packages upon receipt.⁵ This positively indicates the need for a visual indicator that can complement the packaging systems noted earlier (even prequalified systems). However, the label or card cannot mimic the thermal mass experience by the various payload volumes and configuration at the unit level. Therefore, it does not address both false positives and negatives.

Realizing that the thermal mass of a product unit is a more accurate measure for product integrity than conventional environment monitoring techniques, the National Institute of Standards and Technology (NIST) carried out a study, sponsored by the CDC. The goal of the analysis was to determine if the refrigerators commonly used to store vaccines could maintain the proper temperature profile at a unit level.⁶ NIST leveraged the thermal mass-equivalent methodology by using an ethylene glycol-filled 10-mL vial as the thermal mass equivalent of a vaccine vial with a probe connected to a recording alarm device and found a leveling of temperature to ensue from the data recorded.

At approximately the time NIST was doing its study, ThermaProx Inc. was patenting its thermal mass-equivalent indicator platform, which can mimic the temperature experiences of vaccines and other medicine types, by packaging their indicator in the same syringe or vial as the medicine or vial it was to accompany. This can show a “freeze,” or “overheat,” or both, in the same indicator.

Numerous benefits can be realized by implementing such technologies in order to improve the supply chain for the last mile of cold chain pharmaceutical products.

Conclusion

As pharmaceuticals bravely journey into 2020 and beyond, cold chain products will play a key role. Even a major shipping company, such as UPS, that was once considered just a shipping company of household and business goods, is realizing the importance of temperature control, while making significant investments to meet the need.⁷

More than ever:

• Manufacturers need to rethink product configuration, packaging, and temperature monitoring technology to ensure sustainable downstream supply chain integrity.
• Distributors need to take ownership from manufacturers to ensure the temperature profile of the product, and not just the surrounding air temperature that the unit level experienced. This is even more important as we transition into self-service mail order models.
• Health care professionals need to ensure the storage vessel (eg, refrigerators) will maintain product integrity and that the product has not been compromised at a unit level.

Regardless of the sophistication level of the packaging and attempts to control the surrounding temperature, there will always be a need to monitor cold chain products through the distribution chain, especially their thermal mass signature at the unit level. Only through proper monitoring, can we advance the ability to improve the delivery of cold chain products to patients around the globe.