Contributed Commentary from Timothy Root

December 23, 2021 | Decentralized clinical trials (DCTs) have been present in clinical research over the past decade. However, as over 28,000 active clinical trials were paused in 2020 due to the pandemic, they were thrust into the mainstream and are not going away. These types of trials, which range from at-home to hybrid clinical settings, mitigate the burden of transportation, lodging, meals, and dependent care that often pose barriers to study participants. These barriers are daunting to any clinical trial but particularly prevalent with consideration for specialized and rare disease treatments, which represents a large and growing percentage of drug development currently. By removing them, DCTs can help accelerate patient recruitment, reduce dropout rates, and even help increase the size and diversity of the patient population.

Still, the adoption of DCTs requires a fundamental shift in infrastructure to maintain compliance. This not only includes a shift to the cloud for virtual collaboration between stakeholders and data sharing, but also the elements of infrastructure that cannot be virtualized, such as the cold chain.

Implement Flexible Infrastructure

To further DCT adoption, the Decentralized Trials & Research Alliance (DTRA) has cited the need for new resources for the reliable application of ancillary products in remote and dispersed settings where biomedical and facility infrastructure is limited. This includes remotely managing ultra-low temperature (ULT) storage, as many of today’s advanced investigational medicines are increasingly temperature-sensitive. As drug developers explore new investments to enable DCTs, new technologies and solutions will be crucial to establish this flexible ultra-cold-chain (UCC) of custody.

Couriers can be equipped with portable cold containers packed with dry ice or phase change materials (PCMs) to move temperature-sensitive materials for clinical trials like we have seen in the COVID-19 vaccine deployment. Once biologics that require ULT storage are frozen and distributed, the cold chain must be maintained and tracked just like traditional trials. This can require long-term storage in remote locations that lack the space, electric power, HVAC systems, or network infrastructure needed to effectively operate conventional ULT freezers. While dry ice will continue to have a role to play in UCC, this method is not without challenges in DCT settings where there are no trained personnel on hand, such as thermal instability, handling complications, need for special training and potential hazards without proper ventilation.

Another option would be use of portable ULT storage appliances, which are available now on the market. With the flexibility to plug units into a standard vehicle power adapter and program setpoint temperature between -20°C and -86°C, these freezers mitigate the challenges that traditionally accompany dry ice. Furthermore, where traditional ULT freezers are too bulky and have special infrastructure needs, more compact units are better suited for decentralized trial locations and a broad range of advanced medicines now entering the drug pipeline.

Lastly, portable ULT flexibility and mobility could be further enhanced with the combined use or reuse of phase change materials (PCM) and battery backup systems for additional protection against temperature excursions that pose risk to sample integrity during limited time periods where power is not accessible.

Adopt Real-Time Monitoring Practices

Temperature monitoring and logging has long been a pre-requisite in the cold chain for regulatory compliance purposes. However, the emergence of cloud infrastructure, coupled with Internet of Things (IoT) devices, presents a new opportunity to monitor the chain of custody for ULT assets continuously and actively—not just in commercial drug delivery but in DCT scenarios as well. By equipping ULT freezers with cloud-based monitoring of temperatures via wireless probes and network access points, freezer cabinet temperatures can be monitored and logged from any desktop or smart device web browser. The potential to integrate this freezer data into the cloud with clinical trial management platforms enables seamless Good Manufacturing Practice (GMP) and regulatory compliance, as well as superior DCT management.

Tailor Strategy to Organizational Needs

When adopting new DCT solutions and technologies, the most important thing leaders can do is continuously evaluate the specific needs and challenges of study stakeholders. ULT freezer providers can be partners to trial sponsors, managers, and participants in responding to the growing demand for DCTs. This entails offering flexible leasing and financing terms that align with clinical trial schedules, flexible shipping options and "white glove" services that alleviate logistical challenges, and assisting in the deployment of ULT freezer fleets for these new transient and remote applications.

Through this partnership, the industry can collectively establish the more flexible ultracold infrastructure needed to support the future of hybrid and decentralized clinical trials. As we look to the future of medical innovation, particularly in the areas of rare disease and specialized cell and gene therapeutics, many of these advanced interventions will require ULT infrastructure to maintain their integrity. The new standard of flexible and connected DCT infrastructure will contribute to the success of these trials, as well as superior outcomes across patient populations for the treatments that go to market.

Timothy Root is Marketing Director, Stirling Ultracold. He can be reached at troot@stirlingultracold.com.