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New and emerging biotherapeutic molecules drive the need for innovative solutions to meet cold-chain requirements.
Ensuring a cold-chain supply chain for biologics has always been challenging. With the emergence of newer biologic modalities, more stringent cold-chain requirements need to be developed as the industry finds solutions to address the unique challenges that these newer modalities present.
The standard cold chain is ready for refrigerated and even frozen products; however, the cryo requirements for certain biotherapeutics are challenging the supply chain both from a temperature maintenance perspective and a monitoring perspective, notes Angela Kerr, vice-president, product portfolio, SpotSee, a provider of proprietary indicators and condition-based monitoring devices for supply chain.
“The equipment needed to maintain the temperature and to measure the temperature is specialized and expensive. In developing countries, the cold-chain infrastructure is most certainly going to struggle,” Kerr observes.
Gary Hutchinson, president of Modality Solutions, a biopharma cold chain engineering company, notes that the most significant difference with the new COVID-19 vaccines is the challenge of identifying the effect of stressing the vaccine with a range of transportation hazards (e.g., shock, vibration, pressure, and humidity) concurrently while maintaining cryogenic temperature conditions. “Verifying the safety and quality of these new biologic modalities in a complex delivery network will require better characterization and validation with transport simulation technology,” he says.
Hutchinson explains that, once at the administration site, the vaccine thaw rate and stability at refrigerated temperatures require time-definite delivery and new controls in pre-administration procedures. Otherwise, there is no guarantee of vaccine efficacy. Tracking these time-out-of-temperature events across the complex supply chain will be a significant challenge, too, he emphasizes.
Current cryogenic shipping containers typically rely on vaporized liquid nitrogen to maintain these ultra-cold temperatures, Hutchinson explains; however, these containers are susceptible to failure if the proper orientation (i.e., vertical orientation) is not followed. “With the increased use of these cryogenic shippers, the availability and complexity at the administration site will be an ongoing challenge,” he adds.
More efficient shipping timelines is one solution. However, accelerated timelines require transport simulation technology, Hutchinson says. Accelerated timelines are needed to keep up with the pace of innovation needed for emerging new COVID-19 variants, for example.
“Since so little is known about the robustness of this new [biologic] modality, and new variants are arriving monthly, transport simulation studies designed to confirm the quality of the vaccine across a complex global transportation network are the only way to complete the required validation in the accelerated timelines,” says Hutchinson. “When Operation Warp Speed is required, the new variants will need the speed and accuracy of transport simulation to confirm the safety and efficacy of these new vaccines.”
Kerr points to specialized recorders, which are currently available for monitoring the cold chain, as another solution to maintain biologic product integrity. Development of solutions that are more economical will also certainly emerge, she adds.
In terms of other approaches to address cold-chain requirements, Kerr emphasizes that the experience with COVID-19 required biomanufacturers to do whatever it took to get to a solution. “There are certainly efforts that are being explored to meet standard cold chain or avoid cold chain completely,” she states.
Hutchinson says that Modality Solutions has worked with clients to evolve formulation approaches and test the robustness of formulation solutions at differing temperature ranges. “The formulation is dependent upon and must be tested against the practical limitations of the cold chain. A vaccine that cannot be delivered safely and effectively is of no use to anyone. After the initial testing to set temperature requirements, a review of the capabilities in the supply chain sets the testing parameters,” he says. Once scientists reviewed the risks and made formulation changes, the newer vaccines were tested using (Modality Solutions’) transport simulation technology. This allowed the scientists to confirm the viability of a vaccine from the point-of-manufacture to the dosing of the population.
Hutchinson points to the example of Pfizer, which changed its cold-chain requirements during the pandemic. “These changes relieved significant pressures on the delivery network. However, these changes were only possible with better characterization of the robustness of this new modality. The characterization process for robustness in the cold chain can be shortened from months to weeks using transport simulation technology,” says Hutchinson.
The future of supply chain operations will depend to a certain extent on the evolution of these increasingly complex biologic. The COVID-19 pandemic proved to be a real test of the biopharma cold chain, Hutchinson states. “I think we were largely successful through heroic efforts. However, the future of supply chain operations is a complete revamp of the network that focuses on robustness and risk management. Too many operational steps that were taken for granted were shut down in the pandemic. The cold chain adapted on the fly. In the future, these adaptions will be alternatives that will be tested and integrated into a more robust and diversified cold chain,” he says.
Hutchinson expects that the future of supply chain operations will start with formulation development to match cold-chain capabilities. He explains that such a future will be especially true if a mass vaccination program is needed to stave off the next pandemic. The approach will also be best-practice when the promise of these new modalities is used to address other significant diseases.
Meanwhile, packaging is also expected to play a role in allowing new modalities to meet the requirements of the cold chain in the future. “Packaging is responsible for making sure products can be moved safely through the supply chain. Packaging companies and engineers are given the transport/storage conditions that are required to maintain the efficacy of these products so they are always looking for methods that will maintain these dramatic temperature conditions,” says Kerr.
Hutchinson says that the most significant change in packaging being seen is how the issue with orientation for current most-used packaging solutions is being addressed. Alternative designs and refrigeration are in development and being qualified and verified across the industry, he notes.
“A change in process development will eliminate the need for specialized packaging in the future,” Hutchinson adds. “The most significant change is not better packaging, but a better understanding of the vaccine robustness at more standardized temperatures (e.g., 2–8 °C or ≤ -65 °C),” he says.
He also acknowledges that the industry recognizes the fact that technological innovations will take time to be adopted; however, if the stability and efficacy of the vaccine are confirmed at more-common temperatures with the current supply chain infrastructure, then cold-chain challenges in the future will be reduced.
Modality Solutions is also working to better understand the non-traditional shock and vibration events on these next-generation modalities. “These vaccines are delivered into emerging markets with less sophisticated transportation infrastructure in non-traditional transport equipment. For example, military trucks, helicopters, and, in some cases, drones are being used as the primary method of transportation,” he explains.
“These types of equipment on more primitive infrastructure have a significantly different shock and vibration profile than advanced nation infrastructure. These differences must be characterized and tested to confirm the viability of the vaccine after delivery to every corner of the world,” he states.
Feliza Mirasol is the science editor for BioPharm International.
Vol. 35, No. 1
When referring to this article, please cite it as F. Mirasol, “Finding Solutions to Cold Chain Supply,” BioPharm International 35 (1) 40–41 (2022).