COVID-19 vaccine development and rollout were crucial to gaining control of the pandemic. When the success of these efforts became dependent on the ability to maintain lower than typical temperatures during distribution, the importance of reliable and continuous cold chain solutions for mRNA-based formulations was thrust into the spotlight. Beyond pandemic mitigation measures and outside of COVID-19 control, vaccines and therapeutics are increasingly leveraging the power of temperature-sensitive cells, proteins, and nucleic acids in preventing and treating disease. With the pharmaceutical industry shifting toward using biological molecules as medicine, there’s a need to emphasize cold chain logistics and access to innovative, reliable cryogenic solutions.
Pharmaceutical products containing biologically active components often require adherence to special handling instructions from manufacture to administration, as strict temperature regulation can ensure safety, stability, pharmacological activity and clinical efficacy remain uncompromised. A key step in developing these compounds is outlining temperature requirements and implementing logistics to maintain those temperatures throughout production and transport. By incorporating a cold chain strategy early on, researchers can set the stage for a more seamless scale-up and an efficient transition to cGMP manufacturing and commercialization.
Below are five vital steps labs can take to create secure cold chains for temperature-sensitive materials when trying to get production off the ground.
1. Understand and define clear storage condition requirements for your sample.
A first step to building a secure, reliable cold chain is defining what conditions you need that cold chain to maintain. Determining the temperatures that will keep a product stable is key to developing this understanding. Metrics that should be assessed include the following:
- The desired target storage temperature.
- Acceptable temperature tolerance from the target temperature.
- The point at which systems should alarm if a tolerance boundary is crossed, potentially compromising sample integrity or viability.
While temperature specifications for raw materials might be provided, determining this information for a finished product at each stage within a process will often require dedicated, extensive testing.
2. Create a qualification protocol to validate the performance of each cold chain asset.
Building an effective cryogenic cold chain will likely require purchasing and implementing specialized equipment or cold chain assets. Qualifying cold storage equipment involves running a set of test conditions to ensure an asset can adequately achieve the previously outlined temperature requirements. This exercise typically involves both empty and cargo tests, with probes deliberately positioned to capture temperature variation within the cabinet to simulate a sample’s exposure to temperature changes over time within the asset.
To maximize a sample’s time spent at the desired temperature while providing the largest margin for alarm limits, a cold chain asset’s qualification protocol should include analysis of certain key metrics that statistically represent temperature characteristics and fluctuations. These measures include temperature uniformity, or the consistency of temperature measurements over time, and peak variability, or temperature fluctuations in the cabinet.
3. Account for temperature requirements in production and distribution strategies.
When moving a vaccine or therapeutic formulation from a manufacturing location to bulk storage and, ultimately, target markets, it’s vital to ensure your product remains stable and maintains intended efficacy during each part of the journey. Many cold chains leverage a “hub and spoke” distribution model, with hubs storing bulk product and spokes carrying finished formulations to and from end markets using cryogenic instruments and packaging. Keeping products cold during transport is key to any cold chain strategy. If needed, logistics partners can help overcome the many challenges accompanying this part of the process.
Cold chain storage and transport challenges became evident during the COVID-19 vaccine rollout when many labs and hospitals tasked with maintaining doses at ultra-low temperatures struggled to implement the necessary associated procedures, systems, and safeguards. Ultimately, millions of critically needed doses were wasted across the country, some due to cold chain failures. In an effort to eliminate waste and prevent temperature excursions, the CDC points to the use of appropriate temperature monitoring devices and backup storage units.
4. To create storage hubs, partner with an established manufacturer of reliable cold chain assets.
In addition to maintaining necessary temperatures, cold chain equipment should come with a warranty indicating the manufacturer’s confidence in the product’s long-term performance. Service contracts are also helpful in complying with preventive maintenance schedules, ensuring assets are functioning optimally, and possibly facilitating a quicker turnaround for unanticipated repairs. Finally, purchasing associated temperature recording and remote monitoring equipment can offer added peace of mind, allowing teams to protect valuable products and maximize asset uptime with real-time insight into performance status from anywhere.
When decentralized, regional labs are looking to ramp up development. They need cold chain assets. Collaborating with a reliable manufacturer can offer both equipment, and scientific expertise can maximize efficiency. The value of partnership was made evident during South Korea’s recent efforts to control the COVID-19 pandemic when the country worked closely with a manufacturer to quickly deploy cold storage solutions and establish a systematic workflow for vaccine development. Ultimately, through this collaboration, South Korea was successful in fast-tracking a national, home-grown vaccine development program and became a top global vaccine manufacturer.
5. Secure your cold chain for years to come with dependable equipment and proper documentation.
Standards for cold chain management are helping labs choose effective cold chain equipment. For example, in 2021, NSF International developed freezer and refrigerator standards for the American National Standards Institute (ANSI), designed to support vaccine storage and distribution efforts. Adherence to these standards is not required, but the extensive validation testing conducted through the NSF certification process can help labs confirm a product will be able to reliably perform within a cold chain as needed.
Building a robust cold chain set for long-term use also means ensuring that certain essential information is available for compliance. For example, regulators are likely to request scientifically sound data supporting the reliability of each asset within your cold chain and the effectiveness of the distribution strategy as a whole in maintaining necessary temperatures from manufacture to patient administration. These exercises will not only help expedite regulatory reviews and approvals, but they will also result in a continuous, dependable cold chain that labs and manufacturers can rely on for many years to come.
Whether serving local populations or working toward global distribution, labs are increasingly relying on cold chains to deliver temperature-sensitive treatments and vaccines. Using cryogenic instruments, real-time monitoring tools, specialized packaging and innovative logistics solutions, these critical products can be safely stored and efficiently transported at the conditions needed to ensure stability, pharmaceutical activity and efficacy are maintained along the way.
Ryan White is a senior product manager at Thermo Fisher Scientific. He is responsible for the company’s ultra-low temperature freezer product line and led this area during the height of COVID-19 vaccine research and development efforts.