top of page
cropped-PRONAV_Clinical_colour.png

The Science of -80°C Storage: Why It Matters for Phase 1 Clinical Trials

  • PRONAV
  • May 13
  • 5 min read

For biotech and pharmaceutical companies developing biologic therapies, ultra-low temperature storage (aka -80°C) is not just a logistical hurdle; it’s a critical factor in ensuring drug stability, regulatory compliance, and ultimately, trial success. Biologics – including antibodies, mRNA vaccines, and cell and gene therapies – are highly sensitive to temperature fluctuations(1). If they’re not stored correctly throughout the entire clinical trial supply chain, these molecules are likely to degrade(2), leading to loss of potency, regulatory setbacks and costly trial delays. 


Despite it's importance, many companies underestimate the complexities of ultra-low temperature storage in clinical trial supply chains, potentially compromising the stability, efficacy and safety of the drug before the trial has even begun. This article discusses the importance of -80°C storage, explores the risks associated with improper handling, and outlines some best practices for maintaining drug integrity throughout Phase 1 clinical trials. 


The Science Behind -80°C Storage for Clinical Trials


Why -80°C?

It is well understood that proteins, nucleic acids, and cells – all of which are components of biologic drugs – are inherently unstable at ambient or refrigerated temperatures(2,3). This is because, at higher temperatures, proteins denature and, therefore, lose their function due to unfolding, aggregation, or degradation(4). RNA-based therapies also degrade rapidly at higher temperatures, leading to a loss of therapeutic activity(5). Viral vectors and cells used in cell and gene therapies also become non-viable following exposure to higher temperatures, thereby impacting their efficacy(6). 

However, ultra-low temperature storage significantly slows down molecular degradation by reducing biochemical reactions such as enzymatic degradation and protein aggregation, preserving biologic drug stability and efficacy as a result. 


Person loading a -80°C freezer


The Impact of Temperature Excursions

Even a single, brief temperature excursion beyond acceptable limits can impact the efficacy of a drug and the safety of trial participants, rendering an entire batch unusable(7). Therefore, temperature fluctuations have significant cost implications for sponsors and, moreover, risk regulatory noncompliance, which can delay or even stop trials completely. Consequently, maintaining a fully validated -80°C cold chain from storage to clinical sites is a non-negotiable for trial success. 


The Risks of Improper Cold Storage in Clinical Trials


Failing to maintain -80°C storage conditions can result in serious scientific, regulatory, and financial consequences(3,7):


  • Loss of Drug Potency – If a biologic drug degrades due to improper storage, it may no longer work as intended, invalidating trial results and compromising patient safety. 

  • Regulatory Compliance Issues – Regulatory bodies often require validated cold chain documentation, including temperature monitoring logs, deviation reports (in the case of temperature excursions), and proof of stability data under the actual storage conditions. Failure to maintain or document precise temperature control can lead to regulatory penalties, such as clinical trial delays, regulatory warnings, or even trial termination in severe cases. 

  • Financial and Operational Setbacks – A single compromised batch can cost millions in drug development and supply chain expenses. For smaller companies, this can be catastrophic since they may lack the resources to manufacture a replacement batch, forcing them to pause or cancel the trial. 


Best Practices for Maintaining -80°C Storage in Clinical Trials


To ensure investigational medicinal products remain stable and trial-ready, biotech and pharma companies should implement the following best practices:


1. Validate Cold Chain Logistics Protocols

Sponsors should use fully validated cold chain logistics protocols, including storage, handling, and transport, to minimize the chance of fluctuations. This includes using validated ultra-low temperature freezers at storage sites and distribution hubs that are equipped with backup generators in case of power failures. 


2. Advanced Temperature Monitoring Systems

Real-time temperature tracking systems should be implemented, along with integrated automated alerts and on-call personnel who are ready to respond to temperature deviations or equipment failures immediately. Temperature records should be logged continuously for regulatory compliance purposes. 


3. Post-Freeze Secondary Labeling

Many clinical trials require secondary labeling of vials after their initial storage. This can be challenging when vials are stored at -80°C, and puts batches at risk of thawing(8). To minimize this risk, validated cold-labelling processes, specifically designed for frozen drugs, should be used. 


4. Dry Ice Shipping

Dry ice shipping is commonly used for samples that require -80°C storage as it maintains biologic drug stability throughout transport. However, it does come with its own challenges, such as pressure differences (for example, during air transport) that cause variations in dry ice sublimation temperatures(9). Other possible hurdles include customs delays, which can lead to dry ice sublimation and subsequent temperature fluctuations. Therefore, shipments should be carefully monitored, biologic drugs stored in validated containers, and dry ice replenished as needed. Performing stability testing at lower temperatures can also partially mitigate this challenge(10). 


5. Partnering with Clinical Trial Supply Chain Experts

For many companies, the simplest way to ensure optimal temperature-control processes is by partnering with trusted clinical trial supply chain providers with a proven track record of success. These companies, such as PRONAV Clinical, are highly experienced in ensuring proper cold chain logistics, therefore reducing risks and improving efficiency and compliance. 


Conclusion


Ultra-low temperature storage is not just a logistical challenge – it is a non-negotiable aspect of preserving drug efficacy and safety, achieving regulatory compliance, avoiding costly delays, and, ultimately, ensuring trial success. For emerging biotech companies, early investment in validated cold storage solutions and expert cold-chain logistics advice can prevent costly setbacks, improve regulatory compliance, and significantly increase the chance of a successful clinical trial. 


Need reliable -80°C storage and clinical trial supply chain solutions? Contact PRONAV Clinical today to ensure your investigational medicinal products remain stable, compliant, and trial-ready. 


References


 
 
bottom of page