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How to Safely Ship Investigational Medicinal Products on Dry Ice: Best Practices and Common Pitfalls

  • PRONAV
  • Jul 23
  • 8 min read

The effective transport of Investigational Medicinal Products (IMPs) requires careful management to ensure the integrity of the product. IMPs can include highly temperature-sensitive products, such as biologics, cell therapies, and mRNA-based drugs, which at higher temperatures, can become unstable, with components undergoing protein denaturation, RNA degradation, and loss of efficacy1–3. Therefore, ultra-low temperature-controlled shipping (-80°C) is essential to ensure stability when IMPs are transported. 


Dry ice shipping is a common solution for transporting IMPs as it maintains ultra-low temperatures without requiring power, making it a cheap and effective option. However, improper handling of IMPs packed in dry ice can result in temperature excursions (thereby risking product integrity), safety hazards, and regulatory non-compliance. In one study, 44.6% of survey respondents had experienced issues with temperature deviations, with 37% of these reporting a deviation of up to 4°C, and 21% between 4-8°C4. The consequences of these temperature excursions can result in a loss of the product and disruption in patient supply, highlighting the importance of precise handling during product transit. 


The Complexities of Shipping IMPs on Dry Ice


Sublimation and Temperature Control

Over time, dry ice absorbs heat energy and sublimates (turns straight from a solid to a gas). It will only remain solid for a certain period of time, so precise planning is required for product transit time and/or replenishment time. Dry ice sublimates approximately 8% every 24 hours5, however, certain factors can alter the rate of sublimation including:


  • High ambient temperatures

  • Increased surface area

  • High air circulation

  • Poor insulation

  • Air pressure – at lower pressures, dry ice can sublimate at temperatures lower than -90°C, potentially causing damage to IMPs6. 


As discussed in more detail below, care must be taken to ensure that sufficient dry ice is present and that it is packed properly to ensure that ultra-low temperatures are maintained throughout the journey. Consideration should also be given to the effect of different airline cabin pressures.


Transport Regulatory Compliance

Dry ice shipping poses significant dangers, including asphyxiation, poisoning, and explosion. As dry ice sublimates, it releases CO2 gas. This displaces oxygen in the surrounding enclosed space and can result in lower cognitive performance, difficulty in breathing, and potential death5,7. 


Dry ice can also pose an explosion risk if stored in a sealed container. As dry ice sublimates (changes directly from solid to gas), it produces a large volume of carbon dioxide gas. If this gas is trapped within a sealed container, the pressure build-up can cause the container to rupture or explode. 


As a result, dry ice is classified as a hazardous material. Product transiting in dry ice packaging must comply with IATA (International Air Transport Association) dangerous goods regulations for air transport and DOT (Department of Transportation) and ADR (European Agreement) for road transport. Compliance with these regulations poses further complexities than traditional shipping.


Transit Time and Route Planning

During long-distance and international shipments, the product has to remain frozen for a longer period of time. These transports require custom-designed transit plans to ensure that sufficient dry ice is used and that provision is made for dry ice replenishment if needed. Ensuring the chosen courier has immediate access to dry ice and/ or -80°C storage capacity at each of its hubs is crucial in order to accommodate shipping interruptions, which will inevitably arise from time to time. Where possible, it is highly recommended that route proving using dummy material is performed in advance of shipment of the actual product.


Dry Ice Shipping


Best Practices for Safe and Compliant Dry Ice Shipments


The following factors must be considered for the effective, safe, and compliant transport of IMPs using dry ice:


  1. Choosing the correct packaging materials

Validated insulated containers, which have been designed and tested to minimize temperature excursions, should be used. The payload should be fully immersed in the dry ice with adequate coverage all around. 


If CO2 vapor concentration adjacent to the dry ice is lowered below 100% then the dry ice will sublimate at decreasing temperatures as the vapor concentration lowers, potentially reaching as low as -93°C6. This lower temperature can affect the integrity of the seal between vial stoppers and the vial necks, with potential implications for the maintenance of sterility. To ameliorate the potential for low temperatures, the CO2 concentration in the vapor space in the container should be maintained as close to 100% as possible6. This can be achieved by placing LDPE liners in the containers, which, after filling with the payload and dry ice, are loosely folded over the top of the dry ice, providing an overall envelope. This tends to contain the CO2 vapour concentration at higher levels. Note: these liners should never be sealed tightly.


The containers can also be filled with insulating material, such as styrofoam, to reduce the amount of air between the dry ice and the lid of the container. Containers must also provide ventilation to prevent a build-up in pressure and a potential explosion8 caused by the dry ice sublimation into CO2 gas.


Dry Ice Shipping Boxes

  1. Pre-chilling the container prior to packing

IMP products can experience a temperature shock when transferred to ultra-low temperatures. Pre-cooling the payload container prior to packaging in dry ice can prevent this temperature shock and potential damage to the IMP.


  1. Calculating the correct amount of dry ice

Dry ice sublimates at a rate of approximately 8% every 24 hours; the amount needed for a specific transit time must be calculated accordingly. Certain conditions can increase rates of sublimation, including ambient temperatures and changes in air pressure (such as those experienced in air transport); these must be factored into the calculations. Planning for a mid-shipment dry ice replenishment may be necessary if the shipment is long-distance. This should be performed by a trusted partner to ensure that the dry ice is replenished without large temperature fluctuations or harm to the product, and that the product is handled and repackaged correctly. 


  1. Choosing the correct airline

Changes in air pressure can affect dry ice sublimation, causing temperature drops at lower air pressure levels. Commercial passenger aircraft have typical cabin pressures of 10-12 psi, i.e., slightly below normal atmospheric pressure. Whilst this can cause dry ice shipments in the cargo hold (held at the same pressure) to sublime at slightly lower temperatures, their temperatures usually remain well within the specification limits for the product. However, lower cabin pressures of 6-8 psi, as sometimes used in older dedicated cargo aircraft, can cause the sublimation temperature to fall to less than -90°C, especially if the CO2 vapour concentration close to the dry ice is not well maintained. 


To minimize the potential product impact of lower temperatures, it is recommended that the product being transported has been tested at these lower temperatures9. If the stability data does not exist, or the product fails stability tests at these lower temperatures, an alternative shipping route must be planned.


  1. Implementing continuous temperature monitoring

Loss of temperature data and/or temperature excursions are the most common causes of deviations during transportation. These can result in potential delays in product delivery to the patient while the issue is investigated and the impact on the quality of the product is assessed, or possible product loss if it cannot be used. 


It is essential to use temperature data loggers to provide evidence that the cold chain conditions were maintained during transport, and this should be reviewed immediately upon arrival of the product. It is also important to provide clear instructions on how to check and download the data for the person receiving the product, along with information on how to report temperature excursions. 


For particularly critical shipments, real-time temperature and location tracking systems complete with alert systems should be considered. By monitoring the temperature and location in real time, the necessary preventive actions can be taken in advance of temperature limits being reached (for example, dry ice replenishment).



  1. Training staff on safe handling procedures

Dry ice is a hazardous substance with the potential to cause severe cold burns, asphyxiation, and explosions. Safety protocols must be in place to provide standard operating procedures and risk assessments, and teams must be trained on these to ensure correct handling, storage, and ventilation.


Common Pitfalls to Avoid


  • Underestimating dry ice requirements – Incorrectly calculating the amount of dry ice necessary could result in a rise in temperature and subsequent degradation or damage to the IMP.


  • Failure to plan for delays – Delays in transport are common, with 18% of loss or damage to pharmaceuticals in transit occurring due to delays4. Therefore, it is essential to factor delays, such as customs clearance or weather-related issues, into calculations of dry ice sublimation to ensure that sufficient dry ice remains for the duration of the transport. Regulatory agencies, such as the FDA, may need to pre-approve the transport of certain materials, including biological drugs. Pre-approval, known as “Greenlighting”, will prevent delays or issues arising from customs clearance. However, obtaining pre-approval is a complicated process requiring specialist knowledge; an experienced third-party partner will be able to assist with this.


  • Improper labeling and documentation – Shipments involving dry ice are classed as hazardous, so they require hazardous materials labeling and transport permits. Failure to comply with the necessary requirements can result in significant delays, potential damage to the products being shipped, and issues with clinical trial logistics.


  • Inadequate packaging that leads to temperature excursions – Temperature fluctuations can occur if non-validated containers or improper insulation are used.


Conclusion: Ensuring IMP Integrity with Proper Dry Ice Shipping Practices


The use of dry ice is essential in maintaining the ultra-low temperatures required for transporting IMPs. However, the planning and preparation for transport, in addition to the transport itself, must be handled with care and precision. Validated packaging, regulatory compliance, temperature monitoring, and careful calculations of dry ice sublimation are essential in preventing temperature excursions and ensuring the viability of the product.


Experienced clinical supply chain partners, such as PRONAV Clinical, can offer emerging biotech companies the necessary assistance and knowledge to ensure seamless and compliant dry ice shipments.


Need expert support for shipping IMPs on dry ice? Contact PRONAV Clinical today to ensure your investigational products reach trial sites safely and on time.


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