Considerations for shipping temperature-sensitive products for clinical trials

What is deemed a temperature-controlled product?

A temperature-controlled product can be split into five categories:

• Controlled Room Temperature (CRT) +15°C to +25°C
• Refrigerated +2°C to +8°C
• Frozen -15°C to -25°C
• Ultra Cold <-80°C
• Cryogenic <-140°C

Each product must be processed and stored within its specific temperature range to ensure that it remains active and safe. These temperatures are determined through vigorous stability studies during the early phases of product development and must be maintained throughout the supply chain.

How to choose the correct shipping system

Let’s look at temperature-controlled packaging. The key requirement is to maintain the product at its desired temperature for the whole duration of shipping.

• What is the duration of the product’s journey from your depot to it’s final destination (clinical site or a regional depot in another part of the world)? Does your chosen packaging maintain temperature for the full duration of transit…including a safety margin to allow for unplanned delays?
• What are the minimum/maximum numbers of packs you will be shipping? Temperature-controlled packaging comes in multiple sizes – choosing the wrong size may at best result in paying excessive courier fees to ‘ship fresh air’ and at worst could negatively impact shipper performance and result in a high number of out-of-spec shipments. Having a good idea of the size of packaging to be used can also allow for more accurate estimates of courier fees and shipper costs.
• Phase-change materials vs expanded foam shippers. While expanded foam/gel pack shippers can be suitable for short transit times and can be inexpensive, our experience is that incorporating phase change materials are the best choice for most shipments we handle. Also, these shippers have a better external dimension to payload ratio, and additional shippers’ costs can be offset by reduced courier fees.
• Single use or re-usable shippers? As the need for temperature-controlled shipments increases, so too does the environmental impact of clinical trial distribution. Temperature-controlled shippers are bulkier than uncontrolled corrugated boxes, meaning fewer shippers/journey and an increased carbon footprint. In addition, if all shippers are single use, what happens to these once a product is delivered – are they disposed of in an environmentally friendly manner? Environmental impact aside – is it reasonable to leave these to our clinical sites to dispose of. Re-usable shippers can help address this problem, but there are other considerations:
  • • Have you considered reverse logistics? How will you retrieve shippers from clinical sites? For some countries, is return to a central location even possible or is a local return point preferable?
    • Are your shippers clearly designated as re-usable, and do they include clear instructions (in a language the recipient will understand) on how to return them? Despite re-usable shippers being in common use these days, lost shippers remain a challenge.
    • Your source of re-usable shippers is also a key consideration. If you choose to buy your own shippers, bear in mind that you will need to acquire a significant safety stock to ensure you don’t run out of shippers while awaiting return of your inventory. As an alternative to ownership, Premium couriers can provide re-usable shippers, and may also manage reverse logistics, although using courier-provided shippers may tie you into using higher-priced couriers in countries where lower cost couriers provide an equally good service. While expensive, this may be preferable and more cost-effective than buying and managing your own shipper inventory. Rental arrangements, including a shipper retrieval and reconditioning service can be a good option, as they allow freedom to select your own outbound couriers, while removing the need for building you own inventory.
• For large and high value shipments, especially those crossing customs borders, we usually recommend the use of active shipping containers. These are more expensive and can be leased from most couriers but for long transit times and an increased risk of customs delays the additional cost associated with these is minimal compared to the value, or risk to continuation of supply, of the product they contain.

Regardless of the technology used, the infrastructure required to manage temperature excursions remains critical. For example, if an out-of-spec shipment is received at a clinical site, what is our process to inform the site whether the material is safe to use? How long does this process take? Who needs to be involved? How are we collecting and using the data to improve our processes and minimize the risk of this happening again? Tracking technology is advancing, but are our processes to manage newly available data keeping up?

Shipping route

Looking at your shipping route is very important as sometimes the cheapest route is not always the best as it can be the longest. While couriers should be able to advise on the best shipping routes for particular types of shipments, we recommend maintaining your own data on performance using different routes – pricing is only one factor; timeliness and the incidence (hopefully minimal) of out-of-temperature specification shipments should also be considered. We have also seen variations in the time to clear customs at different airports, even within the same country. Courier/clearing agent performance can also be inconsistent between shipping routes.

Documentation

We have selected packaging that can hold our product in the appropriate temperature range, implemented technology to track temperature and an excursion management process, and selected a route to ensure secure and timely delivery to the final destination. All of this comes to nothing if we do not include complete and accurate customs documentation with our shipment.

We’ll end this section with a tip from one of our Transportation team, who used to work as a customs officer. If the customs valuation for your shipment gives you an odd number and/or decimal points, do not be tempted to round it up! If your valuation comes to $999.93, use this value in your paperwork…and don’t be tempted round it up to $1000. Apparently, customs officers’ suspicions are aroused by round numbers, so if you round up you are increasing the likelihood of greater scrutiny, and potential delays, when your product passes through customs.

Other factors to consider

There will always be a risk of other factors arising that lie outside of your control.

• Adverse weather conditions. These can impact on the ability of packaging to hold products at the correct temperature, especially if shipper qualification was limited to ‘typical’ or ‘ideal’ conditions. It is worth checking whether your selected shipping system has been tested at extremes…although there will always be rare exceptions that nobody has tested for. Adverse weather can also lead to flight cancellations and delays – not just as a result of the ability of air traffic to safely take off and land, but also as a result of staff being unable to commute to the airport.
• Unexpected environmental conditions. Who can remember when an Icelandic volcano grounded transatlantic flights to western Europe? While this initially caused panic, the clinical supplies industry and our courier/airline partners were able to quickly develop
  alternative shipment routes to minimise the impact on this on clinical supply chain. This did add time to certain shipping routes, hence our recommendation above to select shippers that cover your planned transit time plus additional contingency time.
• Force Majeure events such as war, and industrial disputes can also impact on the reliability of airfreight.