Cold Chain Logistics and its Challenges

Elements of Cold Chain Logistics

There are a number of different supply chains to meet the demands of a pharmaceutical business. They include: 

• API Supply: Active Pharmaceutical Ingredients and raw materials needed for manufacturing are shipped inbound to the manufacturing facility in special bulk containers.
• GMP Fill/Finish: A second GMP processing facility to encase drug into final primary packaging.
• Clinical Trial Supply: Investigational Medicinal Products (IMPs) manufactured in small volumes and clinical kits are distributed to hospitals in many different countries.
• Finished Products: After market approval, a product is manufactured in bulk batches and shipped by air, sea or road through several distribution depots often internationally, then locally. 
• Last Miles: After a product is sold, it's in the hands of a wholesaler, pharmacy or hospital. This leg is most difficult to track each product. Patient safety is s top concern. 

In each supply chain, there are inherent risks depending on your choice of transport mode, packaging equipment and partners. 

The Pharma Supply Chain

This supply chain can have up to seven different storage steps and between each “storage step”, the goods need transportation with road, air or ocean. The following illustration shows a simple version of a drug supply chain:

Comparing 5  Cold Chain Risks Using
Active or Passive Systems

During a transport, excursions from the promised transport conditions can and will happen. Why?

From experience of millions of pharma shipments analysed in our database, we know that less than 10% of all cases, a true temperature alert (excursion outside defined shipping conditions) is found. Typically, half of the cases are caused by late stop or other mistakes that happen at destination – which could be considered false excursions.  

To know the risks, it is important to understand the cold chain logistics equipment:

Temperature Monitoring of the
“Finished Product Supply Chain”

The problem of counterfeit has received a lot of attention in the past few years. The EU's Falsified Medicines Directive (FMD) is defining serialization as a prerequisite for market authorizations since February 2019. Due to this initiative, each single product unit must carry a unique serial number as standardized barcode referring additional information (such as batch, production date etc.).

During aggregation, the single product boxes are then aggregated to higher levels of packaging (product-box -> sales-unit -> pallet -> delivery unit) again printed as barcodes on the respective level and also captured in a database. A central serialization database – such as tracelink, now knows exactly, which items belong where.

Challenges with Track & Trace

GS1, a non-profit organization that developed and maintains global standards for business communication, even goes a step further and wants to track those aggregated units (e.g. sales-units) along the supply chain and exactly track where the box has been where. If we would in addition also add the respective temperature measurement row into this “global serialization-aggregation-track&trace-database”, we would have the crystal ball and could at any time in the supply chain check this database:

• Is the product in my hand an original (non-counterfeit) product?
• Is the product in my hand o.k. to use (is the total time out of refrigeration this product has experienced so far, inside the defined stability budget)?

The problem with this crystal ball: it is still just vision, and considering all the interfaces that will be needed between all the different ERP-system of each party of the supply chain, implementation will be very complex and result in high cost for each single-product unit.

The Ultimate Dream –
A Box Level Real-Time Device

The ultimate dream solving all the mentioned challenges would be:

• A device on box/kit/vial-level staying there for the entire lifecycle (e.g. 3 years), which can measure temperature and manage stability budget end-to-end, and transmit this data wirelessly to a cloud database (therefore also knows at all times where it is geographically).
• Then the cloud database would alarm in case of deviation, know whose fault it was, even prevent deviations by pro-active interventions, and it could further automate release at each handover-point, and even automatically manage stock at the hospitals/pharmacies.

Disney said, “If you can dream it, you can do it”. But unfortunately today a box level real-time device is technically not possible:

• Although Mobile-IoT networks are developing fast, the communication chips as well as the roaming cost are still too expensive to be applied on a chip level
• The Mobile-IoT communication chips still need a large amount of energy to communicate with nearby public antenna networks. If we would try to cover a lifespan of 2+ years, we would need a huge battery pack
• And such a device would never fit on box/kit/vial-level (LPWAN communication chip, Mobile-IoT antenna, large battery-pack)

What we see is an increasing discussion around gateway concepts. So a larger unit (e.g. box) is equipped with an IoT-gateway which is communicating via Bluetooth to mini-sensors sitting on vials in the same box.