Cold Chain is an Industry
Cold chain management has become an industry with many different players:
Freight forwarding companies (3PL or 4PL), or a logistics service provider (LSP), coordinating dedicated trucking suppliers with temperature controlled trucks and air cargo services
Container leasing companies renting out temperature controlled air cargo or ocean freight containers
Packaging companies providing custom designed transport boxes using phase change material (PCM) and vacuum insulated panels (VIP)
Solution providers for temperature monitoring using temperature data loggers, electronic temperature sensors, temperature monitoring software, and database solutions
Cold Chain is a Technology
Cold chain is also a technology using various different physical principles to maintain and document defined temperature conditions along the supply chain:
- Compressor heating and cooling
- Phase change materials (PCM)
- Insulation and vacuum insulation
- Wireless data transmission
- Database and business process management software
- Electronic temperature measurement
- Mobile IoT real-time temperature monitoring and measuring devices
What technology will I need for my supply chain?
Depending on the complexity of your supply chain, finding equipment that will best suit your needs can be challenging.
Cold Chain is a Process
Cold chain management is also a process since it requires a series of tasks to manufacture, store, transport, and monitor temperature sensitive products along the entire supply chain. Thus, every single step in the supply chain requires adherence to a defined process – often called standard operating procedures (SOP). They include guidance for:
- Using the right equipment for packaging and monitoring
- Transporting products in time
- Avoiding exposure to extreme conditions
- Following the defined release process at destination
Cold Chain is a Science
Cold chain is a science that requires understanding the chemical and biological processes driving the degradation of perishable products. Pharmaceutical products are often well-protected in primary packages. Food is very sensitive to external influences. For example:
- Food: bacteria, gases, temperature, and humidity on degradation
- Pharmaceutical products: time and temperature on the product potency (stability budget)
History of Cold Chain Monitoring
Cold chain monitoring began in the food and brewing industries. Until the early 20th century, people harvested ice blocks to keep foodstuff cool during transport and storage. The invention of the General Electric Monitor Top refrigerator in 1927 was not only the kick-start for refrigerators and freezers, but also the beginning of temperature-controlled trucks and transport containers.
Although the first vaccination was developed in 1796, and insulin was first purified in 1922, most pharmaceutical products were still chemical products, which have not been considered sensitive to temperature until a few years ago. While the cold chain grew familiar to the food industry in the 1960s and 1970 s, the pharma industry started focusing on the cold chain in the 1990s, with fast-growing markets in insulin, blood products, and vaccines. Since these are all biological products (substance derived from a living organism), the focus of the pharma cold chain industry was technologies and processes for keeping products cold or refrigerated at 2-8°C. The main term used was, therefore, “cold chain technologies” and “cold chain management.”
In 2013, the EU Good Distribution Practices (GDP) guidelines changed the scope to include all pharmaceutical products and medical devices considered to be room temperature products or products that must be stored at the controlled room temperature (CRT), between 2-25°C or 15-25°C. Since then, the term used has shifted from “cold chain logistics” to “temperature controlled logistics” – particularly in expert discussions.
The Difference Between Food Cold Chain and Pharma Cold Chain
What are the commonalities and differences between the food and the pharma cold chain? Although both product types are sensitive to temperature, there are significant differences:
- Food products are often “open” and exposed to bacteria, chemicals, and humidity. They can be sensitive to various environmental parameters. The shelf life of food products vary widely from a few days to many years depending on the product and the temperature range (frozen, fresh, or controlled). Therefore, the lengths and complexity of the supply chain has a great variance. Most food products are much more sensitive to temperature than pharmaceuticals and therefore must have shorter supply chains.
For example, if freshly cut roses are produced in India, they must reach the consumer in Europe within seven days before they fade and lose their commercial value. They are highly sensitive to temperature, fading fast at temperatures above 10°C, and cannot be frozen.
- Pharmaceutical products (commercial) are packaged to protect the product from bacteria, chemicals, and humidity. Most commercial pharmaceutical products have a shelf life of 18–36 months. They are often less sensitive to temperature compared to food products. The big challenge with most pharmaceutical products is that the quality and level of degradation is not visible to the patient; you cannot see or smell if a vaccine has been frozen, has lost its potency, or has become harmful.
The food cold chain is about preserving the commercial value. The pharma cold chain is about protecting patient safety.
Pharmaceutical Supply Chains
The supply chain can be long and complicated. Therefore, it is equally important to ensure that the right processes, people, and infrastructure are in place to handle and transport delicate products in compliance with existing regulatory policies. The following illustration shows a simple version of a drug supply chain:
The drug supply chain isn't always that simple. There are a number of different supply chains to meet the demands of a pharmaceutical business. Here are some examples:
- API Supply: Active pharmaceutical ingredients and raw materials needed for manufacturing are shipped inbound to the manufacturing facility in special bulk containers.
- Fill/Finish: A product is shipped to second GMP processing facility to encase drugs into final primary packaging.
- Clinical Trial Supply: Investigational medicinal products (IMP) are manufactured in small volumes, and clinical kits are distributed to hospitals in many different countries.
- Finished Products: After premarket approval, a product is manufactured in bulk batches and is shipped by air, sea, or road through several distribution depots, often internationally, then locally.
- Last Miles: At this point, the product is in the hands of a wholesaler, pharmacy, or hospital. This leg is the most difficult to track each product, but it is still important since the patient’s safety is the top concern.
Find out how to monitor each step of the pharmaceutical supply chain.
Overcome the unique challenges to ensure product safety and efficacy in each step of the supply chain.
Where does the responsibility end?
Market Authorization Holders (MAH) have the obligation to guarantee patient safety. But who is responsible for preventing counterfeits and temperature excursions along the entire supply chain? There are numerous risks, and the influence of the MAH decreases the deeper you go in the supply chain. Ten years ago, the answer was clear. “My responsibility ends the moment the product is delivered to my customer (e.g., the local distributor), and the quality release is given. However, over the last few years, the industry has changed.
Novel biopharmaceuticals present many challenges. Interest is growing to ship these high-value and more sensitive biological products successfully.
In new cell therapies, especially autologous therapies, the patient is at the focus of the supply chain.
With more Direct-to-Patient (DtP) clinical trials, the responsibility to monitor investigational medicinal products (IMP) is increasing. The shipper is responsible for product efficacy and patient safety as the product is carried to the clinical sites.
Get your complete guide to GDP.
Download a summary of everything you need to know about GDP guidelines as they relate to your temperature monitoring.