Freezing out fault

Picture the scene: Frankfurt airport on a pleasant summer afternoon. The outside temperature is 20 degrees Celsius. Sitting on the tarmac is an LD3 aircraft container. It has been resting there for two hours and the temperature inside it has now risen to 76 degrees Celsius. This is bad news if it contains temperature-sensitive goods such as pharmaceutical or life science products bound for Asia.

The complexities of a successful cold chain are not often recognised or understood by the end user, whether this is a healthcare professional, scientific researcher or medical patient. However, the processes in place are vital for an increasingly global marketplace, facilitating trade and at the same time ensuring product integrity and safety.

Of course, this does not mean that cold chain is merely a chilly set of logistics activities. Cold chain is a temperature-controlled supply chain entailing an uninterrupted series of storage and distribution activities which maintain a given temperature range.

And, although this may conjure images of refrigerated trucks delivering goods to icy storage facilities, cold chain excellence depends on much more than infrastructure. Why has cold chain excellence become an important deliverable for service providers in the logistics industry, and a must for drug and pharma companies around the world?

Despite the economic downturn, the life sciences and healthcare sectors continue to grow, whether it be by producing medicines to treat the common cold, developing tests for an epidemic such as H1N1 flu, or engaging in R&D to find a cure for cancer. As the industry evolves, it continues to expand globally. Today's pharmaceutical footprint looks very different from the one it had a decade ago.

There is a variety of reasons for this. Some of it is driven by the sourcing of Active Pharmaceutical Ingredients (API) in new markets around the world. Key ingredients that were once obtained in Europe are now also being purchased from suppliers in other regions, like central Asia. This adds complexity to the supply chain at its outset. 

Mergers and acquisitions are also increasing globalisation, especially as pharmaceutical companies consolidate manufacturing bases. Supply chains are changing as products are travelling greater distances, and through a more diverse range of climates, often with great diversity in the locations of the researchers, clinicians, manufacturers and patients. A product that starts its journey in a climate that requires protection from heat may end up in a climate where it needs protection from freezing.

In addition, there are the associated legal requirements to be taken into account. Products must meet an international patchwork of regulations relating to transport and handling. Plus, new or revised regulations that pertain to the required temperature range of life science and healthcare products, such as those set by the US Food and Drug Administration (FDA) also require service providers to respond with cold chain solutions.

Demand
Further, cold chain solutions are more in demand because of the changing profile of pharmaceutical products, such as the increase in new biotech drugs. These have a larger molecular structure and, as a result, are more sensitive to temperature and humidity.

Of course, products that are temperature sensitive, or classified as high-risk, include much more than sophisticated medicines. Vaccines, insulin, fatty-based suppositories and eye drops are all classified as 'high-risk,' and require consistent temperature control as they move along the supply chain.

Consequences
Cold chain carries greater risk and consequence than a traditional supply chain. The main concern with cold chain is the possibility of temperature excursion, when the required temperature zone for a product is exceeded. From release by manufacturer to arrival on the market, pharmaceutical products have a certain tolerance for temperature excursion. However, if the temperature excursions during the transport period cumulatively exceed that designated by R&D Quality, then the product could become spoiled and potentially cause the customer significant expense. At the very least, it will require a quality check, which in turn causes a delay in the supply chain. Ultimately, all the measures are designed to  protect the health of the end user.

The risks caused by temperature excursions are serious for pharmaceutical products. Medicines contain both active ingredients and filler. Exposed to high temperatures, these can separate with potentially dangerous consequences. Physical changes to products include the separation of emulsion systems or sedimentation of active ingredients leading to higher concentrations of the latter. Products could also lose volatile components such as chloroform. Changes in crystalline structure and chemical changes, such as an increased rate of degradation, can result in shorter shelf lives. Temperature excursions can also cause a greater rate of interaction between the product and its packaging.

Efficacy
What does this mean for end consumers and the customers of service providers? Temperature excursions could affect the efficacy of a product, nullifying its intended effect. There is also a possibility that a pharmaceutical product that has been exposed to unsuitable temperatures could become harmful to patients.

For the manufacturer, temperature excursions could mean having to dispose of products and face supply shortages. In extreme cases, there could be legal repercussions such as fines, licence suspensions, site closures, damage to corporate image and health problems.

This makes third-party logistics providers responsible for developing a culture of cold chain excellence, where they have a deep understanding of the product and how to manage it as it moves along the distribution line. Anything less than this will fail to satisfy the customer and, worse, to protect the patient. However, as a temperature-sensitive product moves from the manufacturer to the market, there are numerous possibilities for things to go wrong.

Maintaining pharmaceutical product integrity throughout the supply chain is no small challenge. The greatest risk of temperature excursions occur at the several handover points in the chain. As a product moves from shipper to forwarder to an airline or ocean carrier and then to a customs environment and back into a trucking environment, there are many opportunities for temperature deviation. As shown by the example of the container at Frankfurt airport, handovers create gaps in the cold chain.

Even the position of the product in the cargo hold of a commercial airline can affect its integrity. This also varies between different types of airplane.

People and processes
The logistics industry's approach to creating a culture of cold chain excellence involves having the right infrastructure in place, such as cold storage areas where pharmaceutical products are separated from dry chain goods. But it also involves well-tested processes and the key to success in any business activity: dedicated and knowledgeable people.

DHL is creating Life Science Competence Centres (LSCC) around the world in order to ensure the continued provision of world-class cold chain services. Centres have been created that include sophisticated cold-chain infrastructure and core teams of industry experts responsible for developing bespoke products and solutions for healthcare clients. In addition to providing the warehouses and vehicles to store and transport cold chain goods, the LSCC are staffed by people who understand the life science sector and temperature control and who have the knowledge to do everything from dry ice calculations to managing packaging solutions.

The importance of the cold chain requires pharmaceutical companies to place a tremendous amount of trust in their logistics service providers. Therefore, they need to work with a service provider that has the competence to manage the entire supply chain. For example, we have identified the customs environment as a risky handover point for temperature-sensitive goods. At some ports, customs have cold storage spaces, while at others they do not. If a shipment of pharmaceutical products is held up in a customs environment without cold storage facilities, there is a real risk that they will become compromised.

While having the right infrastructure is important, this scenario demonstrates that it is essential for a logistics service provider to have the right knowledge and processes in place to help avoid such an eventuality.

DHL has over 4,000 people worldwide, including qualified pharmacists, dedicated to the industry sector. These people are connected to the company's life science experts through Global Customer Solutions (GCS). This dedicated customer management organisation works for DHL's top 100 global customers, designing and deploying tailored logistics services across a customer's entire supply chain.

Such a structure is a major investment, but it pays off when it comes to managing the complexities of a cold chain.

Ultimately, the goal of the logistics service provider is to get the products to the right place in the right condition and on time. Only by taking a holistic view of the chain, constantly monitoring for potential exposures and closing gaps, can this be achieved.

The logistics service provider must make its customer's problems its own. While this requires investing in the latest technologies and infrastructure, the largest investment is in cultivating the best processes and training competent staff.

The Author
Angelos Orfanos is global head of life sciences & healthcare at DHL

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