The safety of a pharmaceutical product, effectiveness of a patient's treatment regimen or success of a clinical trial often relies upon how well we manage storage and transit temperature across the supply chain.

The efficacy of today’s higher value and structurally complex drugs can be destroyed through a single cold-chain break; the integrity of controlled room temperature products can be impacted through inconsistent environmental conditions during distribution; while a weak link in the management of temperature sensitive clinical trial materials can impact study outcomes and lead to extremely costly delays in bringing new products to market.

These challenges as well as the globalization of supply chains and increased regulatory scrutiny which can reach across borders, makes temperature management throughout the pharmaceutical industry more important than ever before.

Shifting market dynamics

One of the most significant changes within the pharmaceutical industry in recent years is the evolution of drug portfolios. Many manufacturers are moving away from small or single molecule/chemical pharmaceuticals towards more structurally complex biotechnology drugs. Biologics accounted for 29 percent of branded global pharmaceutical sales in 2014, up from 10 percent in 2000, while consumption of specialty drugs increased by 7 per cent in the United States in 2015. Biologic pharmaceutical products, often derived from living cells and used in targeted or specialized treatments, have much stricter handling requirements and failure to adhere to these requirements at any point in the drug’s lifecycle can impact product quality and efficacy, put patients at risk or result in significant product waste and supply chain disruption. 20% of temperature sensitive products are damaged during distribution due to a break in the cold chain – a very worrying statistic when you consider 7 of the world’s top 10 selling drugs will require cold chain management between two and eight degrees Celsius by 2018 .

Clinical trial management

These shifting market dynamics do not only impact the storage and distribution of finished products, they also impact clinical trial logistics. Large molecule drugs are generally more sensitive to the external environment than small molecule drugs meaning any break in the cold chain can compromise the drug or sample integrity, spoil an experimental protocol, breach security or delay shipments. These challenges can add significant cost to the trial and lead to study and drug approval delays. At the same time, the high cost of trialing more structurally complex biotechnology drugs mean clinical trial supply chains are under pressure to become leaner, and more agile. This results in lower up front drug production to support the trial and more intermittent sub-batches. Waste due to temperature excursions can therefore easily lead to stock-outs of required products, an inability to supply enrolled patients or re-supply issues for patients already under treatment in a randomized study. This could delay studies, pushing back the introduction of a new treatment or drug for patients and costing the trial sponsor millions of dollars in R&D costs as well as potential sales.

Controlled room temperature

Adding to this complexity is the increased focus on controlled room temperature (CRT) products requiring storage conditions between 15 and 25 degrees Celsius. Historically, CRT products could be shipped with standard packaging, using standard logistics processes but recent developments in the global regulatory landscape mean that CRT products now also require strict adherence to a temperature-controlled supply chain.

The 2013 European Union update of its Good Distribution Practice (GDP) Guidelines made specific reference to the storage of products in accordance with packaging label specifications. This has resulted in expanded oversight for CRT drugs and brings approximately 80% of all finished pharmaceutical products under strict requirements for temperature control. The EU Guidelines set new benchmarks for other international GDP standards with countries and regulatory bodies around the world adopting them in various forms. This new guidance has therefore shaped the way the industry manages CRT products and ongoing investment is being made in CRT solutions such as air conditioned fleets and storage facilities in many markets around the world.

Transit guidelines

The updated EU guidelines also provided more specific requirements on how products should be stored in transit, extending the requirement to store products within the temperature range specified on the packaging to transportation as well as storage. This has had a significant impact on the industry and a number of international transit lane mapping studies have been carried out to pinpoint weak spots across the supply chain. These studies show a number of risk areas, particularly the time that airfreight spends waiting on the tarmac or sea freight spends waiting at the dock prior to loading and after unloading.

Some markets in Asia are taking steps to manage this risk. Singapore, for example, has established a dedicated cold chain facility at Changi airport. Temperature-sensitive products are unloaded into this facility within 45 minutes of the plane landing to ensure that their temperature integrity is maintained.

The industry is also investing in new solutions to mitigate the risk of temperature excursions. Zuellig Pharma’s eZCooler packaging system is one example of this. It extends the holding time of temperature sensitive products to five days, versus two days with traditional systems. In the hot, often temperamental climates in South East Asia, this system has a big role to play in helping to ensure temperature-sensitive products reach their destination in good condition, particularly in remote, rural areas.

Compliance

Regulators are placing a much higher level of scrutiny on quality systems and processes and temperature management is one key element of this. Regulatory bodies require proof that all drugs and biological components have been distributed within the required temperature range – meaning all processes and sub processes need to be validated to ensure there has been no negative impact on the safety, efficacy or quality of a product.

To do this, monitoring and reporting technology such as temperature monitors, sensors and track and trace systems are used. Much of this reporting is currently provided on a historical basis, at the end of a journey or delivery, but there is a growing trend to real time monitoring which will provide alerts if the temperature deviates beyond the safe range.

Companies need to invest in more sophisticated supply chain infrastructure to comply with new regulations and while this can be costly, the cost of non-compliance is likely to be much higher. A single consignment of drugs being distributed can be worth millions of dollars and a cold chain break can mean an entire shipment needs to be written off while a recalled batch of drugs due to temperature excursion can lead to significant reputational damage or regulatory scrutiny.

Outlook

The pharmaceutical industry is going through a period of rapid change. The evolution of drug portfolios, increased regulatory attention of a greater range of products and significant costs associated with temperature excursions mean temperature management will only continue to become more important. Globally, the industry is set to spend more than $16 billion on temperature management initiatives by 2020 and I believe this investment will only continue to increase as the importance of temperature management grows.