The task of ensuring clinical supplies are fit for purpose begins right at source and ends at the point of use, and a key element is making sure they are not exposed to excess temperatures. Temperature monitoring technology has advanced significantly in recent years, and is now playing a major part in maintaining product integrity. Philip Chou of Elan Pharmaceuticals tells us how pharmaceutical companies and their suppliers can ensure temperature integrity through technology and procedures.
The development of new drug treatments can be a long and arduous task even before they arrive at the clinical trial stage. When trials start, a new set of challenges arise and one of the biggest is ensuring that products arrive safely and in the right condition. One of the key factors in that process is maintaining temperature integrity, which is why the industry invests heavily in the cold chain, even before a drug has properly been developed.
The issue of temperature monitoring has long been one that has taxed the minds of the pharmaceutical sector. A survey by IQPC in 2011 revealed that, in no particular order, temperature monitoring devices, temperature controlled shipping containers, and track and trace technology were the top three needs in the pharmaceutical supply chain. The figure shows that even in today’s technology savvy, increasingly innovative world, temperature control is, and will continue to be, an issue.
But it is also important to acknowledge that it is just one essential component in a wider mix of factors. There are myriad technologies and practices that have been developed to make the cold chain as effective as possible. Technology developers have worked hard to create temperature monitoring tools that not only give precise readouts on temperature changes during transit, but also create alarms if specified parameters are exceeded. These tools have made it easier to ship clinical supplies with more limited temperature ranges, and they represent the biggest step forward in shipping capability.
Nevertheless, there is still more work to be done. Many of the innovative products undergoing trials are increasingly sensitive to temperature changes, so tools and processes must continue to evolve.
"There are many challenges but largely it is the particular temperature range that a product has that determines how easy or difficult it is to manage the cold chain," says Philip Chou, associate director, clinical supplies at Elan Pharmaceuticals. "Some products may have a narrow range, which makes it difficult to manage. The key is to give a product the broadest range of parameters possible.
"That means not only temperature range parameters, but also excursion parameters. What are the upper and lower limits, and for how long can a product go outside its defined temperature range? Those are the questions that need to be asked."
Chou’s job involves managing planning, labelling, packaging and distribution of investigational medicinal product for phase I to phase III clinical trials run by Elan. As a result, he well knows the importance of maintaining the integrity of the cold chain. He also knows from experience that no matter how much care is taken in designing a shipping solution, there will be occasions when these limits will not always be adhered to during the transit phase.
"There are technologies and procedural controls for materials in transit, but excursions do happen," he says. "After all, shipping is always subject to the weather, which we can’t control, so that is one factor that may cause problems. In clinical shipments, excursions are relatively common, but they are generally not too bad. Clinical supplies need customised shipping solutions as we are not shipping the same materials using the same methods each time.
"You can generally use off-the-shelf packaging products, but a lot depends on the design of the shipping profile. More work is definitely needed on processes, as there are always things that can be improved."
RFID technology has helped to dramatically change the focus of the cold chain over the past few decades but it is more recently that they have really left their mark. Some of the latest temperature monitoring tags enable the transfer of critical data on temperature status and whether the predetermined parameters have been breached to be wirelessly collected. LED technology is now also adding to the already obvious benefits of RFID in the cold chain, making the process of collecting data, assessing a product’s integrity and protecting against the threat of temperature excursion easier.
Previously, tools such as USB data loggers and chemical indicators had been, and still are to a great extent, been employed to gauge and log the stability of a product in transit.
Flexible options
The more a company can broaden the temperature range for any given shipment, the more flexibility it has in defining the shipping process. A broader range gives it more options in terms of which shippers they can choose.
"In some cases, they might be able to use a general courier company instead of a specialist shipper," says Chou.
Nevertheless, it is not always possible to give a broad temperature range for an individual product, in which case companies will have to look at technologies, such as RFID, and processes to monitor temperatures en route, or to heat or cool that material while it is in transit.
"The technology for temperature monitoring is quite good and reasonably priced," explains Chou. "It has really advanced in the last ten years, especially with the arrival of digital technologies to replace temperature strips, which were never easy to use. These technologies can be programmed with excursion parameters for both temperature and duration, so can raise an alarm if both of these parameters are breached.
"That makes managing the process much more efficient. Also, you can log near misses to help with the design of better parameters and processes for the future."
If there is any doubt about whether the right parameters have been achieved then companies can always do test shipments to make adjustments in the shipping process for a given material, though this does have an impact on costs.
"The most important thing is to know your shipment and understand your needs in order to choose the right packaging solution and shipper. That allows you to focus more on costs," says Chou.
Re-examining room temperature
If a product is specified for transit at room temperature, it is easy to assume that relatively little consideration need be given to temperature excursions, and products with such parameters often have no monitoring capability. Chou, however, advises against this, and it is certainly not the attitude of regulators.
"Room temperature is like any other temperature range, so it needs to be maintained and monitored," he says. "Increasingly, you have to show regulators that room temperature was maintained throughout transit. Previously, the shipping of room temperature products was handled in a very crude and off-the-cuff way using frozen gel packs and standard packaging. Now, there are more controlled solutions, even though the room temperature range is relatively broad.
"We have sent shipments with temperature monitors on the outside and the inside and we have seen a broad range of temperatures recorded, especially when different modes of transport are used. For instance, there are factors at an airport that may be hard to control, such as whether a product is left for too long near a hot engine or in an area in a cargo bay that is too cold.
"Regulators now want proof that temperature integrity has been maintained, even for room temperature parameters, and we did not see that two years ago. Also, you can’t assume stability just because a product is solid, like a pill."
Foresight and planning
However important temperature monitoring is to an effective cold chain, for Chou, another essential way of optimising the cold chain – in terms of cost and efficiency – is to know as much as possible about the requirements of each shipment.
"If it is an irreplaceable shipment, then every choice about the shipping process must reflect that," he says. "You probably need to choose a more expensive shipper with high levels of service, and you may also need temperature-monitoring redundancy with more multiple systems so that one can fail.
For the most part, Chou feels that pharmaceutical companies and the shippers they use are aware of the challenges that exist in the cold chain for clinical supplies and have worked hard to overcome them.
"People are looking at the issue of temperature integrity. Shippers have specialised packaging solutions," he says. "There are five or six shippers that have capability in this area and there are also niche providers that can be used to reach some parts of the world. The heavy lifting has been done, but every year there are still advances made in shipping and monitoring technology. Systems are becoming smaller, lighter and cheaper, and they can help to keep a product within a defined temperature range for longer.
"Shipping processes have improved dramatically, even in the last five years, and they are still evolving. As the technology improves, cost goes down and it is now possible to ship materials that could not have been shipped before because the temperature range was too narrow.
"Shippers are always pushing the envelope, and that is necessary as the molecules used in clinical trials are often less stable and smaller and they need to get to people quicker. That is why we need transport and logistics solutions to keep advancing."
Nevertheless, for Chou, the onus of improving shipping processes must not fall entirely on the shippers. The companies behind the products being shipped can do a great deal to help themselves by optimising their requirements in advance.
"It is not like you can pick up the phone to FedEx and say you have a shipment of clinical supplies that needs to go tomorrow. Companies need to think ahead," he advises.