Transporting pharmaceutical products is always an exercise in risk management because of the high standards of safety required, and major investment has been made in technology and processes to preserve the integrity of the cold chain. However, as clinical trials and drug sales spread into developing markets, these are being put to the test.

"There are two strands to this, the first is making sure that the quality of the product is maintained throughout its life," says Henryk Junker, quality assurance manager at Allergan R&D Europe. "For example, in clinical trials, the high-risk piece is in transport from the GMP facility to the clinical facility.

"The second strand is ensuring that patients are safe. In trials, this also means maintaining the integrity of your study, and there could be an impact on your company if there is any failure. If it is a clinical trial, then you might have to repeat the study, which can be very expensive.

"You must have the right controls in place. In emerging markets, the industry has come a long way in the last 20 years. Back then, the risks were much higher, but the people handling the products have become much more sophisticated."

European GDP update

Throughout the cold chain, the onus is on pharmaceutical companies to assess their partners and put in place thorough processes for measuring quality, if only to meet the demands of regulators.

"In the cold chain, you need to generate stability data, especially if you want to get a product to clinical trials."

In Europe, an updated version of guidelines on good distribution practice (GDP) was published in March this year and will come into force in September. The update highlights the importance of maintaining the quality and integrity of medicinal products throughout the supply chain, from the manufacturer to the patient, and outlines the responsibilities, processes and risk-management principles of wholesale activities, as well as setting out the requirements for suitable documentation and competent personnel, adequate premises and equipment to ensure proper storage and distribution.

"You have to pick the right partners and you must be able to get visibility of the supply chain," says Junker. "The regulatory landscape is changing in light of concerns about counterfeiting in the industry, so regulators in the US and Europe are saying that we need to have the right controls. Updates to the GDP have addressed this, and the buck stops with the pharmaceutical companies. Ultimately, it is their decision who they work with and what processes are used.

"To get visibility of the supply chain, regulators have pushed us to go out and do audits, though this is of limited value. All it gives you is a snapshot in time. But a quality technical agreement lays out who is responsible for what, and defines the expectations on controls – particularly temperature controls. In the cold chain, you need to generate stability data, especially if you want to get a product to clinical trials. You need to build up data on the limits of your product in each case."

Safe supply chain: close contact required

Pharma companies have become wise to the idea that they must put in significant effort up front to get the necessary data and define the parameters for each product shipped. This involves no small amount of time and effort, but in the long run, it may prove less costly, in monetary and reputational terms, than a failure of the cold chain and the consequent damage to a clinical trial or product launch.

To illustrate the importance of doing the groundwork and checking the claims of shipping partners, Junker points to another industry where safety and cost are prime concerns – space exploration. The Challenger space shuttle disaster, in which the failure of ‘O’ rings on the booster rockets caused a fatal explosion, has been examined in great detail in the intervening years and provides lessons for anyone concerned with preserving the lives of others.

"Pharma companies must put in significant effort up front to get the necessary data and define the parameters for each product shipped."

"The suppliers of the ‘O’ rings claimed that they could go as low as -70°C but, when they were tested after the event, they did not perform to that level," he explains. "My point is that you must prove the claims about temperature in the cold chain and generate the data on acceptable excursions, or it could have a big impact on your trial or your product. Most companies do that. It is about being involved with the people that move your products to clinical sites.

"You have to work with your couriers and your depots and talk to them regularly. You have to deal with issues as they arise and not put it off until later, especially in emerging markets. You have to have a partnership, not just a contract. Service is very important and you need to choose someone who has knowledge of the countries you are going into. They need to understand many factors, including customs issues and local regulations. They should also be able to advise you, rather than just acting on your instructions."

For Junker, the key is planning. Defining cold chain processes that suit the products being shipped and the market to which they are destined not only minimises risks to the integrity of the product, but also gives scope to address cost issues in more detail.

"Planning is one of the most critical parts of the process. You have to think through the products, the volumes you are shipping and the destinations in order to get a safe chain of custody. It can also help to bring costs down, if you know where your patients are. I’m a quality person, but it is still important to me to plan the most effective supply chain to minimise costs.

"One of the issues is whether to use direct shipment or depots. With direct shipment, the cost goes up as the distances get longer, so bulk shipping to a depot that deals with onward shipment may be a cheaper option if there is a big volume of product. Another issue is the choice of shipper and whether to choose a single use option or a re-useable option that incurs the additional cost of shipping it back from its destination."

Shipping drugs to emerging markets

The performance of shipping partners in emerging markets is improving all the time and many have built up a solid track record.

"Shippers are much more stable than they were even five years ago," says Junker. "In emerging markets, there is now enough data to show that you can ship to, say, China, without any temperature excursions, though you still have to have a contingency plan.

"There has been improvement across all regions, though there are still variations. In China, if you are shipping to a major city like Beijing or Shanghai, then the process is straightforward, but if it is to a less-developed destination, the process becomes more challenging. If you are looking for a naïve population for a trial, if you may need to extend your reach."

"We always monitor drugs to the site to look at factors like shipping times, proof of delivery and temperatures in transit."

Shipping to emerging markets may bring more risk to the cold chain, whether it is in the form of underdeveloped infrastructure, political risk or regulatory differences, but an appreciation of the requirements of the global pharma industry among shipping partners means that those risks are often mitigated as much as is possible.

"We always monitor drugs to the site to look at factors like shipping times, proof of delivery and temperatures in transit," explains Junker. "You need to understand the nuances of each delivery process, though you can pool the knowledge you have gained from previous shipments so that you don’t have to come up with a bespoke solution every time. But you still need the right local knowledge and a shipper with a good track record.

"No one wants to be on the upward slope of the learning curve – you want to be on the plateau, where all the lessons have been learnt. Standards are on the up, thanks to a joint effort between pharma companies and their shipping partners, but it goes back to the regulators, who have looked hard at the supply chain. Overall, I would say we are in good shape."