There are two major problems when it comes to transporting ambient-temperature pharmaceutical products, and they’re intimately linked. The first is that there are too many definitions for ambient temperature and many people disagree about what the phrase actually covers. This leads to the second problem: a global inconsistency during transportation.
“The definition is where we should start in order to move towards harmonisation of the regulatory framework around the world,” says Savvas Koulouridas, general manager at Fagron Hellas, which supplies raw materials for pharmaceutical compounding.
WHO notes that the term ambient temperature is “not widely used, due to significant variation”. More common terms are room temperature or normal storage conditions. Whatever the phrase, the organisation puts the temperature range at 15–25°C, climbing to 30°C, depending on climatic conditions. The storage area should be dry, clean and well ventilated.
“When we talk about ambient-temperature products, I find it very hard to see well-documented deviation protocols that can ensure that a product that sits in 40°C in the middle of the airport at Dubai, for example, is a product that can be properly distributed,” Koulouridas says.
The most important goal of transporting pharmaceuticals is to ensure the integrity of the products. Koulouridas believes that patients should be the focus point for all companies involved in the supply chain network. “We need to check the means of transportation and the storage conditions, along with the key role of every single link in the transportation chain,” he states.
Maintaining this integrity is essential to ensure effectiveness and safety, but this is not an easy job. Transport companies and third-party logistics providers need to be carefully validated, which can be a challenge in itself. However, there are certain deviations that can never be controlled, such as weather or unpredictable drivers.
“I have seen many drivers diverting for any number of reasons to routes where they end up stuck in snow or heat for a few days,” Koulouridas says. “Certain deviations of products may be documented, but who decides if this product is acceptable or not? There is no clear understanding of when a deviation is acceptable.” This calls for more precise information about the effects that certain weather conditions or temperature deviations can have on products. Of course, choosing the right packaging solution is a big part of maintaining control of temperature during transportation.
Active or passive
Passive systems refer to standard water-based refrigerants and insulated containers, and specialised refrigerants or phase-change materials. They are suitable for tighter temperatures, Koulouridas says, and also, depending on the system, have reverse-logistic capabilities, which enable them to be reused all year round.
Active systems rely on temperature-controlled trucks and ocean containers, as well as pallet and parcel-size containers. They ensure goods are constantly handled and shipped at the optimum temperature. “Both systems have their pros and cons,” Koulouridas says. “It depends on the specific needs of the product.”
It is also a matter of the technology behind the temperature control. “I see lots of evolution, and I will not be surprised in the future to see temperature control on single packaging, especially on cold chain shipments – not ambient temperature – even if it refers to the last-mile transportation or one step before that,” adds Koulouridas.
Part of the difficulty of managing the shipment arises along the ‘last mile’ of the supply chain, after pharmaceutical companies have transported their products to the wholesalers. “Interest stops at wholesalers,” he says. “We never check on what’s happening on the last mile. We are not checking how pharmacies and wholesalers are transporting and storing the products in different countries.
“The pharma industry spends millions to ensure the product arrives safely at the wholesaler and that it does something beyond imagination. If the product arrives in a pharmacy that does not have the proper storage facilities, the patient receives a potentially unsafe product and everything has gone wrong in the final two steps.”
The problem lies in poorly validated transport companies or thirdparty logistics providers used as intermediates that do not follow basic principles of good distribution practice (GDP). Failure to enforce the positioning of data loggers on the shipment is another issue related to non-compliance. For example, these devices cannot go in the centre of the shipment because the temperature in the centre remains more consistent than at the extremities.
“As long there are no proper guidelines that say ‘this is how you should pack this category or product; this is where you should put the data logger; and make sure this is followed during the whole transport chain’, then it is really hard to say we can have a harmonised system, or make sure that the product is 100% safe for the patient,” explains Koulouridas.
While ambient-temperature products do not require as much sensitivity as products in the cold chain, there still needs to be more understanding and communication from the pharma industry about what are acceptable and unacceptable deviations. Koulouridas says once this is done, the whole transport chain can adapt to the recommendation. “From what I have seen, there is different implementation of GDP around the globe, including temperature deviations and the kind of data we have available on all products in terms of these deviations,” he explains.
Finding a global standard
Koulouridas spoke at the Temperature Maintenance of Pharmaceuticals in Distribution conference in Barcelona earlier this year. He talked about the need for regulatory bodies and pharma companies to collaborate and increase flexibility within GDP requirements.
He says a common question asked at the event was not only how maximum requirements can be set around the globe, but how to ensure they will be properly implemented. Despite the monumental task of getting different countries and regulatory bodies to conform to a worldwide standard, Koulouridas is confident the challenge can be met. However, the approach requires flexibility.
The tendency is to push for harsh implementation of GDP or WHO guidelines covering the transportation of ambienttemperature products. Koulouridas recently heard about FDA in the US and the European Medical Association (EMA) trying to decide how to perform audits on companies to determine whether or not they are adhering to GDP. Part of this involves anticipating how pharma companies, producers and wholesalers will adapt to these requirements. This method requires a strict qualitymanagement system. “It can be done, but the question is do we need that?” Koulouridas asks. “It’s like using a Ferrari to go to the grocery store that is just a minute down the street.”
When it comes to low-cost products in particular, Koulouridas says “a very strict approach” to temperature control may be unnecessary and expensive. “We see around the world, including Europe, that health budgets are being cut,” he states. “Are we ready to face the consequences of bigger prices on medication?”
The issue of non-compliance between countries and regional regulatory bodies remains another challenge. “You have irregularities and unfair competition in the market that comes from the regulatory bodies that do not issue GDP certificates,” Koulouridas says. “I see that with many transportation companies – they say, ‘we cannot guarantee that we have GDP certificates by our authorities because they say they cannot provide it’. It becomes a challenge.”
He favours a risk-based approach instead, the value of which is seen in terms of keeping down the cost of medicines. This, in turn, renders them more readily available to patients. The riskbased approach requires returning to the laboratory to determine the safe range of temperature deviation for every product. This information can only be delivered by the producers, so it is not without its own set of challenges.
Cost-effective solutions
One issue that plays a significant role in determining the best supply chain solution for transportating all medicine, including ambienttemperature products, is cost-effectiveness. This does not necessarily mean finding the most favourable price. “We need to consider further costs, such as products that might have any deviation, recalls and other unforeseen issues we need to take into account,” states Koulouridas.
Of course, the most important consideration is to evaluate the transport companies. He says there are a lot of mistakes when the pharma industry chooses the wrong third-party logistics provider for transporting products. The best way to be cost-effective, he says, is to have proper checks and validation. According to Koulouridas, cost-effectiveness can also be met through the riskbased approach. Studying the product-specific requirements – and adapting the transport technology to these needs – will help guard the integrity of medical products.
Koulouridas admits that this approach may sound like “watering the desert”, but he maintains this is the best path to pursue. “We need to fix the issues we have in different countries that are playing a significant role in the production of raw materials across the globe,” he explains.
“From a technology point of view, a risk-based approach and adoption might be a good answer for the future, but we need to look in our own closet to see if producers across the globe are meeting the basic requirements of GDP, and how they’re implemented in different countries.”
The validation of transport companies will play a big role in ensuring the safety of medical products. However, there are other big issues that need resolution, such as choosing reliable transport routes and effective storage areas. “There is a lot of room for improvement,” Koulouridas says.
Finding agreed terms to use when discussing how best to transport ambient-temperature shipments is the first step to ensuring product integrity. Obviously, temperature fluctuates due to specific climates and storage areas at different locations. This means that greater attention must be given to harmonising the international differences when it comes to GDP. There is a tough road ahead, but industry players must navigate it together to ensure the integrity of all medical products along the supply chain.
