The heat is… off31 January 2020
Temperature-controlled products present a logistical challenge. Their safe transportation and storage are essential to their efficacy. Ensuring effective infrastructure and maximising the use of digital tools are two key strategies to help optimise the supply chain. Didier Basseras, vice-president of clinical supplies for clinical supply chain at Sanofi-Aventis R&D, speaks to Bradford Keen about best practices to keep drugs safe.
In the devastating heat of a summer in Phoenix, Arizona, a postal service worker managed to cook a steak to medium-rare on the dashboard of his delivery vehicle. To quantify that: the internal temperature of the meat was around 60°C.
Perhaps most worrying is that these delivery vehicles don’t have air conditioning. Of course, the safety of postal employees is an important consideration, but, as Vice reported, these are the same trucks that transport birth control pills. Common formulations of contraceptive medication should be stored at 20–25°C, with an excursion of up to 30°C deemed acceptable. Steak-cooking temperatures put those pills at risk.
Faulty contraceptives can have serious consequences for those using them – and indeed, that certain medications need to be temperaturecontrolled is obvious. Yet the above story highlights how quickly poor supply chain logistics can affect the integrity of medication. Granted, large pharma companies tend to have more robust storage and transportation infrastructure than a postal service company, but the complexity of new medicines continues to challenge supply chain logistics teams to adapt processes and practices to protect the important, expensive and potentially life-saving cargo.
Contemporary medicines have shifted from small molecules to biologics, and this has had a significant impact on the clinical supply chain, as well as temperature management. This is a trend of which Didier Basseras, vice-president of clinical supplies for clinical supply chain at Sanofi-Aventis R&D, is acutely aware. Although Basseras began his career in oncology research, he has spent much of the recent past on quality and production management.
“We went quickly from 20% to 80% of drugs requiring cold-chain storage at Sanofi,” Basseras explains. “At the same time, new temperaturemonitoring regulations for storage and transportation require us to manage the amount of time that drugs are out of the allowed range of temperature – both ambient and cold.”
Flexibility and preparedness
There has also been the development of personalised medicine, for example, which is affecting supply chain considerations. These drugs, too, are sensitive to time and temperature. Another concern is that due to the complexity of these new drugs, and the small batches they are necessarily manufactured in, traditional supply chains struggle to accommodate these unique product requirements, and are often unable to provide flexibility in terms of storage and transportation.
Flexibility and preparedness are two targets at which pharma companies and contract manufacturing organisations are aiming. They want to find fresh ways to meet these new demands so they are adapting their standard operating procedures and infrastructure to ensure best practice.
Basseras explains how Sanofi has invested strategically in France and the US to guarantee that it has sufficient cold-storage capacity to keep the increased number of bio-products safe.
Infrastructure includes building cold packaging rooms to pack and label products at a temperature of 2–8°C, which helps to avoid the total time of refrigeration (TOR) for sensitive products. This is the temperature range demanded by regulations, and all parties need to be able to prove that this temperature has been maintained. Key to this is “adapting cold receipt areas and warehouses to get drugs from refrigerated trucks without breaking the cold chain”, Basseras says. Further developments undertaken by Sanofi include equipping cold-storage facilities with fully automated vertical lift modules so that packing drugs for shipping can be sped up.
“Along with these investments, we revisited our depots and distribution strategy – having preferred partners – limiting inventory buffers when possible and reducing the number of possible occurrences for TOR,” Basseras adds.
Sanofi has established a partnership with an active cold-container supplier. Basseras says that these containers help to secure the transportation of large quantities of medications internationally.
“From a cost standpoint, moving from single-use boxes to reverse logistic boxes, combined with a large network of depots, has helped decrease the total cost of shipments and is an ideal approach for circular economy,” he adds.
Digital temperature management
Yet no matter how robust the supply chain is, the logistics team cannot control what happens at a site level, which is where temperature deviations tend to occur.
“Beyond this step, we enter a pain point for TOR management, whereas qualification of the hospital equipment, maintenance and action plan, in case of breakdown, are still a pain point,” Basseras explains, adding that temperature-controlled products used in patients’ homes also present “difficult-to-monitor deviations”.
However, contemporary medicine also has contemporary technology to keep it safe. Data is a valuable tool for logistics personnel. Basseras says that for the cold chain specifically, the acceptable TOR is calculated using stability data.
“The entire temperature life of our products must be tracked and traced, from the treatment kit’s preparation to the patient,” he adds.
Sensors, and the digital tools to make sense of the readings, are key for temperature-controlled storage and transportation logistics. There is a significant shift under way towards digital temperature management, including containers, templates and kits, Basseras says.
The sensor, which is placed close to the drugs, is “loaded with an algorithm based on stability data, and dynamically captures temperature data, duration and temperature to which the drug has been exposed, along with the chain from storage to transportation,” Basseras explains.
If temperature deviation happens, the system can inform the user whether the “total life usability” of the drug has been compromised. “In such a model, we have a clear understanding that guarantees quality when the drug is dispensed to the patient,” Basseras says.
Despite the shift towards digital processes, much of the work at temperature-controlled storage facilities continues to be performed by manual operators, Basseras says. This results in what he calls “hundreds of pages in inventory-management documentation and batch records”.
This is why a digitalised tracking system that can keep tabs on pallets and trading units entering and exiting refrigerated areas is vital in order to make the process more efficient. New manufacturing execution systems – Basseras names Smart Supplies from Brackett specifically – have incorporated digital tools to simplify TOR management for operators.
Integrating IT tools and data sharing
Indeed, the sooner that digital processes can be implemented into the supply chain the better. Basseras considers it best practice for logistics, saying that digital engagement within cold-chain management would deliver optimal results. Equally, gathering and analysing data from end-to-end in the supply chain is essential.
However, to make this approach truly successful, pharma companies and their logistics partners need to be embedded into what Basseras calls “a seamless cold chain”, which requires greater integration of all stakeholders’ IT tools and data-sharing capabilities.
Basseras stresses that the safety of the patient is important to consider at all times. Keep the end user in mind and be guided to meet their needs, whatever logistics are required. One way to achieve this is to consider sharing the stability data of products across companies; it is a stirring thought, one that should be considered by pharma companies. However, the likelihood of such an approach remains small.
Consider just how competitive an environment investigational drug development is. Big pharma companies are looking to create new drugs and get them to market as quickly as possible, with each trying to demonstrate the superiority of their product. Amid this competition, the patient is sometimes forgotten.
“Even if some gentlemen’s agreement can be discussed and agreed to while sitting on industry forums, it could all be discarded when competition intensifies,” Basseras says.
By putting the patient back at the core of the drug manufacturing, along with the subsequent transportation and storage of medicines, interorganisational collaboration – even between competitors – could be possible. At the very least, sharing stability data could lead to new solutions for patients and ease the pressure on the cold chain.
And easing the cold chain is essential for the proper storage and transportation of drugs. Part of that, in addition to sharing more data and implementing digital processes, is to match the drug stability more accurately with the storage requirements. Currently, the cold chain is burdened by “storage requirements that can sometimes exceed what is really needed”, Basseras says. “We need to anticipate early all of the requirements to secure the full chain.”
Protecting patients requires drugs to be kept safe, and it is pharma companies and their logistics partners that are tasked with this challenge. Working collaboratively, building contemporary and robust infrastructure that can store and transport sensitive products, maximising the use of data, and embracing the shift towards digitalisation are key. Meeting these requirements will help to ensure best practice and safe patients.
Delivering temperature-controlled medications with drones
In the healthcare context, the timely delivery of medications, vaccines and blood is crucial. Drones can potentially overcome the logistics challenges as they are not subjected to traffic delays and, most importantly, they are able to reach regions faster that lack adequate roads. However, for delivery of fragile medications, blood and diagnostic clinical laboratory specimens, drones are practical only if the quality of transported products is not adversely affected. Thus, drones as a novel method for medicine transportation must be tested to determine their impact on the medicine quality.
In the UK, drone delivery has a potential to thrive, as reported in Nesta’s ‘Flying High’ report in July 2018. The Flying High Challenge explored drone use in urban areas, and the technical and economic feasibility of delivering blood samples or medical supplies between hospitals (Guy’s and St Thomas’ in London) was evaluated.
A number of challenges were identified; in particular, the legislation requiring flying drones in the line of sight. Apart from such regulatory and safety issues, drones exhibit some technical limitations with regard to battery life, payload capacity and maximum coverable distance. Furthermore, the misuse of drones to deliver illegal drugs to prisons has led to low public confidence and acceptance of this technology.
Critically, however, no information on the quality of medicines delivered using drones was considered in the report, which highlights a significant knowledge gap. While a few pilot studies have been carried out on drone delivery of medicines to remote areas, there has been little consideration of the impact of the flight conditions on the quality of the drone-delivered medicines.