Technology is transforming clinical trials, especially when it comes to packaging. The latest developments allow clinicians to fit huge amounts of information on their labels, even letting participants watch video updates and change the language of instructions. But with strict data protection laws, digitalising clinical trials is not easy. Andrea Valentino talks to David Dronneau, head of technology, innovation, process and solution at Sanofi, about these challenges, and how future trials could be cheaper for companies and safer for patients.
Until the Industrial Revolution, medical packaging was a rustic affair. Printed from woodcuts on homemade paper, then painstakingly glued on to the packaging by a doctor, even reading the label was sometimes a struggle. But with the invention of the paper machine, around 1800, the process became far more elegant. Apothecaries battled to make their pills and potions stand out, flanking labels with delicate borders, floral motifs and Greek muses.
If today’s labels are now less decorative than their 19th-century forebears, it is a change that can be explained in a single word: regulation. On both sides of the Atlantic, regulators now expect medical manufacturers to fit acres of information on to their labels. FDA wants US pharmaceutical companies to detail everything from the active ingredients in a given drug to dosage instructions and warnings on potential side effects.
The European Medicines Agency (EMA) is just as rigorous, recently publishing new labelling guidelines across every EU language.
Label laws
With all these demands, and capsule cases smaller than ever, there is simply not enough space for the stylish flourishes that patients could once expect. But this frugal approach causes its own problems, particularly when it comes to clinical trials. With the rise of adaptive trials, traditional label-makers are struggling to cope. No wonder the pharmaceutical industry is hunting for solutions.
One of the most exciting involves using so-called ‘smart labels’ to add information to microchips. These developments could transform clinical trials, making the process more efficient and keeping patients safer.
David Dronneau has been involved in clinical trials for more than 25 years. But though his job title has evolved – he long ago swapped his lab coat for a business suit, and is now head of process and solutions at Sanofi – the Frenchman is clearly as passionate for his work as he was in the 1990s. “What is really important is to use IT and technology to help the patient,” he says. “We try to enable the patient to be much more compliant with treatment. Every time we try a new innovation, we look into how it feeds into these issues.”
There is plenty to keep him busy. Vast changes in the way clinical trials are conducted have put immense pressure on traditional ways of labelling drugs and medical devices. On a basic level, clinical trials are getting bigger.
According to a recent study by Grand View Research, the global trials market is due to reach an estimated $65.2 billion by 2025, a 5.7% increase from 2016. At the same time, tests are becoming more international. Just 15 years ago, Asia hosted hardly any clinical trials. That figure has now leapt to over 40,000, a rise supplemented by steady growth in Europe and North America.
But if the cosmopolitan nature of modern-day trials is a boon for pharmaceutical companies, yielding stronger results, it puts pressure on label manufacturers. “If you are working in ten countries – across Europe, for example – you have to develop ten different labels, each in a different language,” Dronneau says. Combined with all that EU and FDA regulation, this becomes incredibly timeconsuming. “It is a very heavy process.”
A broader shift involves study protocol changes, whereby researchers tweak conditions mid-trial. In practice, this covers everything from adjusting drug expiry dates to changing storage instructions. Though this dynamic approach helps researchers – saving time between trials and offering more reliable results – it can cause headaches for label manufacturers.
After all, once a paper label is designed and printed, there is no way to change it. A shift in trial focus dooms outdated labels to irrelevance, a problem recently pointed out by the International Society for Pharmaceutical Engineering (ISPE). According to an ISPE survey, a full 95% of paper labels end up in the bin, discarded before they could ever be used.
If all of this is frustrating and costly for pharmaceutical companies, the proliferation of new technologies can also make paper labels unsuitable for patients.
“With the new therapies that we are putting in place, such as auto-injector syringes, labels are becoming smaller and smaller,” Dronneau says. “It is really complicated to apply the labelling on such packaging. Ultimately, we are giving the patient something useless because the writing is too small for them to read.”
Faced with a surge of useless paper labels, medical companies are not sitting still. Sanofi is investing heavily in smart labels, an area of research that Dronneau considers a “top priority” for the medical industry as a whole. Several other pharmaceutical companies, including Faubel and Janssen, have developed their own ‘smart labelling’ systems.
As Dronneau stresses, this all makes clear financial sense. Using a more agile system lets Sanofi and its competitors “really reduce the cost” of clinical trials.
But for all the fuss surrounding the technology, smart labels are remarkably simple: they are just QR codes, and viewable via any smartphone. What makes them really shine is their data capacity. Rather than stuffing instructions on to illegible labels, clinicians can add huge amounts of data remotely. Even better, researchers are able to change labels on the fly, removing the need to replace them every time there is a change of plan.
Keen to show how fundamentally smart labels have transformed his work, Dronneau compares the situation now with how things used to be. “When we used paper labels, it was really complex and difficult,” he remembers. “If we had 1,000 investigational products [IPs], we had to change them all manually.” But the arrival of electronic systems allowed researchers to: “display the new information immediately and save a lot of time. This new system allows us to push updates really easily.”
If smart labels enhanced clinical trials for researchers, they would surely be worth adopting. As it is, the technology can improve life for patients, too. Instead of squinting at confusing paper labels, they can scan digitalised copies onto their phones, zoom in on instructions and change the font to make text easier to read. Search functionality helps simplify things, as well.
Apart from making the trial process less stressful, Dronneau highlights the safety advantages of this approach. “For example, if we need to push the expiry date of the drug, we can do that really easily and the patient will be alerted swiftly,” he says. “This is really important from a safety point of view, and something that was not really possible with paper.”
Sophisticated labels can leap over the linguistic barriers of their predecessors, too. By way of explanation, Dronneau puts himself in the shoes of the average clinical trial patient. “My smartphone is in French,” he says, “so my label would automatically be displayed in French. [But imagine] I have a smartphone in French, but I am Spanish. We can change the language. I think this is really something to bring the patient into the system we are putting in place.”
These advances dovetail back into making trials more efficient, not least by encouraging patients to actually take their medication. This is a serious problem: apart from compromising the statistical validity of a study, non-compliance haemorrhages cash.
According to Tata Consultancy Services, just 60% of US patients properly follow the trial schedule, a difficulty that costs pharmaceutical companies between $600,000 and $8 million in lost revenue every day. But Dronneau is confident that digital labelling could address this, especially via multimedia instructions, explaining that adding video to smart labels would help patients be “much more compliant with the treatment”.
IoT advances
Smart labels are perhaps the most direct way for technology to improve clinical trials, but they hardly stand alone. Over the past few years, the internet of things (IoT) has affected all aspects of the trial process, from patient enrolment to caregiver feedback.
In his own work, Dronneau is especially excited about how IoT technology could help the trial cold chain. This is particularly important as pharmaceutical companies move towards biologics, which are much more temperature-sensitive than their chemical-based cousins. By equipping capsules with special chips, Dronneau and his colleagues could “monitor their temperature and send information about the shipment [to doctors], ensuring [that] the safety of the patient is preserved”.
Of course, these high-tech innovations cannot reach patients without regulatory approval. Just as FDA and EMA expect companies to keep detailed instructions on their drug labels, so too are they tough on any researchers trying to digitalise their clinical trials. For example, US regulators instruct companies to define “as part of the comprehensive cybersecurity risk management, the safety and essential performance of their device” and “the resulting severity of patient harm if compromised”.
This caution is easy to understand. With patient confidentiality vital to medical life and data breaches frustratingly common, the industry needs to be careful. The arrival of strict new data-protection laws, notably GDPR, hardly help. Dronneau is clearly aware of these pressures, noting that poor security can put off recruits. “We have to respect the privacy of the patient,” he says. “Otherwise they might say, ‘We won’t play your game, because the data will not be used [legally].’ So protections absolutely have to be put in place.”
Despite these difficulties, Dronneau remains sanguine, explaining that Sanofi is collaborating with other pharmaceutical companies to reassure regulators and patients. “We are working in an association where all can work together to define what they would like to put in place.” Not that researchers necessarily have a choice, Dronneau warns. “We need to be willing to take risks. The time is coming where we will need to embrace new technology.” Dawdle and manufacturers risk alienating “a new generation” of younger patients unaccustomed to outmoded practices.
There is every reason to think that Dronneau and his colleagues could manage this transition. With the price of smart chips hovering around the $5 mark, the technology is cheap enough to be used liberally. Just as well: medical labels of the future promise much, even if their decoration leaves something to be desired.