Go to waste

No one seeks out inefficiency, but it often creeps in unnoticed when eyes are focused on more immediate concerns. Since the start of the Covid-19 pandemic, however, the disruption to supply chains – and the consequent risk of trials failing – put waste and cost firmly at the top of the agenda.

On the one hand, a drop in demand caused by the suspension of some trials – and partly caused by the hospitals and clinical sites being redeployed to handle the pandemic – meant that even the best-prepared sponsors risked seeing piles of investigational medicinal products (IMPs) go to waste. On the other hand, a desire to push forward with trials in unprecedented circumstances forced many to adopt a more agile approach to the delivery of IMPs. Either way, cost, risk and waste became key concerns.

“Some sites closed completely, others partially and many patients were afraid to go to hospital to get treated,” says Steven Jacobs, chairman of the board at Global BioPharm Solutions and a board member of the Global Clinical Supplies Group (GCSG). “With air travel shut down, getting supplies to sites, which is usually very easy, became very hard. The cargo holds of commercial flights were jam-packed with clinical supplies.”

Usually, around 70% of clinical supplies are flown on commercial airlines rather than being transported by logistics companies. With flights reduced to – at most – 25% of normal schedules, the clinical trials supply chain was, in the early days of the pandemic, brought to a virtual standstill. Some sponsors chartered aircraft at 50 or 100 times the cost of a standard, temperature-controlled clinical supply shipment, but that could only ever be a short-term stopgap. Wanting trials to continue, where possible, the industry faced an immediate challenge – how to get IMPs to patients without contact and without the usual delivery mechanisms – and better communication and collaboration became the only way to identify and mitigate risks in a rapidly evolving situation.

“One of the biggest challenges was that every country was impacted by Covid-19 in a different way and at different times,” remarks Aaron Steinbrecher, clinical supply project manager at AbbVie. “With country borders closing unpredictably, we had to solve how we were going to continue making our shipments. To navigate these challenges during the pandemic, we stayed in constant communication with our site monitoring and affiliate groups, held more frequent team meetings and adjusted shipment timelines on a day-by-day basis.”

Direct action

For some sponsors, the existing mechanisms were sufficient to ensure that supplies flowed in the early days. Ultimately, however, collaboration with logistics partners would prove crucial to their ability to adapt and overcome the challenges of a world in lockdown.

“We use third-party depots (TPDs) to supply sites in certain countries,” explains Steinbrecher. “TPDs ensure that IMP is already in the country and can be released when sites require resupplies efficiently. During the pandemic, countries where we used TPDs enabled AbbVie to easily ship released IMP to sites when needed, avoiding the shipping and customs roadblocks that intensified during the pandemic.”

For some, the direct-to-patient model of IMP delivery would become increasingly important. Normally the preserve of mid-sized pharmaceutical companies, this is a model being adopted – or at least examined – by larger companies. While a patient might visit a clinical site for the first consultation, thereafter IMPs are delivered direct to them by courier.

“Decentralised trial regulations are in place here in the US and in Europe, so we were already seeing a switch to telemedicine, videoconferencing and smartphone apps to replace site visits,” explains Jacobs. “With the pandemic, we had to switch to that overnight, so the direct-to-patient model is growing exponentially.”

One advantage is that this model is less disruptive to the lives of patients who may live a long way from a clinical site. Ultimately, this may help retention and reduce costs. On average, every patient who drops out of a phase-III oncology trial costs $43,000 to replace, according to GCSG.

“Direct-to-patient supply models improve trial enrolment and ease the burden on patients to travel to trial sites for drug dispensation,” adds Steinbrecher. “In addition, it reduces the need for site personnel to receive and dispense drugs. While it is more convenient for the patient when the trial protocol allows, it is a more complex model to set up from a shipping and interactive response technology (IRT) perspective. However, it can be extremely useful, as we saw during the height of the pandemic, as well as in rural areas where clinical trial access is often limited or when a drug can be self-administered.”

For the model to work, logistics partners had to step up with fast-response teams to meet the growing demand and, according to Jacobs, they did an amazing job of helping trials to continue and reducing the risk of wasted IMPs.

“An incredible number of studies were able to continue,” he remarks. “One large company had to put $6bn of clinical studies on hold while it checked all of the perceived problems with state laws – even though there were none – but mid-sized companies were able to quickly adopt the model.”

Waste not, want not

The experience of the pandemic has cast the broader issue of waste in the supply chain in a new light.

“Expiring material is a challenge the industry faces, as it often has to be returned or destroyed at depots, causing waste in the supply chain,” says Steinbrecher. “By using new technology, such as integrated inventory and packaging management systems, we can better predict subject enrolment across countries, and more accurately package and ship IMP to these depots and sites to reduce waste.”

It is not unheard of for sponsors to have a 100% overage for clinical supplies. That kind of surplus of inventory goes a long way to ensuring patients do not miss out on drugs or face delays, but it is very wasteful. Better controls can cut this waste dramatically.

“There is better analysis of enrolment at clinical sites now, and we can use a pull model,” says Jacobs. “Patients can be randomised and then given their doses a few days later, instead of doing dosing immediately. That way, you can plan the delivery of drugs to the necessary sites.”

“Clinical trials have been using the push model for 50 years – like sending lots of produce to a supermarket and keeping it in a giant storage area hoping that someone will buy it,” he adds. “Drugs used to be relatively cheap, so that worked, but today’s biologicals, monoclonal antibodies and comparators have increased the cost massively. Those could cost millions of dollars over the course of a clinical trial, so you cannot afford waste.”

Brought to the top of the agenda by the pandemic, these issues were already a problem because of long-term concerns about sustainability in the supply chain. Worry over climate change and carbon emissions are already driving the industry to be greener and more efficient, but the past year has focused minds on how to achieve those goals through adaptability, redundancy and, inevitably, new technology.

“Improving sustainability in the clinical trials supply chain is not enough – we need to improve sustainability across all supply chains to reduce our impact on the environment,” believes Steinbrecher. “With the development of and investment in new technology, this is increasingly more achievable. At AbbVie, we are continuously monitoring and assessing risk, and identifying opportunities for improvement, innovation and efficiencies in supply chains.”

Action not words

Identifying opportunities for improvement is step one. Step two consists of practical measures to deliver tangible results. “AbbVie is committed to promoting a sustainable supply chain,” says Steinbrecher. “We are also committed to putting controls and programmes in place to reduce risk, minimise waste generation and use waste disposal alternatives, such as beneficial use and recycling. One way we do this is by using reusable shippers when appropriate for the shipment type, shipment location, and drug product. We also use returnable temperature-monitoring devices when applicable.”

For Jacobs, it is all about data. AI, machine learning and, ultimately, deep learning – in which systems create their own algorithms – have great potential, but they require a lot of good data, which is not yet available.

“People don’t like to share how they messed up,” says Jacobs. “The lack of data means it is hard to train an AI to optimise the clinical supply chain. We are moving in the right direction, but there is a long way to go to collect good data and feed the system.”

The response to the pandemic has, in many ways, paved the way to a more cost-efficient, less wasteful and more sustainable supply chain. Nevertheless, the industry must be careful not to backslide.

“In the US, the FDA is happy with how the industry pivoted quickly to a direct-to-patient model,” notes Jacobs. “It is important that we don’t go back to the way we did things pre-pandemic. Decentralised trials, direct-to-patient delivery and telemedicine must all stay in place. In terms of waste reduction and efficiency gains in the supply chain, we have made leaps and bounds in the last decade, but we need to keep improving.”