Amaury Jeandrain

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Although the need for sustainable practices has arisen in many areas, the clinical trial supply industry has always had to make a choice between patients’ health and an efficient supply chain, with the former always being the priority.

Indeed, the primary focus of clinical supply chain managers has always been, and will always be, to ensure patient safety and treatment continuity above all else. Any delay or disruption in the clinical supply chain can lead to serious consequences for its patients. It is, therefore, understandable that clinical supply chain managers prefer to take buffers and significant safety stocks into consideration. It is also easy to see how these precautions automatically generate more waste in the supply chain. These practices, in our experience, are inherent to every clinical trial and are deeply ingrained in the industry as being standard.

But, as technology is evolving, we are now able to connect the best of both worlds, bringing together sustainable practices into the clinical supply chain while ensuring zero-risk for the patients.

The importance of sustainability in clinical trials

We could summarize into three sustainability pillars the main areas where clinical supply chain is looking to improve its performance:

It is crucial to reduce the CO2 emissions and carbon footprint caused by heavy manufacturing, packaging, transportation, and even the destruction of drugs that end up being wasted in a trial. Today, when we analyze the end-to-end clinical supply chain, on average 70% of the drugs produced will be thrown away and destroyed, without ever seeing the hands of a patient.

Regarding resource management, we are well aware that the earth’s resources are finite. In the past years, we have faced a shortage of raw materials that are critical to the manufacturing of medication or their vials, along with an increase in their pricing. We have also faced a shortage of manufacturers in the biologics area in the past four years. Delays are therefore frequent, and budgets may become scarce as well. Pharma companies may very well be in a situation where they have to postpone developing new life-saving treatments due to a lack of resources. High waste levels in the industry are therefore starting to become a focus.

On the side of ethics, clinical supply chain will of course continue to keep patient safety as a priority. But clinical supply can also impact patients outside of clinical trials. The FDA reported an average of 100 drug shortages every year since 2007

, with 2022 being a record year (295 shortages

), and 2023 expected to be even worse according to experts. Some of these shortages are life-saving drugs, such as chemotherapies. This scarcity of resources has forced hospitals to ration out drugs by reducing doses to extend the supply and prioritize patients who would benefit the most from treatment.

 Most of these drugs are also used in clinical trials. Considering this, and the fact that 70% of drug in clinical trials is wasted

, the industry is faced with an ethical dilemma.

In its way to uphold patient safety, the clinical trial industry must however consider the impact of its actions on the overall sustainability, which we can no longer set aside. As we’ve established, this can lead to high levels of drug waste and shortages of existing treatments and resources that could have benefited patients instead, through immediate drug availability or long-term research. All while generating high levels of emissions. Well aware of the urgency, big players in the pharmaceutical industry, such as AstraZeneca

 amongst others, have now committed to a net-zero emissions goal within the next decade. And digital twins can definitely play a part.

Digital twins have become somewhat of a buzzword in supply chain, regardless of the industry. Its scope of application is quite wide, but for clinical trials, it means that you can virtually replicate the entire supply chain of a clinical trial by accurately mimicking its design (e.g. protocol, manufacturing and distribution network, IRT). This means that you can clearly identify, years in advance, what will happen in the future of the trial (risks, waste, CO2, shipments, etc…) with high accuracy. It also means you can tweak the digital twin, modify decisions, and simulate unexpected events. You will then identify potential issues and inefficiencies before they occur in the real world. This can ultimately improve the supply-friendliness of the clinical trial, ensure patient-centricity as well as guarantee a better utilization of resources.

Case study: a respiratory drug trial during COVID

During the pandemic, we had the opportunity to collaborate on an interesting case study using a respiratory drug to treat the symptoms of COVID. The trial design was already challenging in itself and included 500 patients to be enrolled in 12 different countries over a two-month period.

To test the efficacy of their drug, the sponsor also had to purchase a comparator, a drug commonly used on the market to treat respiratory diseases. But as COVID was ongoing, the comparator was in shortage. In the end, they could get their hands on only 2,300 units, while 4,200 units were originally required (according to our digital twin) to make the trial feasible without risk for patients, in its current design. Simply put, the challenge was primarily to make the trial feasible altogether.

Through a digital twin approach, N-SIDE could replicate every aspect of the initial trial setup and successfully run multiple alternative trial designs and supply chain strategies using simulations and optimization algorithms. For each alternative twin, the sponsor had access to key KPIs, such as the risk of shortages in the trial, waste, costs, number of shipments, etc…

After analyzing the suggested strategies, multiple options existed to make the trial feasible. The sponsor could confidently choose the one that fitted their operational constraints the best, while ensuring a fast-enough recruitment speed. To get to this optimal scenario, changes were made to multiple areas of the trial design. Three of the most impactful were:

The first area of improvement was to implement two changes to the protocol design, allowing to save a considerable number of drugs:

Patients were supposed to have one dispensing visit initially. It was recommended to split it into two visits, and dispense one kit per week instead of two upon randomization

Reduce the visit window to ensure site resupply prior to visit two.

A second area was to increase the supply chain’s efficiency by:

Negotiating with the CMO to reduce the site shipping lead times to two to four days

Since the country list was not final, there was flexibility to recommend including or excluding certain regions and local depots that generated high waste for low recruitment projections

Due to fast recruitment, it was expected up to 10 patients would be screened on the same week at a single site. The last implemented recommendation was to cap the recruitment per site to four patients per week, in order to reduce site inventories and keep drug where it was actually needed.

Overall, in this clinical trial, a digital twin tackled all three pillars of sustainability:

Emissions: shipments were reduced by 30%, and packaging and destruction by 35%.

Resource management: only 1,980 units of comparator were needed instead of 4,200. The next manufacturing batch of the investigational drug was also canceled. These budgets could then be used elsewhere.

Ethics: the trial was started on time, with potentially a new treatment on the market coming as soon as possible. 320 units of the comparator drug were also re-introduced into the market at a time of drug shortages, making it available for sick patients.

By providing a way to model and understand how to reduce carbon footprint efficiently, and quantifying the impact of any event, digital twins bring confidence into decision-making, and enable more actions to be taken without worrying about risks for patients. And with sustainability being an imperative, we strongly believe that this will accelerate adoption in the upcoming years.



Based on N-SIDE’s experience and audit at their clients.

Drug shortages. US Food And Drug Administration. July 2023. 

https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages

Christensen J. New drug shortages in the US increased nearly 30% in 2022, Senate report finds. CNN. March 2023. https://edition.cnn.com/. 

https://edition.cnn.com/2023/03/22/health/drug-shortages-senate-report/

Kimball S. FDA considers temporary cancer drug imports from unapproved companies to ease U.S. shortage. CNBC. June, 2023. 

https://www.cnbc.com/2023/06/01/cancer-drug-shortage-fda-mulls-overseas-chemotherapy-imports.html

Based on N-SIDE's own analysis of waste trials that did not use optimization.

AstraZeneca’s ‘Ambition Zero Carbon’ strategy to eliminate emissions by 2025 and be carbon negative across the entire value chain by 2030. January, 2020. 

https://www.astrazeneca.com/media-centre/press-releases/2020/astrazenecas-ambition-zero-carbon-strategy-to-eliminate-emissions-by-2025-and-be-carbon-negative-across-the-entire-value-chain-by-2030-22012020.html#

GSK’s Environment. Our sustainability goals and target. 

https://www.gsk.com/en-gb/responsibility/environment/

Pfizer announces commitment to accelerate climate action and achieve Net-Zero Standard by 2040. Pfizer. June, 2022. https://www.pfizer.com/news/announcements/pfizer-announces-commitment-accelerate-climate-action-and-achieve-net-zero.

Articles

Digital twins allow the industry to integrate sustainable practices and supply chain efficiency solutions while ensuring patient safety.