In the past few years, specifically through the COVID-19 pandemic, supply-chain vulnerabilities have become the topic of everyday conversation across all industries — not just among manufacturing CEOs but also everyone from consumers who had to wait months for a new washing machine to healthcare providers unable to keep certain drugs in stock. The pandemic and its global economic disruption made us all more aware of the magic of resilient logistics — and the sometimes stark consequences when they fail.
Arguably, no industry is more dependent on an effective supply chain than regenerative medicine. According to the Alliance for Regenerative Medicine, there are currently almost 1,000 unique products in the pipeline, about 15% of which are in Phase III clinical trials; this is expected to triple in the next 3 years. To keep up with the demand, we need to shorten the timeline between discovery and clinical implementation, which is no easy feat. The speed at which these therapies are developing and the corresponding cycle time for manufacture raises a host of supply chain struggles, beginning with the need to acquire stable and high-quality raw materials. Companies also face labor challenges and the need for temperature-controlled distribution to ensure that final products are delivered in a safe and efficacious condition. But despite the tremendous potential and innovation inherent in these therapies, they largely still rely on cryopreservation techniques that are decades old.
Blood and other biological materials can survive freezing, but they suffer damage from the presence of ice crystals. A cryoprotectant called DMSO often is used to regulate unavoidable ice formation, but it is highly toxic. This not only exposes patients to potentially unpleasant side effects but also can cause irreversible cell damage. Cryopreserved products, especially with DMSO usage, impose multiple risks that require a tightly controlled supply chain that leaves almost no room for error, all the way from manufacture to use in the clinic.
Time constraints and other challenges of transport and storage limit our ability to stock “off-the-shelf” therapies. Prominent examples include complex engineered tissues and CAR-T cell therapies, which take weeks to manufacture and are designed to be highly patient-specific. Another example is the COVID-19 vaccines, most of which required long-term storage below 0°C, cumbersome cold-chain for distribution, and a short shelf life upon thaw (between 2°C and 8°C), making it nearly impossible to deliver them to resource-poor countries.
Hand in hand with de-convoluting an already complex manufacturing and distribution system, if CGT therapies can be safely stored for longer time periods for use at “point-of-need” and shipped with less damage, this can drive the overall cost down and make them a realistic option for so many more patients.
Organ transplantation can also benefit from more-resilient logistics. While the chronic lack of available donor organs once was considered the main bottleneck, it is the challenges associated with their transport that most urgently require addressing. Even today, no matter how many people offer their organs for donation, most of those organs — 80%! — are wasted because they expired or were damaged in transit before they got to where they were needed.
The current organ transport process relies on non-profit organizations to coordinate delivery and pickup in real-time, which often includes collaborations between multiple parties and a lack of reliable means to track availability, enable patient matching, ensure allocation, and track delivery status. Somehow, in the half-century since we began transplanting organs, it is only in the past five years that we are seeing technological advances in organ preservation and transport.
Yet still, organs are left with a narrow time window: 12 to 24 hours to transport a donor kidney and four hours for a heart. Dramatically extending the time window and improving the viable organ placement rate, by developing innovations around the current organ distribution system, will save many of those organs and allow many more people, regardless of where they live, to receive that phone call telling them that a lifesaving organ is available.
In my past work developing tissue-engineered products for regenerative medicine, my focus was primarily on the therapeutic effect for the patient — I gave limited thought to the impact of design on the manufacturing process, pain points in the supply chain, or the logistics of putting a complex tissue-engineered product to use in an actual clinic.
Joining X-Therma helped me realize the bottlenecks that are caused by the challenges of preservation and transport.
I’m confident that my colleagues in this exciting field will continue to discover and create truly disruptive therapies and technologies as fast as disease and diagnostics continue to evolve. I’m equally confident that finally addressing how we preserve, transport, and store these “miracle doses” –– as we are at X-Therma –– will dramatically improve the supply chain and truly open up the potential of regenerative medicine.