Is A Fully Functioning Cell Therapy Global Logistics Network Achievable?
By Erin Harris, Editor-In-Chief, Cell & Gene
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Cell therapy products require either just-in-time delivery to patients or cryogenic storage temperatures to preserve the cells in a metabolically inactive state. Currently, there is a lack of existing cold chain infrastructure to meet these requirements, particularly from a commercial supply chain perspective. Is a fully functioning global cold chain logistics network for cell and gene therapies even achievable? The bad news: probably not — at least not in the foreseeable future. The good news: more and more companies are continuing to invest in accelerating cold chain capabilities domestically and across the world to reach even the most remote areas. Expanding a GMP network, including a cold chain and adequate storage, is critical for cell and gene developers to reach previously unreached areas.
Achieving Global Expansion — from Storage to Manufacturing
Storage challenges exist for any logistics network, as Dr. John Harrington, EVP and CSO at Athersys, explains in his article for Cell & Gene. Dr. Harrington explains that storage and distribution of cell therapy products pose challenges because cells lose both their viability and potency over a short period of time under inadequate conditions. Whereas antibodies and small molecule drugs are relatively stable, often at ambient temperature, cell therapy products must be maintained in the frozen state at ultra-low temperatures below the glass transition temperature, generally below minus 120 degrees Celsius. He also writes that to accomplish this, validated shipping containers capable of maintaining these low temperatures for up to one week are utilized to facilitate the transfer of product from the manufacturing site to clinical sites around the world. Of course, ultra-low temperature freezers are required prior to shipment and at the clinical site following shipment for storage prior to use and monitoring of temperature is necessary to ensure that temperature excursions have not occurred.
Consider mRNA, CAR-T, and viral vectors for example. Marken, in its clinical trial logistics operation with UPS Healthcare, has expanded its global network to support increased demand for its clinical drug supply chain services, particularly for cell and gene clinical trials and — depending on location around the globe — GDP or GMP storage. These investments should matter to cell and gene therapy developers, as increased innovation enabled by mRNA, CAR-T, and viral vectors will only continue. The cell and gene sector is experiencing real-time expansion in the cold-chain network, which is helping to deliver vaccines, such as mRNA vaccines as well as cell and gene therapies to remote areas around the world, such as Ghana and Kenya.
Indeed, the global expansion in GMP facilities provides value for the entire cell and gene therapy sector. “When you think about allogenic treatments for patients for example, especially those who need multiple dosages over a given time, we need to overcome import challenges and have GMP facilities in countries where we know the logistics might be a deal breaker to get the treatment in time to the patients,” says Ariette van Strien, president of Marken. “The overall benefit is making cell and gene therapy more patient-centric. The big question remains, what are we doing from a logistic or supply chain perspective? Does it make a difference to the patient? Ultimately, we can get closer to the patient and make sure we overcame all the hurdles, which means building GMP facilities where it makes strategic sense.”
To van Strien’s point, a functional cell and gene therapy global logistics network is achievable in that technology, equipment, and shipping have improved tremendously in a short time. In the stem cell donation world, for example, once the cells have been collected the clock starts ticking on the 72-hour window to get the products to the patient for infusion. The logistics, scheduling, and hands–on monitoring requirements to cross borders and include long–haul flights result in high-stress circumstances that demand a functional global logistics network.
Cryopreservation and Innovation in GMP Manufacturing
Increased innovation in cell and gene therapy manufacturing is important for the progression of a functional logistics network. “Innovation in cell and gene therapy manufacturing could bring autologous to allogenic, or liquid nitrogen -150C temperatures to room-controlled temperature, which will allow us to use a much more solidified supply chain or logistics network. The more we innovate on the manufacturing side, the more we get to normal temperatures and the easier it will be to get treatments to the market and patients,” explains van Strien.
My colleague, Chief Editor of Bioprocess Online and host of the Business of Biotech podcast Matt Pillar, talked to Celyad Oncology head of cell therapy manufacturing, Thomas Lequertier, about best practices for the cryopreservation of cell therapies while minimizing cell degradation. During the episode, Lequertier explained that maintaining therapeutic integrity through cryopreservation and super-cold supply chains have challenged biologics producers and that maintaining the therapies’ integrity on the journey from the lab to the patient is as detailed as it is complex. “For allogeneic therapies in particular, the challenge is in producing as much as possible,” explains Lequertier. “Identifying equipment that can manage hundreds or even thousands of doses and cryopreserve them is a big challenge for the future.”
Speaking of podcasts, I host Cell & Gene: The Podcast, and recently, I talked to Dr. Murat Kalayoglu, CEO at Cartesian Therapeutics about the cell and gene therapy sector's advancements in RNA cell therapy and the why behind the company’s decision to build its own wholly-owned GMP manufacturing facility. The company's novel approach to RNA-engineered cell therapies for oncology is what drove Cartesian to build its own facility. During the episode, Dr. Kalayoglu details the most challenging aspects of manufacturing at scale, including storage, temperature control, and more.
Finally, as Paul Stroemer and Paolo Siciliano of PA Consulting explain in C>s : A Roadmap To Solving 6 Challenges Over The Next Decades, cell and gene therapies are likely to play a key role in reshaping the way we think about and approach medicine and disease treatment, across most therapeutic areas. However, the path to success for these revolutionary therapies is still paved with technical and commercial hurdles that need to be overcome for cell and gene therapies to achieve their full potential. And a global logistics network is a MAJOR component on the path to success. Instead of thinking about logistics as an insurmountable problem, biotech companies need to make it a critical path of any therapy development and consider involving a logistics partner at Phase 1. If biotechs do not think ahead about logistics, they might choose technologies that will be obsolete in just a handful of years and will lose critical months or perhaps even years while validating new packaging solutions. The earlier biotechs can involve the logistics and supply chain industry, the better prepared the company will be able to bring a therapy to market. And, the more globally functional the network, the faster trials can be launched, because biotechs will already have the different supply chain and logistics lanes mapped out with contingency plans in place.