Pharma’s Cold Calling: CGT Space at a Critical Crossroads

Andrea Zobel, PhD, Senior Director, Personalized, Supply Chain, World Courier, a part of Cencora

Seven years after the FDA’s landmark approval of a gene therapy, clearing the way for leukemia drug Kymriah,¹ the cell and gene therapy (CGT) sector is now entering a new era.

Driven by significant R&D investments and scientific advances, new modalities are now reaching the market and an influx of therapies are on the horizon, including products that target larger patient populations. One of the fastest-growing areas is the development of allogeneic cell therapies, which represent 50% of Phase I cell therapy trials.²

Allogeneic cell therapies are collected from donors, cultured, and expanded, and then used to treat many patients. More than 470 allogeneic cell therapies are in different stages of preclinical and clinical development,³ and the global market is projected to increase significantly in the coming years, growing at a compounded annual growth rate of 14% from 2023 to 2035.³

Allogeneic cell therapies—often referred to as “off-the-shelf”—can be more efficiently manufactured in large batches, easing some of the challenges associated with autologous cell therapies in which a patient’s cells are collected, genetically modified, and then returned to the patient. The approach—and efficiency in which these products can be manufactured at scale—offers the potential to accelerate time-to-treatment and broaden access to innovative therapies globally.

PLANNING—AND PREPARING—FOR THE LOGISTICS CHALLENGE

Most of the cell therapies in clinical development today are of autologous origin. For these treatments, developers and their partners must manage two time- and temperature-critical supply chains: first from the patient to the manufacturer, and then from the manufacturer back to the patient.

Allogeneic approaches introduce their own unique logistics considerations. Unlike autologous approaches, the supply chain doesn’t start with the patient. Instead, the donor cells are collected and then transported to the manufacturer for modification and filling and finishing before being shipped to a good manufacturing practice-compliant storage facility, where products are kept frozen for on-demand delivery. A single batch of engineered cells can potentially treat hundreds of patients.

Like autologous cell therapies, allogeneic products remain viable only within narrow ranges of time and temperature. For example, fresh cells have a shelf-life of between 12 and 96 hours before they begin to degrade.

EXPANDING CRYOGENIC LOGISTICS INFRASTRUCTURE GLOBALLY

One option to extend the shelf-life is to freeze cells using cryogenic storage techniques. Cryogenic transportation is a specialized logistics process designed to safely transport materials that need to be kept at extremely low temperatures, typically below -150°C. Cryogenic logistics enables long-term storage and can preserve the product’s integrity and viability across long-distance shipments.

However, certain markets—including more remote locations—may not have the specialist facilities needed to support cryogenic storage.

As the number of allogeneic therapies in clinical development increase, there is a heightened demand for cryogenic logistics infrastructure globally. In a survey of leaders at companies developing CGTs, nearly 60% of respondents indicated that their need for cryogenic transportation and storage services would grow significantly over a three-year period, ending in 2024.⁴

Robust cryogenic logistics infrastructure—including facilities close to processing facilities and healthcare providers—is critical to support scalability of allogeneic agents and enable access to these products around the world. As an example, World Courier, which delivers more than 12,000 cryogenic shipments around the world annually, has made significant investments in recent years to establish a cryogenic cold chain—integrating transport and storage—spanning every inhabited continent.

An effective logistics operation also requires real-time temperature and location monitoring capabilities and advanced packaging solutions, such as dry shippers. Dry shippers are filled with nitrogen vapor that maintains the internal temperature between -150° and –200°C for extended periods. In order to support the cryogenic supply chain, appropriately trained staff members are responsible for handling dry shippers. Their duties include refurbishing the dewars through cleaning, logging, and inspecting them, as well as ensuring they are properly conditioned, ready for use, and kept in clearly designated areas.

The preparations take time, particularly when a charging center or station is in another country from the clinic or manufacturing site. Continued investment in these facilities globally—and larger shipper solutions—will be critical to support efficient and timely shipments of these products. As an example, even Phase III clinical trial shipments often contain hundreds of vials or bags, requiring 10 to 30 dry shippers. For an effective commercial supply chain, large movements of therapies across the globe must be anticipated.

LOOKING AHEAD

Coming off a record-breaking number of FDA approvals in 2023, the CGT market is poised to experience significant growth in the coming years.

As the sector enters a new era—and the number of allogeneic cell therapies in late-stage clinical development increases—it’s imperative we have the infrastructure needed to support the unique time and temperature requirements of these products. To realize the full potential of these therapies, healthcare stakeholders across the supply chain need to continue to prioritize investments in technology solutions, such as monitoring capabilities,
and infrastructure to enable the secure and reliable delivery of these products.

Through early planning and collaboration, CGT developers and their partners can overcome the unique logistical challenges across the clinical and commercialization journey and ensure products can reach the patients who need them.

Andrea Zobel, PhD, is Senior Director, Personalized, Supply Chain, World Courier, a part of Cencora

References

1. FDA Approval Brings First Gene Therapy to the United States. FDA press release. August 30, 2017. https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states

2. The Sector Snapshot: August 2024. Alliance for Regenerative Medicine. August 2024. https://alliancerm.org/sector-snapshot-august-2024/

3. Global Allogeneic Cell Therapy Market Trends and Forecasts, 2023-2035, Featuring 378 Companies and Unveiling Key Regional Opportunities. Business Wire. August 4, 2023. https://www.businesswire.com/news/home/20230804080604/en/Global-Allogeneic-Cell-Therapy-Market-Trends-and-Forecasts-2023-2035-Featuring-378-Companies-and-Unveiling-Key-Regional-Opportunities---ResearchAndMarkets.com

4. Cold Hard Facts About Cryogenic Cell and Gene Therapy Logistics. Cencora/World Courier survey. https://marketing.worldcourier.com/l/168232/2022-10-10/5hyhgn/168232/17102130649pz2pl8N/Cencora___CGT_Whitepaper___210x297___RGB___V26__2_.pdfBody_noindent_justified_dropcap