The discovery of several genes responsible for mutation in various diseases over the past two decades has propelled growth of the advanced therapy market. Valued at $4.99 billion in 2021, the cell and gene therapy (CGT) market is predicted to grow at a CAGR of 39.62%—reaching $36.92 billion by 2027.¹

And while breakthroughs in advanced therapeutics continue to transform modern medicine and offer new hope to patients, the research and development of products derived from patient cells present specific supply chain challenges for sponsors.

Autologus therapies demand intricate vein-to-vein supply chains. Limited product availability, the fact that patients are typically very unwell—so disruptions in the supply chain could result in significant negative patient impact—and therapy identification are key drivers shaping effective supply chain design.

While allogeneic cell therapy products offer greater flexibility in patient pathways, they also present several recognizable supply chain challenges.

The challenges of allogeneic cell therapy supply chains

Perhaps the most obvious challenge of allogeneic cell therapy supply chains is cold chain handling: minimizing the likelihood and maximizing the detectability of temperature excursions from production line to patient.

To preserve the integrity of allogeneic cell therapies secondary packaging, shipping and storage must maintain cryopreservation temperatures below -135°C. Expedited shipping times are also required, to reduce the risk of temperature excursions in transit. 

Allogeneic cell therapies are Made to Order or Made to Pack, which creates limited product availability. Advanced therapeutics are also high value commodities, with the cost for manufacturing one batch of CGT product typically varying between $500,000 and $1m.² These factors combine to significantly reduce the margin for error compared with traditional pharmaceuticals.

Failure to uphold product integrity for a single patient dose can not only negatively impact that patient but compromise the commercial viability of the study itself.  This warrants precision chain of custody (COC) surveillance throughout the product lifecycle, which can be difficult for many sponsors to establish.

Other limitations that serve to create more complex supply chain operations include unpredictable recruitment. Being patient-specific and primarily used to target rare diseases or last-lines of therapy, CGT – including allogeneic products – serve smaller patient populations, due to low disease prevalence and/or strict eligibility criteria.³ This serves to cloud visibility for forecasting and heightens the risk of product waste and/or the likelihood of shorting sites and losing patients from a trial. The limited stability of allogeneic products and short expiry dates combine with unpredictable recruitment to create a perfect storm where inefficiency and risk can escalate. 

When it comes to packaging and labelling, the short shelf life of products and personalized patient dosing and packaging required, places a demand on sponsors to deliver rapid yet bespoke operations. In turn, the variability of starting materials between lots, typical with allogeneic cell therapies, render standard labelling operations unworkable. Instead, multiple labelling operations are required, increasing the risk of introducing unmanageable cost or inefficiency.

Building safe and effective supply chain strategies

Understanding the complexities of allogeneic products and designing safe and effective supply chain strategies is essential to ensuring the right drug is delivered to the right patient at the right time and within specification.

Key to achieving this ideal standard is delivering a fast turnaround from drug order to dispatch, maintaining visibility throughout a drug’s lifecycle and implementing robust temperature controls. Prioritizing strong communication between key supply chain stakeholders to increase competency in overcoming challenges—from environmental conditions to regulatory and customs requirements—quickly and effectively is also imperative.

There are several strategies sponsors can adopt to expedite timelines. LEAN manufacturing processes, such as Just in Time Manufacturing, deliver value to CGT trial sponsors by helping to overcome the challenges of low yield, high value products and unpredictable recruitment. By delaying packaging operations until the actual demand is known, supply flexibility is maximized, waste is kept to a minimum, and timelines fast-tracked.

The same can be achieved by embracing integrated manufacturing, expert data management, and strategic logistics to optimize operations. Personalized clinical packaging and labelling solutions, which utilize specialist materials designed to cater for the precise needs of CGTs, also have an important role to play in responding to patient demand with both speed and precision.

Maintaining end-to-end supply chain visibility is another vital component; supporting sponsors to effectively track and trace CGT product throughout its lifecycle and demonstrate a robust chain of custody. Alongside use of fully validated processes and expert people, closed loop supply chain technology supports sponsors to effectively coordinate studies in real time. By prioritizing system integration, technology can also be harnessed to link geographical tracking data with temperature monitoring data to provide a bigger picture view.

Creating cryogenic cold chains and expediting the timelines associated with traditional pharma is necessary to uphold product integrity and promote study success. To maintain specific temperature requirements and ensure product viability, products must be stored and handled utilizing ultra-cold ice or liquid nitrogen. This not only demands robust cold chain capability covering production, storage, and distribution but requires sponsors to have access to control tower knowledge covering shipping lanes, country-specific customs clearance times, and regulation governing CGTs to monitor shipments in transit and avoid delays that could jeopardize safety and performance.

There are several tools sponsors can adopt to help uphold temperature control through distribution. These include: reusable, phase change shipper solutions, temperature monitors covering all stages of distribution, centralized temperature management systems, end-to-end logistics insight, a network of reliable couriers and access to global regulatory compliant facilities and depots.

Ultimately, to keep pace with the demand for CGT products, perform well in an increasingly competitive CGT drug development market, and support the CGT breakthroughs of tomorrow, sponsors must prioritize establishing complete end-to-end supply chain visibility. Implementing the right technology, utilizing the right processes, and harnessing the right people is fundamental to achieving this objective. 

References

1. https://www.reportlinker.com/p05827567/Cell-and-Gene-Therapy-Market-Global-Outlook-and-Forecast.html?utm_source=GNW
2. Deloitte. Distribution and supply chain models in the cell and gene therapy landscape. June 2021.
3. Deloitte. Distribution and supply chain models in the cell and gene therapy landscape. June 2021.

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Lyn McNeill is the Just In Time Manufacturing Solutions Manager at Almac Clinical Services in Northern Ireland, responsible for service implementation, stakeholder engagement and development of Almac’s Just In Time service suite. Lyn joined Almac in 2016 as a project manager in Clinical Technologies. In this role, Lyn was responsible for overseeing a wide IRT portfolio, managing scope, budget, timelines, and client relationships for each project. As her knowledge grew within the pharmaceutical industry, she transitioned to clinical aervices as a business projects manager where she headed complex strategic projects from initiation through completion. In this role Lyn exceled, working at the forefront of strategic project planning, risk management and resource balancing to lead cross functional teams to achieve global business goals. This in turn led to a promotion to Just In Time Manufacturing Solutions Manager in August 2021.