Clinical Site Readiness for Cell and Gene Therapies: Operational and Supply Chain Challenges as they Scale and as they Expand into the Community Care Setting

Cell and gene therapies (CGTs) are rapidly transforming the treatment landscape for oncology, rare genetic disorders, autoimmune diseases, and other serious conditions. These therapies offer the potential for durable responses and, in some cases, functional cures that were previously unattainable with conventional treatments. However, unlike traditional pharmaceuticals, the successful delivery of CGTs requires a highly specialized environment that spans patient identification, cell collection, cryoprocessing, manufacturing, specialized packaging, temperature-controlled logistics, specialized storage, and administration.

As clinical development pipelines continue to expand and approved therapies scale, supply chain considerations are becoming increasingly critical. While manufacturing capacity had historically been viewed as the primary bottleneck, the industry is now recognizing that clinical site readiness, logistics coordination, and end-to-end supply chain coordination are emerging as equally significant constraints. This challenge is further amplified by the industry's strategic goal of expanding access beyond major academic medical centers and into community-care settings to reach the ~80% of the population that currently cannot access these therapies.

The future success of cell and gene therapies will depend not only on scientific innovation but also on the ability to build scalable, resilient, and patient-centric operational models capable of supporting significant increases in treatment volumes across a wider range of points of care.

The evolution of clinical site readiness

Historically, cell and gene therapy trials were concentrated within a small number of highly specialized academic medical centers. These institutions possess the infrastructure, expertise, and multidisciplinary teams necessary to manage highly complex therapies such as autologous CAR-T treatments, albeit at significant cost and resource requirements.

Today, the landscape is changing. More than a thousand CGT clinical trial programs are active globally, and sponsors are seeking to expand patient enrollment and commercial access through larger site networks. As a result, site readiness has evolved from a primarily clinical assessment into a comprehensive operational capability evaluation.

A modern CGT-ready site requires the physical infrastructure, including apheresis capabilities where applicable, qualified cryogenic storage, and temperature monitoring with alarm systems, alongside the process discipline to run robust ISO 21973–aligned workflows and specialized pharmacy handling. Just as critically, it depends on people and systems: trained nursing and administration staff, 24/7 patient monitoring, dedicated operational coordinators, and quality management systems that can support strong logistics, scheduling, packaging management, and IT infrastructure all at once.

Increasingly, sponsors recognize that a site's ability to manage operational complexity may be as important as its clinical expertise and they may need to move to a 3^rd party support model to increase efficiency and enable their clinical staff to focus on patient care, not supply chain needs. Even highly experienced healthcare institutions can struggle to support CGTs if operational workflows are not standardized, scalable, and supported by appropriate technology.

The growing complexity of therapy coordination

One of the defining characteristics of cell and gene therapies is the extensive coordination required across multiple stakeholders. For many personalized therapies, every patient effectively has an individualized supply chain.

A single treatment may require coordination among:

• Treating physicians
• Patient navigators
• Apheresis centers
• Site pharmacists
• Clinical research teams
• Manufacturing facilities
• Quality organizations
• Logistics and BioServices providers
• Central laboratories
• Sponsor operations teams
• Contract research organizations

Each handoff introduces risk and complexity. Manufacturing slots must align with patient readiness, collection dates, transportation schedules, product release testing, lymphodepletion regimens, and administration appointments.

In early-stage studies involving a small number of patients, these processes can often be coordinated manually. As trials scale into multicenter regional and global programs, however, manual processes become increasingly difficult to sustain. Communication gaps, scheduling conflicts, documentation errors, and shipment delays can quickly become major operational risks.

As patient volumes increase, coordination itself is emerging as a significant limiting factor to scalability. Sponsors are increasingly investing in operational command centers, dedicated therapy coordinators, and digital workflow platforms to manage this growing complexity.

Supply chain challenges in advanced therapies

The supply chains supporting cell and gene therapies are fundamentally different from those used for traditional pharmaceuticals.

For autologous therapies in particular, the supply chain is highly individualized and time sensitive. Patient cells must be collected, transported to a manufacturing facility, processed, tested, shipped back to the treatment site, and administered within defined timelines.

Several factors contribute to supply chain complexity:

Temperature-controlled logistics

Many cell therapies require cryogenic transportation and storage at temperatures below -150°C. Maintaining product integrity throughout transport requires specialized shipping systems, continuous monitoring, validated processes, and contingency planning.

Limited manufacturing flexibility

Unlike conventional medicines, there is often no replacement inventory available. If a patient-specific product is delayed, damaged, or rendered unusable, treatment schedules may be disrupted and patients may require recollection procedures.

Global transportation risks

As trials expand internationally, logistics become increasingly vulnerable to customs delays, weather disruptions, airline capacity constraints, geopolitical instability, and regional regulatory differences.

Capacity management

The challenge is no longer confined to manufacturing throughput. Capacity constraints increasingly occur across transportation networks, site storage facilities, qualified personnel availability, and administration schedules.

Collectively, these factors create a highly interconnected operational environment in which disruptions at any point in the chain can affect patient outcomes.

Regulatory expectations, standardization, and the role of iso 21973

As cell and gene therapies advance from highly controlled clinical environments toward broader commercial adoption, regulators and industry stakeholders are placing increased emphasis on supply chain standardization and transportation controls. While regulatory agencies such as the FDA, EMA, and other global health authorities maintain oversight of product quality, patient safety, chain of identity, and chain of custody requirements, industry standards are emerging to provide a common operational framework for the increasingly complex therapy delivery networks.

One of the most significant developments in this area is ISO 21973:2020, Biotechnology — General Requirements for Transportation of Cells for Therapeutic Use. The standard was developed specifically to address the unique transportation challenges associated with regenerative medicine products and outlines requirements for transportation planning, risk assessment, traceability, documentation, communication, verification, validation, and exception management throughout the transportation process.

The importance of ISO 21973 is growing as cell and gene therapy supply chains become more distributed. Unlike traditional pharmaceutical products, advanced therapies often require patient-specific handling, cryogenic storage, strict environmental controls, and precise coordination among multiple stakeholders. The standard emphasizes capabilities such as shipment tracking, monitoring, chain-of-custody controls, centralized logistics management, and supporting information technology infrastructure—all areas that have become critical as clinical programs increase in scale.

From a clinical site readiness perspective, alignment with ISO 21973 principles can help organizations establish a more robust operational framework. Sites must be able to demonstrate not only appropriate clinical competency but also the ability to support transportation risk management programs, maintain traceability throughout the therapy lifecycle, manage deviations and exceptional events, and participate in coordinated communication processes across manufacturers, logistics providers, and treatment centers. These capabilities are particularly important for autologous therapies, where every shipment represents an individual patient's treatment and where product replacement may not be possible.

The relevance of ISO 21973 becomes even more pronounced as treatment delivery expands into community care settings. Historically, a limited number of academic medical centers possessed the infrastructure and expertise necessary to manage complex cellular therapy logistics. Community-based providers, however, often have varying levels of experience with cryogenic handling, advanced biologics transportation, and chain-of-custody controls. A standardized framework such as ISO 21973 can help create greater consistency across these diverse care settings by establishing common expectations for transportation quality, documentation, operational oversight, and risk management.

Ultimately, as the industry seeks to support larger patient populations and more geographically dispersed treatment networks, compliance with recognized standards such as ISO 21973 will increasingly be viewed as a foundational component of site readiness. The ability to consistently execute transportation and logistics processes with documented traceability, validated controls, and end-to-end visibility will be critical to ensuring patient safety, regulatory compliance, and scalable access to cell and gene therapies.

Expanding cell and gene therapies into community care settings

Perhaps the most significant evolution currently underway is the industry's effort to expand access beyond major academic centers and into community care settings.

Today, many eligible patients must travel long distances to receive advanced therapies. Geographic concentration of treatment centers creates challenges related to travel burden, treatment delays, caregiver requirements, and health equity.

To address these issues, sponsors, healthcare systems, and providers are exploring pathways to decentralize elements of the treatment process.

Community-based expansion could take several forms, from local patient identification and referral to community-based monitoring, regional or outpatient apheresis collection centers, and standardized third-party cryopreservation facilities. Some models go further still, introducing shared-care treatment structures, hybrid administration networks, or distributed patient support services.

While this strategy has the potential to improve access significantly, it introduces additional operational complexity.

Community sites often have less experience managing cryogenic materials, advanced biologic handling requirements, complex chain-of-custody procedures, specialized adverse event management, and cell therapy scheduling processes.

As a result, readiness standards must be expanded beyond infrastructure assessments to encompass extensive training, operational mentoring, ongoing quality oversight, and standardized workflows.

Community care as a new supply chain node

From a supply chain perspective, expansion into community care settings fundamentally changes the network architecture supporting CGTs.

Historically, sponsors coordinated with a relatively small number of highly experienced academic centers. Community expansion introduces a much larger and more diverse provider ecosystem.

This shift creates new logistical challenges: more shipment destinations, greater variability in site capabilities, increased training requirements, additional quality oversight activities, expanded inventory visibility needs, and more complex scheduling coordination.

The supply chain must become more flexible while maintaining identical quality and compliance standards.

In effect, every newly activated community site becomes an additional node in a highly controlled and patient-specific supply network. Ensuring consistency across these sites requires significant investment in technology, process standardization, and operational support.

Digitalization as a foundation for scalability

Technology will likely play a central role in enabling both scaling and community expansion.

Digital solutions increasingly provide:

• End-to-end therapy tracking
• Manufacturing scheduling visibility
• Shipment monitoring
• Chain of identity management
• Capacity planning
• Site readiness assessments
• Quality event reporting
• Real-time stakeholder communication

These platforms help reduce administrative burden while improving transparency across the therapy journey.

As networks become larger and more geographically dispersed, digital integration will become essential. The industry is moving toward integrated ecosystems capable of connecting sponsors, manufacturers, logistics providers, treatment centers, and community partners through a single operational framework.

Conclusion

Cell and gene therapies are entering a period of unprecedented growth. While scientific innovation continues to drive new therapeutic breakthroughs, operational readiness and supply chain execution are increasingly becoming the determining factors for successful trial conduct and commercial delivery.

As treatment volumes increase, coordination challenges, chain of identity requirements, workforce constraints, logistics complexity, and site variability are emerging as significant barriers to scale. These pressures are magnified by the industry's goal of expanding access beyond specialized academic centers and into community care settings, where most patients receive treatment.

The next phase of growth in cell and gene therapies will depend on building highly coordinated networks supported by standardized processes, trained personnel, resilient logistics systems, and digital orchestration tools. Organizations that successfully address these operational and supply chain challenges will be best positioned to expand patient access, accelerate clinical development, and fully realize the promise of advanced therapies.

Mark Sawicki, PhD, president & CEO, Cryoport