Guest Column | September 23, 2025

CGT Success Starts With The First Mile

By Jennifer Chain, Ph.D., CABP, cellular starting material expert

In cell and gene therapy (CGT), the patient is paramount. Efforts to deliver treatments faster and better have largely focused on therapy manufacturing, a complex bioprocess that transforms raw cells into lifesaving treatments. But this central step is framed by two equally critical stages: the first mile and the last mile, both of which impact therapy quality and delivery speed.^1,2

The last mile is a familiar concept in CGT. It begins at the manufacturing site and ends at the patient’s bedside, ensuring the right dose reaches the right individual in the right condition, at the right time.² But before a therapy ever leaves the manufacturing site, its success hinges on what happens much earlier: the first mile.

The first mile refers to the journey of cellular starting material (CSM) from a donor or patient to the manufacturing site. It’s more than logistics; it’s the foundation of therapeutic success. It begins with donor or patient qualification and includes standardized collection practices, advanced testing (e.g., flow cytometry), and processing techniques like cryopreservation. Once collected, the CSM must be handled and transported using optimized logistics to ensure it arrives in the best possible condition.¹

Whether the therapy is autologous or allogeneic, and whether manufacturing is centralized or decentralized, the first mile introduces unique biological, regulatory, and logistical checkpoints. This article focuses on why the first mile is critical to CGT success.

The First Mile Is Critical

Despite its importance, many in the CGT industry still overlook the impact of autologous and allogeneic CSM on therapy performance. Some fail to consider CSM collection as part of GMP manufacturing. Yet regulatory precedent supports GMP beginning as early as donor qualification.³ From both regulatory and technical standpoints, the first mile sets the stage for successful manufacturing and therapeutic outcomes.

The first mile is important. Here’s why:

It sets the baseline for therapeutic quality. Collected cells are living, fragile, and highly variable. If compromised by poor timing, inadequate donor selection, or suboptimal handling, no amount of downstream optimization can fix it.
It affects therapy viability. For autologous therapies, missing the optimal collection window can result in insufficient numbers of viable target cells. For allogeneic therapies, poor donor selection and qualification can jeopardize entire batches intended for multiple patients.
It drives vein-to-vein time. Especially in autologous therapies, delays in collection, testing, processing, or transport extend the overall time it takes therapies to reach patients, which is critical for those with aggressive diseases.
It underpins regulatory compliance. Product labeling, chain of custody, chain of identity, and donor screening all begin in the first mile. Mistakes in documentation can ripple through the supply chain, delaying manufacturing and increasing compliance risks.
It shapes manufacturing strategy. The strategies and logistics of the first mile influence whether centralized or decentralized models are feasible. Autologous therapies may require local collection and manufacturing, while scalable allogeneic products can tolerate longer logistics if supported by cryopreservation.

At its core, the first mile isn’t just about moving cells, it’s essential to ensure a therapy is safe, potent, and timely. Viewing the first mile as the start of manufacturing helps elevate its importance, ensuring CSM collection, processing, and shipping are treated with the same rigor as steps within the manufacturing facility.

Autologous Vs. Allogeneic: Different First Mile Realities

The first mile in CGT can vary significantly depending on whether the CSM comes from the patient (autologous) or a healthy donor (allogeneic). In autologous therapies, the journey begins with a vulnerable patient whose cells must be collected at an optimal moment in their treatment plan, adding urgency and complexity. In contrast, allogeneic therapies begin with healthy donors, shifting the focus to recruitment, qualification, and supply consistency. Each pathway presents distinct scientific, regulatory, and logistical challenges. Understanding these differences is essential to designing strategies that support safe and effective therapies.

Autologous Therapies

Autologous therapies use the patient’s own cells to manufacture the treatment,^4,5 introducing unique first mile considerations. Timing is critical because patients are often immunocompromised or are undergoing chemotherapy. Comorbidities or poorly timed collections can result in low cell counts or compromised cellular viability due to disease progression.^5,6 Sometimes, multiple collection attempts are needed, which affects the timing of processing and shipping.

“ If compromised by poor timing, inadequate donor selection, or suboptimal handling, no amount of downstream optimization can fix it. ”

Cryopreservation in autologous therapies is utilized differently from developer to developer. Some want cells shipped fresh to preserve potency, which requires rapid and reliable transport. Others use cryopreservation to decouple collection from manufacturing schedules and simplify the first mile, even if it introduces additional complexity.

Logistical urgency is also heightened during the first mile for autologous therapies. Since the cells must return to the same patient, every hour in transit matters.¹ Delays can jeopardize material quality and disrupt treatment plans. Chain of identity paperwork, which begins at collection and continues through therapy administration, ensures the therapy made from a patient’s cells is returned to that same patient without error. This meticulous tracking is a cornerstone of an effective first mile.

Allogeneic Therapies

Allogeneic therapies rely on healthy donors to provide CSM, which is then manufactured into off-the-shelf doses for multiple patients.^4,5 This model introduces a different set of first mile priorities. Developers and collectors must identify and recruit donors with ideal health histories, lifestyles, and cellular characteristics.⁵ The recruited donors undergo medical clearance, infectious disease testing, and extended qualification. Donor variability can affect therapeutic performance; therefore, a robust qualification strategy is essential. Differences in leukocyte counts, cell subset distribution, and innate cell function must be accounted for to ensure consistent quality.

Cryopreservation is increasingly common in allogeneic models.^7,8 With centralized manufacturing and geographically dispersed donors, preserving cells before shipment helps overcome transport challenges and supports inventory building. This strategy simplifies the first mile for allogeneic therapies and is especially valuable as therapies move through clinical trial phases and toward commercialization.

Regulatory frameworks for donor CSM collection are still being defined.³ It is important to align with the regulatory requirements of the specific therapy being manufactured. Maintaining custody and traceability throughout collection, processing, and shipping is one essential regulatory requirement. Chain of custody paperwork ensures compliance and continuity.¹ Errors or omissions in this documentation can compromise manufacturing and disrupt the first mile.

Manufacturing Models And The First Mile

The first mile doesn’t operate in isolation but is shaped by the manufacturing model a company adopts. The distance cells must travel, the need for cryopreservation, and how chain of custody and identity are managed all hinge on whether manufacturing is centralized in a few hubs or decentralized across regional or hospital-based sites. Each model carries trade-offs that can either amplify or mitigate first mile risks.

Centralized Manufacturing: Consistency And Control, But First Mile Challenges

Centralized manufacturing concentrates production into specialized hubs,⁹ offering advantages like highly trained staff, standardized processes, economies of scale, and strong regulatory oversight. This model is especially suited for allogeneic therapies, which require consistent, large-scale processing of donor-derived cells into off-the-shelf doses. Complex autologous therapies also benefit from this model, where access to trained staff and specialized equipment is essential. Centralized manufacturing hubs are often located near scientific centers, benefiting from access to expertise, infrastructure, and regulatory familiarity.

However, centralized models introduce challenges. Donor or patient cells often travel long distances, sometimes internationally, to reach the facility. Each hour in transit risks cell viability, particularly for fresh autologous collections that can’t afford delays. As a result, centralized models rely heavily on cryopreservation and ultra-cold transport logistics.⁹ While cryopreservation decouples collection from processing, it introduces variability in thaw recovery and demands strict handling protocols.

Operational complexity also increases with centralized manufacturing. Companies must manage global supply chains involving multiple couriers, customs checkpoints, and temperature monitoring systems. Chain of identity errors, especially in autologous workflows, can have catastrophic consequences. To mitigate these risks, companies investing in centralized models often allocate as much effort to supply chain management and logistics partnerships as they do to bioprocessing science. These investments boost both the first mile to the facility and the last mile from it.

Decentralized Manufacturing: Simplified First Mile, But With Trade-Offs

Decentralized manufacturing brings production closer to the patient, often within regional hubs or hospital-based cleanrooms.⁹ This reduces shipping time, improves cell freshness, and often eliminates the need for cryopreservation. For autologous therapies, proximity allows for greater scheduling flexibility and faster vein-to-vein time.

This model is gaining some traction in clinical trials, where hospital-based cleanrooms enable on-site manufacturing.⁹ Some companies are piloting point-of-care platforms with modular, closed-system bioreactors embedded in treatment centers, reducing logistics to an intra-campus handoff.

Yet decentralization introduces its own challenges.^9,10 Each site must maintain GMP compliance, train staff, and pass inspections, which multiply regulatory burden. Standardization across sites is difficult; even minor differences in equipment or technique can affect product comparability. Scaling across dozens of sites for commercial production is resource-intensive and costly.

Supply chain consistency is another concern. While decentralized models reduce transport risks, they may struggle to ensure uniform quality across geographies. Companies must rely on digital platforms, remote monitoring, and centralized quality systems to harmonize operations.

Ultimately, while decentralized models simplify the first mile, there are significant trade-offs in other areas of delivering quality therapies. Therefore, companies choosing this model must carefully consider all factors, not just proximity to patients and donors.

First Mile Strategies: Optimizing, Safeguarding, And Scaling

As cell and gene therapies expand, so must the strategies that support their earliest and most fragile phase. The first mile demands more than logistical coordination; it requires a deliberate multi-dimensional strategy that safeguards quality, mitigates risk, and prepares for scaling.

Operational Risk Management

To protect the integrity of vulnerable living cells, companies must implement robust operational safeguards:

Build a database of ideal donors tailored to specific therapies to reduce downstream functional variability.
Standardize collection protocols to ensure consistency in donor/patient collection, timing, and technique to reduce variability in the makeup of the CSM.
Validate handling and cryopreservation procedures to preserve cell viability and minimize variability in thaw recovery.
Align logistics planning with collection and manufacturing schedules to minimize delays and optimize vein-to-vein time.
Plan for contingencies, such as having backup couriers and shipping lanes, alternate collection sites, and emergency protocols to mitigate disruptions from weather, customs, or equipment failure.

Regulatory Alignment

The first mile is not just a logistical phase, it is the beginning of GMP manufacturing. Developers and collection centers must align with regulatory bodies accordingly:

Early GMP integration that treats donor qualification and CSM collection as regulated manufacturing steps improves audit readiness and compliance.
Product labeling and chain of identity and custody documentation systems, including barcoding, digital tracking, and real-time monitoring, prevent mislabeling and ensure traceability across all workflows.

Looking Ahead: Innovation, Collaboration, And Scalability

As CGT moves from clinical trials to commercial scale, first mile strategies must innovate:

digital platforms and AI tools to predict optimal collection windows, assess donor suitability, and forecast logistics bottlenecks,
automation and closed systems for collection and processing to reduce human error and improve reproducibility,
regional collection networks to support both centralized and decentralized manufacturing models, flexibility, and scaling efforts,
vendor qualification and training to ensure that all partners in the first mile ecosystem meet GMP standards and understand the unique demands of CGT workflows,
cross-functional integration between collection, clinical, manufacturing, regulatory, and logistics teams to ensure aligned priorities and seamless execution, and
remote monitoring and centralized quality oversight to harmonize operations across geographies and support scaling without sacrificing consistency.

Conclusion

The CGT industry has long focused innovation around manufacturing. More recently, attention has turned to optimizing the last mile to accelerate therapy delivery. But as explored here, the journey of a successful therapy begins well before the production suite. The steps in which cellular starting material is collected, qualified, and shipped set the tone for everything that follows.

Variations in the first mile occur depending on whether a therapy is autologous or allogeneic. Autologous therapies require precise timing and coordination to preserve patient-derived cells, while allogeneic therapies demand rigorous donor qualification and batch consistency.¹⁰ Each presents distinct challenges that must be addressed through tailored logistics and quality strategies.

Manufacturing models (centralized or decentralized) also shape first mile risks and opportunities. Long-distance transport, cryopreservation, and chain of identity must be weighed against proximity, scalability, and regulatory complexity.^1,9,10 Each model has trade-offs that require thoughtful planning.

By investing in first mile strategies that optimize operations, mitigate risk, and prepare for scale, CGT companies can strengthen the foundation of their therapies. From standardized protocols and digital tracking to predictive analytics and remote monitoring, it’s no longer just a logistical step, it’s a strategic priority.

Elevating the first mile to the same level of rigor and innovation as manufacturing and the last mile is essential. In CGT, the quality of a therapy is only as strong as the journey that brought it there — starting with the very first mile.

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About The Author:

Jennifer Chain, Ph.D., CABP, is a cellular therapy expert with 27 years of experience in T cell immunology, product development, blood banking, and consulting. She holds a Ph.D. in immunology and a Certified Advanced Biotherapies Professional credential from the Association for the Advancement of Blood and Biotherapies (AABB). She currently works as a consultant in the cellular starting material space, helping collection centers and cell therapy companies develop CSM collection and procurement programs as well as other strategic plans. Reach her on LinkedIn or CSM Consulting’s website, www.cellsmatter.com