From Capacity to Coordination: The Hidden Bottleneck in Scaling CGT

As recently as a few years ago, the discussions we were having about how to scale cell and gene therapies (CGTs) primarily centered on whether manufacturing could keep up with demand. At the time, that was a real constraint. Process development was still evolving, and it wasn’t uncommon for tech transfer to take longer than expected. Frequently, available capacity didn’t align with the reality of clinical timelines. Programs would stall, but for reasons that were easy to point to. 

That type of constraint still exists today, but it’s no longer the primary constraint determining how quickly (or cleanly) a program moves forward once it reaches later-stage development. Manufacturing can usually be addressed with investment and time, but what proves harder to correct is the end-to-end supply chain that surrounds it. 

As programs grow from pre-clinical development into clinical trials and toward commercialization, the work spreads across a wider network of sites and systems. Some of those systems sit within the organization directly, but many do not. The separation between them is easy to overlook early on and becomes harder to ignore later. 

Delays in today’s CGT environment rarely begin as a single failure. They tend to emerge as a gradual loss of alignment across that broader network. In most cases, that lack of alignment can be traced back to decisions that made sense when they were made but were never intended to extend beyond the conditions under which they were created. 

How CGT Supply Chains Actually Get Built

Most supply chains in CGT are not engineered as a single project from front-to-back. They are assembled in a needs-based way over time. 

Early decisions are often driven by urgency and practicality. A collection site is supported with the beginning tools and processes it needs to operate because the team is focused on first-in-human (FIH). A logistics provider is selected because they’re local and can move material from collections to manufacturing quickly. Biostorage is arranged where capacity is available. Manufacturing partners define how they prefer to receive material (and how far in advance), and the upstream steps adjust accordingly. 

In a similar way, fresh leukapheresis-derived starting material often becomes the default for many programs because it’s familiar. It also allows teams to avoid introducing additional processing steps (like cryopreservation). When programs are in the early stages with limited volumes and closely coordinated collections and manufacturing, that approach is manageable. 

Likewise, kits are configured based on what individual sites need to function, and it’s not uncommon for collection kits to be developed to meet the needs of the initial collection site supporting FIH. Similar, need-based processes govern packaging selection, documentation approach, and the overarching quality standards. Each of these decisions is reasonable within its own context. 

What’s missing, however, is the need for those decisions to align with each other beyond what is required to keep the program moving. In the early stages of development, there is little pressure to standardize how starting material is preserved, how kits are configured across sites, or even how shipping lanes are defined and qualified, as long as the immediate objective is met and the program is on track to meet the next milestone. 

The supply chain functions because it is small enough in the early stages to be coordinated directly. The downside of this is that the direct coordination that feels like normal, everyday operations is masking how dependent the end-to-end workflows are on that coordination. 

What Changes at Scale

The first pressure shows up when the same workflow has to run across multiple sites. 

Fresh workflows for starting materials that worked under tight coordination now have to align across multiple schedules between patients, collection sites, and manufacturing slots. As shipping lanes increase, variability in geography, carrier, and handling conditions adds uncertainty. 

Kitting and site support follow a similar pattern. Collection kits or manufacturing kits that were configured to fit the needs of individual locations now need to function consistently across a network. 

When independent pieces begin operating together, variability is introduced. The supply chain still works, it just requires more intervention to keep it aligned. 

Where Inefficiency Actually Lives

By the time a program is running across multiple sites (and often within multiple geographies), the supply chain has effectively become a series of handoffs that require constant alignment. 

The effort this takes is rarely visible in planning, but shows up in how programs run day to day. A clinical trial manager who previously worked with a single collections site, single manufacturing facility, and within a single shipping lane, now needs to coordinate patient schedules within a network of collection sites, and then work within various shipping lanes to move the material to manufacturing to maximize utilization of pre-booked manufacturing slots. Or quality teams gather documentation from various disconnected vendor systems to maintain audit-ready records. 

Individually, any one of these tasks seems manageable. The issue is that they are repeated constantly, and they grow with the program. Every additional shipping lane adds another pathway that needs to be understood. Every new vendor brings its own quality framework and documentation system. 

The result is that, over time, a significant part of operational effort becomes focused on maintaining alignment across the supply chain instead of advancing the program itself. 

When Adding Capability Doesn’t Solve the Problem

As this friction becomes more visible, the natural response is to try and strengthen the individual parts of the system where weakness starts to show. 

A new logistics provider may be brought in to improve reliability for a given shipping lane. Or additional biostorage capacity is added to manage growing volume. Perhaps manufacturing partnerships are expanded to support scale. Each of these actions improves performance for a specific task within the end-to-end supply chain, but what they don’t address is how all of these elements fit together. 

A logistics provider can execute a shipment reliably within a defined shipping lane, but that doesn’t play a role in how material is prepared before it gets shipped. Biostorage can effectively store critical materials, but it doesn’t determine when or how that material is released into manufacturing. Manufacturing can run consistently, but only when materials arrive in the right condition and at a time that aligns with pre-determined availability. All of these interaction points are where the work of coordination accumulates. 

Why the System Starts Pushing Back

There is usually a point where this accumulated coordination effort begins to affect how the program progresses. 

Site activation, for example, could start to take longer than expected because collection kits, starting materials, and logistics expectations need to be aligned before work can begin. Or manufacturing schedules become difficult to maintain because the timing of inbound materials becomes less predictable across sites and shipping lanes. 

Regulatory preparation begins to reflect the same pattern. The information needed to support regulatory filings is distributed across multiple vendors and systems, and bringing it into a single submission (with audit-ready records) requires additional effort that goes beyond the underlying science. 

At this stage, most teams recognize what is happening. The difficulty lies in changing it. 

When processes are already in use, and vendors are already engaged, shipping lanes are already active, adjusting any one part of the supply chain requires coordinating across the rest. The path forward becomes a balancing act between improving what can be improved and managing what cannot be easily changed. 

What Changes When the Supply Chain is Intentionally Designed for End-to-End Integration

The fundamental issue that many CGT programs face is not complexity on its own, nor an inevitability. Rather, it’s a function of a supply chain that is operating as a collection of connected parts and not like a single, integrated model. 

When starting material is cryopreserved within a standardized workflow, materials are consistent regardless of where they are collected. When biostorage is integrated into this same workflow (and within the same vendor relationship), cryopreserved starting materials can be held and released when needed, decoupling collections from manufacturing. 

Integrating shipping into this same workflow allows for shipping lanes to be proactively defined and characterized, allowing for the movement of material to behave predictably across locations and conditions while supporting regulatory filings with documented shipping lane qualifications. 

Layering in standardized kit production for collection, manufacturing, and administration creates additional consistency as networks expand. And when these tasks are integrated into the same end-to-end supply chain managed within a single vendor relationship, all of the moving pieces streamline coordination to what is necessary rather than compensating for inconsistency. The supply chain begins to extend rather than adapt each time it grows. 

Most of the challenges associated with scaling CGTs don’t suddenly emerge at later stages. They build gradually as decisions made under early-stage conditions are carried forward into a much larger (and more interconnected) environment. 

What determines how a program behaves at scale is whether those decisions allow the supply chain to operate consistently without requiring continuous alignment between its interconnected parts. 

By partnering with an end-to-end supply chain provider like Cryoport Systems, alignment is designed into the program from the outset rather than built retroactively under pressure. Starting material is cryopreserved with IntegriCell® in a controlled, standardized workflow that decouples collection from manufacturing and allows it to be stored and released as needed. Biostorage, logistics, and kit production operate within the same framework, so material moves through qualified lanes, arrives in consistent configurations, and can enter manufacturing without adjustment. At the same time, consulting and advisory support ensure that shipping risk assessments, lane qualifications, and packaging performance are defined in advance and documented to support regulatory submissions. The result is a supply chain that behaves consistently across collection, storage, transport, and manufacturing, reducing the amount of coordination required to keep the system aligned as it scales.

The decisions made early determine whether the system scales cleanly or requires continuous correction. That is where most of the friction comes from. Not from scale itself, but from trying to operate at scale with a supply chain that was never designed to behave that way.