The single biggest challenge facing advanced therapies — the category once known narrowly as cell and gene therapy but now expanded to cover newer platforms including mRNA, engineered bacteriophage, and gene editing technologies — is manufacturing and scale-out. Understanding why requires understanding how fundamentally these therapies differ from the traditional biopharmaceutical manufacturing model that preceded them.
Why Does Patient Survival Depend on Logistics, Not Just Manufacturing Quality?
Cell and gene therapies are only effective if the cells or genetic material survive the full journey from manufacturing through transport, supply chain handling, and ultimately to the point of patient administration. This requirement extends well beyond simply manufacturing a high-quality product — viability at the point of use is just as critical as viability at the point of manufacture, which means logistics and supply chain design become inseparable from manufacturing strategy in a way that has no real precedent in traditional small-molecule or even traditional biologics manufacturing.
Why Doesn’t the Traditional Centralized Manufacturing Model Work for Advanced Therapies?
The traditional biopharmaceutical manufacturing model relies on a centralized footprint: large facilities capable of producing substantial quantities of stable material that can then be distributed broadly to serve large patient populations. This model scales efficiently when demand increases, because a centralized facility can typically expand output without fundamentally rethinking its distribution strategy.
Advanced therapies frequently cannot use this model, because the material involved is either freshly manufactured for immediate use or carefully cryopreserved to maintain viability — and in either case, the material must remain in close physical proximity to the patient or clinical site to preserve its therapeutic integrity. A centralized manufacturing facility serving patients across a wide geography introduces exactly the kind of extended transport and handling time that threatens product viability, which means the traditional centralized model that works well for traditional biologics becomes a liability rather than an efficiency for many advanced therapy modalities.
What Alternative Manufacturing Models Are Emerging?
In response to this fundamental constraint, advanced therapy manufacturers are increasingly exploring alternative models designed around proximity to the patient rather than centralized production efficiency. The “hub and spoke” model is one prominent approach, in which a central facility handles certain manufacturing or processing steps while smaller, geographically distributed “spoke” facilities — potentially located closer to treatment centers — handle final processing or formulation steps closer to the point of patient administration. This model attempts to capture some of the efficiency benefits of centralization while addressing the proximity requirements that pure centralization cannot satisfy.
Outsourced manufacturing through contract manufacturing organizations, or CMOs, represents a second major response to this challenge. Rather than building extensive geographically distributed manufacturing infrastructure internally — a capital-intensive undertaking — many advanced therapy developers are instead partnering with CMOs that have already built, or are building, the specialized manufacturing capabilities and geographic footprint required to support proximity-dependent production at the scale advanced therapies demand.
What Does Risk Assessment Look Like for Advanced Therapy Manufacturing and Supply Chain?
Given these constraints, risk assessment and mitigation planning have become central considerations for advanced therapy manufacturing strategy in a way that goes beyond traditional biopharmaceutical risk planning. Developers must account for the demand that material remain fresh or carefully cryopreserved, the complete shift in logistics and patient delivery models this requires relative to traditional biologics, and the operational complexity introduced by hub-and-spoke or CMO-dependent manufacturing networks, where a disruption at any single node can have outsized consequences given the proximity-dependent, time-sensitive nature of the product.
The most severe and structurally unique risk in this category is what’s often called “lot-of-one” risk: for autologous cell therapies, the starting material is the patient’s own cells, which means there is no dual-sourcing strategy available, no backup supplier, and no way to qualify a second source the way a traditional manufacturer would mitigate a critical raw material risk. If that single starting material is compromised — during collection, during transport to the manufacturing facility, or during processing — there is frequently no way to simply manufacture another batch from a different source the way a traditional biologics manufacturer could. This single fact reshapes nearly every other risk mitigation decision in advanced therapy manufacturing, from the rigor applied to chain-of-custody tracking during patient material collection and transport, to the redundancy built into cryopreservation and cold-chain logistics, to the time pressure inherent in vein-to-vein timelines where the manufacturing window itself becomes a risk factor if a patient’s clinical condition changes while their therapy is still in process.
This is a complete shift in both logistics and patient delivery thinking relative to the traditional biopharmaceutical playbook — one that requires advanced therapy developers to build manufacturing and supply chain strategy in parallel with clinical development, rather than treating manufacturing scale-out as a problem to solve only once clinical efficacy has already been established.
What Does This Mean for Advanced Therapy Developers Today?
Developers entering advanced therapy manufacturing for the first time benefit from recognizing early that the manufacturing and supply chain challenge here is not a scaled-up version of traditional biologics manufacturing — it is a structurally different problem requiring structurally different solutions. Decisions about manufacturing model, whether centralized, hub-and-spoke, or CMO-dependent, have downstream consequences for everything from clinical trial site selection to eventual commercial distribution strategy, which means these decisions are most effective when made deliberately and early, rather than inherited by default from manufacturing approaches built for a different category of therapeutic altogether.
This is also why advanced therapy manufacturing risk cannot be fully delegated to a single function. Lot-of-one risk, hub-and-spoke logistics risk, and vein-to-vein timeline risk each touch clinical operations, manufacturing, and supply chain simultaneously — a chain-of-custody failure during patient material collection is as much a clinical operations problem as it is a manufacturing one. Developers who build cross-functional risk ownership into their advanced therapy programs from the outset, rather than treating manufacturing risk as a problem owned solely by the manufacturing organization, are better positioned to catch and respond to the kind of risk that doesn’t respect traditional functional boundaries.