As cell and gene therapies (CGTs) continue their transition from experimental interventions to established treatment modalities, one of the most persistent strategic debates in the industry concerns manufacturing model selection. Should CGT manufacturing be centralised in large, industrial facilities, or decentralised closer to the patient in hospital-based or regional sites?
The debate is often framed as a stark contrast. Centralised manufacturing is associated with scale, efficiency, and commercial discipline, while decentralised manufacturing is positioned as agile, patient-centric, and clinically integrated. Yet when examined through the lenses of Quality by Design (QbD), LEAN manufacturing principles, and ICH-aligned quality systems, a different conclusion emerges.
Centralised and decentralised approaches to CGT manufacturing are not really that different.
They are governed by the same manufacturing science, constrained by the same physical realities, and ultimately succeed - or fail - based on the same principles.
The common constraint: Throughput in limited space
Regardless of geography, all CGT manufacturing must contend with a fundamental challenge: delivering sufficient throughput within constrained cleanroom space, labour availability, and capital investment.
For centralised manufacturing, this requirement is self-evident. A single facility may be responsible for producing drug product for entire countries or regions. Under these conditions, low throughput density quickly translates into unsustainable cost of goods, long lead times, and supply risk.
What is less obvious, but equally true, is that decentralised manufacturing faces the same constraint, often in more compressed form. Hospital-based and regional CGT facilities typically operate within much smaller footprints, frequently embedded within existing academic or clinical infrastructure. Cleanroom space is scarce, expansion is costly, and staffing models are tightly constrained. Yet many of these facilities have demonstrated clinical success, treating patients locally and reliably. As confidence grows, demand follows. Decentralisation does not eliminate the need for throughput - it concentrates it.
A QbD perspective: Design space applies everywhere
Quality by Design, as articulated across the ICH Q-series guidelines, begins with a simple but demanding premise: quality must be built into the process through a deep understanding of how inputs, process parameters, and unit operations influence critical quality attributes.
From a QbD standpoint, throughput is not merely an operational metric - it is a process parameter that directly affects quality risk. As utilisation approaches capacity limits, variability increases, deviations become more frequent, and control strategies are stressed
This applies equally to centralised and decentralised facilities. The difference lies only in where the constraint manifests. In centralised sites, it appears as scale pressure. In decentralised sites, it appears as space pressure. In both cases, the outcome is the same: a narrowing of the effective design space.
When demand grows faster than manufacturing flexibility, quality risk accumulates regardless of facility size.
Clinical expansion exposes manufacturing fragility
Early decentralised CGT programmes were often justified on the basis of modest patient volumes and narrow indications, most commonly
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