From Flexibility to Readiness: What CGT Teams Need to Do Differently

In her monthly column "Cell Notes," AABB's Christina Celluzzi, PhD, MS, CABP(H), shares insights, findings and commentary on emerging topics in biotherapies. This piece launches a three-part “Cell Notes” series examining how regulatory flexibility is reshaping cell and gene therapy (CGT) development, delivery and the workforce that supports it. Subscribe to CellSource to receive "Cell Notes" and biotherapies updates from AABB directly in your inbox. 

This is the second piece in our three-part “Cell Notes” series on regulatory flexibility in CGT.

In a previous “Cell Notes” piece, I explored how FDA’s emphasis on regulatory flexibility reflects the iterative nature of CGT development. This installment focuses on what that shift means for day-to-day operations, particularly for organizations navigating continuous change.

Even for readers joining here, the core concept is straightforward. CGT development evolves continuously, and regulatory pathways increasingly expect teams to evolve with it.

In flexible pathways, readiness is no longer defined by early perfection. Instead, it is defined by the ability to explain, justify and control change as knowledge grows. This distinction highlights clear differences between programs that advance smoothly and those that struggle.

Programs that struggle often treat flexibility as permission to defer structure. Common challenges include incomplete documentation of why changes were made, limited alignment across clinical, manufacturing and quality teams, and delayed regulatory engagement. When decisions are not clearly captured or communication is inconsistent, flexibility can quickly become uncertainty.

Programs that succeed tend to demonstrate three core practices:

• Intentional phase-appropriate decision making: Early processes are fit for purpose rather than more complex than needed. Teams understand critical quality attributes, assess risk, distinguish what must be controlled early from what can evolve, and document those decisions clearly.

• Robust change-management discipline: Process changes, assay refinements and manufacturing improvements are planned, justified, tracked and communicated. Comparability becomes an ongoing practice rather than a one-time milestone.

• Early, constructive regulatory engagement: Teams use regulatory interactions to test assumptions and align expectations before changes are finalized, reducing downstream delays and surprises.

These practices reflect a broader workforce shift. CGT professionals across development, manufacturing, quality and clinical roles are increasingly expected to understand not only what is changing, but why it matters and how it affects patient outcomes.

Flexibility does not reduce accountability. It heightens it. Adaptive pathways place greater responsibility on teams to demonstrate control through knowledge, data and disciplined execution.

Sustaining this level of readiness over time depends not only on systems and processes but on the resilience of the CGT workforce itself.