For years, CMC readiness could sometimes be interpreted relatively simply: can the organisation manufacture enough material, release it and move the programme forward?
That definition is changing.
Advanced therapy developers are increasingly being asked to demonstrate not simply that their manufacturing process works, but that they understand why it works, how it may need to change and whether it can withstand the demands that come with later-stage development.
Jacob Smith argued that expectations surrounding CMC readiness have evolved significantly.
Historically, a process might have been considered successful if sufficient material could be produced using available release methods. That approach may succeed for an individual campaign, but it does not necessarily demonstrate that the model can scale.
Today, discussions around products entering Phase I and II increasingly involve concepts such as critical quality attributes, quality target product profiles and clearly defined processes much earlier.
That does not mean every early-stage programme needs the fully characterised process required for commercial launch.
It does mean organisations should begin contextualising product performance against what a future scalable process may need to look like.
Núria Gavaldà offered an especially useful definition of readiness: the ability to absorb change without losing control.
That shifts CMC readiness away from a narrow manufacturing question.
A therapy may be technically GMP compliant, but that does not automatically make it affordable, scalable or accessible. Developers must consider the broader manufacturing environment, including logistics, supply chains, cost and time.
Change is inevitable. The more important question is whether the development strategy has been designed to accommodate it.
Smith argued that the industry should therefore reconsider the way it thinks about comparability and process change.
Historically, comparability could become a reactive exercise — something undertaken after a process problem forced an organisation to make a change.
A more mature approach is to recognise from the outset that a Phase I process may not be identical to the process eventually required for pivotal development or commercialisation.
Developers can then identify likely development levers in advance.
What additional process understanding will be required? Which analytical capabilities need to mature? Which product attributes need further characterisation?
Change then becomes part of strategy rather than evidence that something has gone wrong.
The discussion also exposed one of the sector's most difficult tensions.
Regulators can sometimes offer flexibility that allows an early-stage product to enter the clinic despite an immature process. In the short term, that flexibility may appear extremely valuable, particularly when funding depends on generating clinical proof of concept.
But regulatory permission to move forward does not necessarily mean a process is commercially ready.
If fundamental manufacturing problems are postponed rather than resolved, they can return later at considerably greater cost.
That is why decisions around internal and external manufacturing need to be taken seriously.
Building internal manufacturing capability represents a major commitment. Outsourcing manufacturing also requires careful partner selection and a clear understanding of responsibilities.
Neither model eliminates the need for early process thinking.
CMC readiness in 2026 is therefore becoming less about reaching a single development checkpoint and more about creating a process capable of evolving responsibly.
The goal is not to prevent change.
It is to understand the product and process well enough that change can happen deliberately, with clear knowledge of the consequences.
For advanced therapies, that may be the real definition of robustness: not creating a process that never changes, but creating one that can change without losing control.
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