As the FDA notes, many IND delays can be tied to CMC challenges.

Quite often, warning signs are visible

– analytical methods that are good enough but hard to scale
– process steps that rely on the skills of an operator or one site
– issues on stability or delivery that are shelved into future work.
Such considerations are important but often get buried under everyday urgency. They could resurface as a quiet hesitation: “we’re on track for IND, however…,” That’s where our real CMC risk lies.

Premortem

A simple premortem can help as we approach regulatory filings:
What are the items that would embarrass us if a regulator asked about them tomorrow. This can serve as our CMC risk backlog and can be employed for any regulatory filing.

If you work on INDs, I’d love to hear: What do you see as the most underrated CMC risk?

Sources:
FDA CBER OTP Town Hall: Cell Therapy CMC Readiness for Late-Stage INDs
Pitfalls of Chemistry, Manufacturing, and Controls in IND Preparation
ICON – CMC in Drug Development and LCM
CMC and Analytical Gaps in CRLs: Why They Persist Despite FDA Guidance and How You Can Position Yourself for Success