Biotechs are increasingly hitting a wall — not with trial design, not with patient recruitment, but with CMC bottlenecks that stall IND submissions and derail timelines. In 2025, as the FDA increases scrutiny over manufacturing and analytical controls, Chemistry, Manufacturing, and Controls (CMC) has emerged as one of the most underrated risks to clinical momentum.
What Is CMC and Why It’s Now a Top Priority
CMC encompasses the drug substance, drug product, and all processes ensuring quality, safety, and consistency. Regulatory authorities require detailed CMC documentation before greenlighting trials or approving biologics.
In 2024, FDA data showed that over 33% of clinical holds stemmed from CMC deficiencies — a figure that has only increased in early 2025.
CMC Issues Delaying Clinical Trials Today
- Incomplete comparability data after a manufacturing site change
- Instability in drug formulation, especially in biologics
- Analytical method gaps that fail to meet FDA standards
- Poorly defined control strategies for novel modalities like mRNA or ADCs
One biotech in Cambridge recently lost 8 months of trial momentum due to unresolved CMC questions around a lyophilized formulation intended for Phase 1.
Why CMC Risk is Now a Business Risk
Traditionally, biotech BD and investment teams saw CMC as a late-stage concern. That mindset no longer works.
Today:
- VCs are scrutinizing CMC readiness during due diligence
- Pharma partners delay deals over CMC data gaps
- Regulatory delays kill first-mover advantage
Tracking clinical momentum now means watching not just trial activity, but upstream manufacturing readiness.
How Sponsors Can Get Ahead
To avoid being blindsided by CMC disruptions, sponsors should:
1. Integrate CMC Planning Early
Involve manufacturing and analytical teams during preclinical development, not post-IND.
2. Conduct CMC Gap Assessments
Especially after:
- Tech transfers
- Formulation changes
- Scale-up from lab to GMP
This proactive approach can prevent last-minute FDA questions that stall trials.
3. Monitor CMC-Linked Trial Holds
Platforms like Trialonic can track delays across competitors and flag risks tied to CMC submissions, giving your team a competitive edge in forecasting.
4. Collaborate With CDMOs Strategically
Not all Contract Development and Manufacturing Organizations (CDMOs) are created equal. Choose partners that:
- Have GMP-compliant capabilities
- Offer regulatory documentation support
- Provide supply chain visibility from clinical to commercial
5. Audit CMC Readiness for Every Milestone
Build CMC checkpoints into your go/no-go decisions — not just clinical milestones, but:
- IND filing
- First-patient-in
- End of Phase 1
📈 Bottom Line
In 2025, clinical trial momentum is not just about site activation or enrollment — it’s about manufacturing foresight. Sponsors who integrate CMC strategy early and monitor competitor delays can turn operational risk into a strategic advantage.
