For CMOs and CDMOs based outside the United States, serving U.S. clients is a major growth opportunity—but it also comes with heightened scrutiny.
U.S. sponsors rely heavily on their manufacturing partners to meet FDA CMC and GMP standards, especially when preparing regulatory filings like INDs, NDAs, and BLAs.
If your site or processes fall short of FDA expectations, your client’s entire program—and your reputation—could be at risk.
Here’s what foreign CMOs must understand about getting CMC-ready for the U.S. market.
Why U.S. Regulatory Expectations Are Different
- Greater Early-Stage CMC Scrutiny: Even Phase 1 INDs require robust CMC packages.
- FDA Inspections Prior to Approval: Foreign manufacturing sites are almost always inspected pre-approval.
- High Documentation Standards: Batch records, validation protocols, and change control systems must be U.S.-ready.
- Real-Time Stability Data: FDA expects more extensive stability data than some other regulators.
In short, the FDA assumes risk until you prove otherwise.
Your data and systems must show proactive, documented control of product quality and consistency.
Key CMC Areas Foreign CMOs Must Prepare
| CMC Area | U.S. Expectation |
| Batch Records | Detailed, contemporaneous, traceable documentation |
| Process Validation | Full validation for commercial products; Phase-appropriate for clinical |
| Regulatory Starting Materials | Clear definition and justification |
| Specifications | Tight, scientifically justified limits |
| Stability Programs | Real-time data supporting retest and expiry periods |
| Facility Readiness | Readiness for Form 483 inspections and follow-up |
Best Practices for U.S. CMC Compliance
Conduct Internal GMP Audits with a U.S. Lens
- Focus on records, deviations, change controls, and OOS (out-of-specification) management.
Build U.S.-Compliant CMC Dossiers Early
- Work with clients to prepare CMC sections that meet U.S. eCTD Module 3 expectations.
Invest in Batch Record Readiness
- Ensure clear, complete, and audit-ready documentation of each manufacturing run.
Anticipate Pre-Approval Inspections
- Prepare proactively: mock inspections, CAPA (corrective action/preventive action) programs, and training are critical.
Engage U.S.-Experienced Consultants
- Don’t rely solely on home country standards. U.S. regulatory expertise will help avoid surprises during review.
Common Pitfalls to Avoid
- Assuming EU GMP = FDA GMP without gap assessment
- Submitting incomplete or poorly formatted stability data
- Overlooking container closure system integrity testing
- Delaying validation work until late in the NDA/BLA process
- Ignoring the need for English-language documentation for inspections
Final Thoughts
Winning U.S. business as a foreign CMO/CDMO isn’t just about offering manufacturing capacity—it’s about earning trust with regulatory-ready systems, data, and processes.
At DSI, we help foreign manufacturing partners and their biotech clients de-risk CMC filings, prepare for FDA inspections, and accelerate U.S. approvals.
If you're ready to expand into the U.S. market, we’re ready to support you every step of the way.
