Turning CMC complexity into a defined plan.
How Nexus approaches common regulatory CMC problems, through case studies and illustrative scenarios.
Case Studies
These sample case studies highlight the kinds of CMC challenges we frequently help clients overcome as they prepare for U.S. clinical trials.
Case study 1. Client Profile: Seed-stage oncology startup, no internal CMC lead
Challenge
Company was 5 months from a planned IND submission but had no formal stability plan or control strategy. Internal teams were focused on preclinical and fundraising.
Solution
Design a Phase 1-appropriate stability protocol and impurity control strategy using limited available data. Identification of key gaps, projection of ICH-aligned timelines, and coordination with CDMOs to accelerate method qualification.
Result
A complete Module 3 was delivered within 3 months. IND accepted with no CMC comments. Client secured Series A shortly after.
Case study 2. Client Profile: Preclinical stage immunology company entering Phase 1
Challenge
Client attempted a self-authored IND using CDMO templates. FDA issued a clinical hold due to inadequate specification limits and incomplete manufacturing sections.
Solution
A CMC gap assessment, rewriting of key Module 3 sections, and leading written FDA correspondence and resubmission.
Result
Hold lifted in 30 days. Client retained us long-term for strategic oversight through Phase 2 scale-up.
Case study 3. Client Profile: Virtual pharma company developing a CNS small molecule
Challenge
They had hired a CDMO and a formulation CRO, but lacked a unified regulatory strategy or plan to track critical quality attributes across sites.
Solution
Mapping of an integrated CMC development plan, defining data ownership responsibilities, and guiding the CDMO toward a clear Phase 1 deliverable package.
Result
The prevention of duplicated studies, cuts to unnecessary spending, and getting the CMC data locked 2 months ahead of the target date. IND filed with confidence.
Common CMC challenges and how we approach them.
Illustrative scenarios — These hypothetical examples show our approach. They do not describe specific client engagements or outcomes.
Hypothetical scenario 1: IND CMC readiness for an emerging biotech
Challenge
An early-stage team approaching its IND lacks a coordinated stability program and control strategy, with key data held by separate contract partners.
Our approach
Assess technical gaps against phase-appropriate expectations, align CDMO deliverables with the submission timeline, and develop a Module 3 plan.
Hypothetical scenario 2: Addressing CMC deficiencies
Challenge
Gaps in specifications and manufacturing documentation put a planned clinical study timeline at risk.
Our approach
Evaluate each deficiency, develop a prioritized remediation plan, and support preparation of responses to FDA.
Hypothetical scenario 3: Coordinating multiple development partners
Challenge
A virtual company relies on several contract manufacturers and testing laboratories, with no single owner of CMC data or documentation.
Our approach
Define data ownership and review responsibilities, align partner milestones, and establish documentation workflows that support regulatory submissions.
Hypothetical scenario 4: Transitioning from a Phase 2 to Phase 3 IND
Challenge
An emerging pharma company with successful Phase 2 data now faces the complexity of preparing for Phase 3 — which means new validation requirements, scale-up of manufacturing, and agency expectations around comparability and control strategies.
Our approach
Nexus CMC Advisors could help map out the transition, define what needs to change in Module 3, and build a Phase 3-ready CMC plan that supports both the IND and future marketing applications.
Hypothetical scenario 5: Overlooked CMC Risks Before Tox
Challenge
A startup with a solid toxicology plan may unknowingly be missing critical CMC components — like an adequate container closure strategy, formal impurity limits, or method qualification.
Our approach
We help teams prioritize must-have Phase 1 activities, while also identifying low-effort, high-impact improvements that prevent delays downstream.
Hypothetical scenario 6: Academic Spinout Without Templates or Timelines
Challenge
An academic team with a promising compound might be ready for GLP tox, but lacking any CMC document templates, quality system, or structured regulatory roadmap.
Our approach
In this case, we could offer a modular approach: building a Phase 1-appropriate Module 3, training the founding team on regulatory expectations, and guiding the transition from academic-grade to clinical-grade documentation.
Experience-based guidance for complex CMC problems.
We establish the regulatory context and development stage, identify the issues most likely to affect the next milestone, and build a plan that technical teams and partners can execute.