sNDA Alignment 101: Module 2.5, CCDS, and Labeling

 

Why you are seeing all these documents in an sNDA 

An sNDA proposes a change to an already‑approved product, most often a change to the label. FDA therefore expects a clear, traceable story that explains: 

  • What is changing 

  • Why it should change (based on new data) 

  • Where that change is reflected in the submission 

This is why Module 2.5, CCDS, and US labeling (USPI) are all developed together. 

 

The roles of each document (plain language) 

1. Module 2.5 – The scientific story 

What it is: 

  • A high‑level clinical overview written for FDA reviewers 

  • Explains the totality of evidence (new studies, ISS, RWE, literature) 

  • Describes benefit–risk and why the proposed label change is justified 

What it is NOT: 

  • It does not contain final label wording 

Think of Module 2.5 as: “Here is the clinical reasoning that supports the label we are proposing.” 

 

2. CCDS – The company’s global position 

What it is: 

  • The Company Core Data Sheet 

  • Internal master label used to support all countries 

  • Source for USPI, EU SmPC, and other local labels 

Why it matters in an sNDA: 

  • Ensures the company’s position is globally consistent 

  • May be broader than the US label, but differences must be intentional 

 

3. USPI (Labeling) – What FDA actually approves 

What it is: 

  • The official U.S. Prescribing Information 

  • What clinicians see and prescribe from 

Key rule: 

Every meaningful statement in the USPI must be supported by Module 2.5 and the underlying data. 

 

How these pieces connect (simple flow) 

     Clinical Data(Module 5)

           ↓ 

    Module 2.5 – Clinical interpretation & benefit–risk 

            ↓ 

   CCDS – Company core position 

             ↓ 

     USPI – FDA‑approved U.S. label 

If something appears in the label, FDA expects to see: 

  • A clear explanation in Module 2.5 

  • Supporting analyses in Module 5 

 

What “alignment” means in practice 

Alignment does not mean identical text. 

Alignment means: 

  • The label does not go beyond what Module 2.5 supports 

  • The tone and conclusions are consistent 

  • Any differences between CCDS and USPI are explained and justified 

 

Common alignment checks (what reviewers look for) 

High‑risk label sections 

  • Indications & Usage – Is the population and claim clearly justified in 2.5? 

  • Clinical Studies – Does 2.5 explain why these studies support labeling? 

  • Safety / Adverse Reactions – Does 2.5 summarize safety the same way the label presents it? 

Common problems 

  • Label sounds more confident than Module 2.5 

  • Safety numbers appear in labeling but are not clearly explained in 2.5 

  • CCDS and USPI differ without stated rationale 

 

One‑sentence takeaway (for non‑regulatory teams) 

Module 2.5 explains why the label should change, CCDS defines the company’s overall position, and the USPI is the FDA‑approved expression of that position. 

 

Why this matters 

Strong alignment: 

  • Reduces FDA questions and late‑cycle rework 

  • Speeds review and approval 

  • Ensures a defensible, consistent regulatory story 

Misalignment: 

  • Triggers FDA clarification requests 

  • Delays approval 

  • Creates internal rework across teams 


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