Quick Reference: FDA vs. EMA Post-Approval Changes
| Change Type | FDA Submission | FDA Timeline | EMA Submission | EMA Timeline |
|---|---|---|---|---|
| Minor admin changes | Annual Report | Within 60 days of anniversary | Type IA Notification | Implement immediately, notify within 12 months |
| Minor quality changes | CBE-30 (Changes Being Effected) | 30 days before implementation | Type IA/IB Variation | IA: immediate, IB: 30 days |
| Moderate changes | CBE-0 (Changes Being Effected) | Immediate, but FDA must be notified | Type II Variation | 60 days review (can extend to 90) |
| Major changes (new indication, formulation) | Prior Approval Supplement (PAS) | 6 months (standard) or 4 months (priority) | Type II Variation (or new MAA) | 60-90 days (or full MAA review) |
FDA Supplement Types
The FDA provides four main mechanisms for submitting post-approval changes, each with different timelines and requirements:
CBE-30: Changes Being Effected in 30 Days
Submit at least 30 days before implementing the change.
Typical Use Cases:
- •Changes to analytical procedures (e.g., new HPLC method)
- •Addition of new manufacturing site (non-sterile)
- •Extension of expiration dating period (with supporting stability data)
- •Changes to labeling (minor safety updates)
Required Documentation:
⏱️ DossiAIr Timeline:
CBE-0: Changes Being Effected Immediately
Implement change immediately, but notify FDA at time of implementation or annual report.
Typical Use Cases:
- •Addition of new safety information to labeling (black box warnings)
- •Deletion of false, misleading, or unsupported labeling claims
- •Urgent quality/safety-related manufacturing changes
PAS: Prior Approval Supplement
FDA must approve before implementation. Full review process similar to original NDA.
Typical Use Cases:
- •New Indication: Expanding drug use to new patient population or disease
- •New Dosage Form: Tablet → Injectable, IR → ER
- •New Manufacturing Site: Sterile products or API manufacturing
- •Major Formulation Change: Change in active ingredient, strength, or excipients affecting bioavailability
- •New Route of Administration: Oral → IV, topical → transdermal
Required Documentation (Extensive):
Clinical (if applicable)
- • Pivotal efficacy studies
- • Safety studies
- • Pharmacokinetic data
CMC (Quality)
- • Updated Module 3 (full S-P sections)
- • Comparability protocols
- • Validation data
⏱️ Timelines:
Annual Report
Yearly compilation of minor changes, stability data updates, and post-market safety information.
What to Include:
- •Summary of all distributed units (domestic and export)
- •Labeling currently in use
- •Summary of significant new information (adverse events, stability)
- •Status of ongoing post-marketing studies
- •Log of outstanding regulatory business (supplements pending, FDA requests)
📅 Deadline:
Within 60 days of the anniversary date of NDA approval
EMA Variation Types
The European Medicines Agency (EMA) classifies post-approval changes into three types based on risk and complexity:
Type IA: Immediate Notification
Minor changes with no significant impact. Implement immediately, notify within 12 months.
Examples:
- •Administrative changes (contact details, company name)
- •Minor editorial changes to labeling (typos, formatting)
- •Deletion of manufacturing site no longer in use
Type IB: 30-Day Notification
Minor changes requiring competent authority notification before implementation.
Examples:
- •Minor changes to synthesis of API
- •Changes to test procedures (with equivalent or better sensitivity)
- •Extension of shelf life (with supporting data)
⏱️ Timeline:
Submit → Wait 30 days → Implement (unless rejected)
Type II: Full Assessment
Significant changes requiring full regulatory assessment before implementation.
Examples (Similar to FDA PAS):
- •New therapeutic indication
- •Change in manufacturing process potentially affecting quality
- •Major changes to specifications
- •New pharmaceutical form or strength
⏱️ Assessment Timeline:
Supplement Generation with DossiAIr
🤖 Intelligent Change Detection
DossiAIr automatically compares your current approved dossier with proposed changes to determine the appropriate submission type.
✅ What DossiAIr Generates
- •Cover letter with change description and justification
- •Annotated labeling (track changes showing edits)
- •Updated eCTD modules (only affected sections)
- •Cross-reference updates across all modules
- •Validation report (eCTD structure, links)
⚡ Time Savings
Automate Your Post-Approval Changes
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