Failure to charge (place) stability samples as per the approved protocol is a significant GMP deviation that may compromise product shelf life justification and regulatory compliance. A structured risk assessment is essential to evaluate the impact and determine appropriate corrective and preventive actions (CAPA).
🧭 Key Risk Areas to Assess
🔬 1. Product Quality Impact
- Was the product already distributed or released?
- Is there any other batch/study that covers similar data?
- Are worst-case conditions covered by other samples?
- Could the missing sample affect critical quality attributes (CQAs)?
📅 2. Regulatory Impact
- Is the batch part of a regulatory filing or annual stability commitment?
- Could this result in a data gap in product shelf-life justification?
- Will it impact ongoing or upcoming submissions (e.g., ANDA, NDA)?
📈 3. Compliance Risk
- Breach of ICH Q1A(R2) stability requirements
- Non-compliance with SOP or Stability Protocol
- Risk of audit observation (FDA, MHRA, etc.)
🧪 4. Scientific Justification
- Are stability trends available from other batches?
- Is a matrixing/bracketing approach applicable?
- Was the product stored under recommended conditions regardless?
👷♂️ 5. Human/Process Error
- Identify root cause (e.g., manual tracking error, system failure, training gap)
- Assess failure in scheduling, documentation, or sample accountability
⚙️ Risk Assessment Tool (FMEA or Qualitative)
| Risk Element | Assessment |
|---|---|
| Severity (S) | High (for regulatory filing batches) |
| Occurrence (O) | Medium to High (if process is manual) |
| Detection (D) | Low (if not detected until late) |
| Risk Priority Number (RPN) | S × O × D → Use to prioritize CAPA |
✅ Recommended CAPA
- Immediate Actions:
- Inform QA and Regulatory Affairs
- Log deviation and perform impact assessment
- Update stability inventory and tracking system
- Corrective Actions:
- Add a replacement batch/sample if feasible
- Provide justification in the stability report
- Inform regulators if required
- Preventive Actions:
- Automate tracking systems
- Review training effectiveness
- Enhance SOP for sample charging and verification
📋 Documentation Must Include
- Date of omission discovery
- Protocol details (batch, conditions, time point)
- Root cause and impact assessment
- CAPA plan and responsible persons
- QA and regulatory review and approval
