pediatric-clinical-research/SOPs/SOP-002-CAPA.md

# Standard Operating Procedure: Corrective and Preventive Action (CAPA)

| Document ID | SOP-002 |
|-------------|---------|
| Title | Corrective and Preventive Action |
| Revision | 1.0 |
| Effective Date | [DATE] |
| Author | [AUTHOR] |
| Approved By | [APPROVER] |
| Department | Quality Assurance |

---

## 1. Purpose

To establish a systematic process for identifying, investigating, correcting, and preventing nonconformities and potential nonconformities in pediatric clinical research operations.

## 2. Scope

This procedure applies to:
- Product and process nonconformities
- Protocol deviations and violations
- Adverse events requiring corrective action
- Audit findings (internal, sponsor, regulatory)
- Customer/sponsor complaints
- Process deviations
- IRB/Ethics Committee findings
- Potential nonconformities identified through risk analysis
- Child safety concerns requiring systemic response

## 3. Definitions

| Term | Definition |
|------|------------|
| Corrective Action | Action to eliminate the cause of a detected nonconformity |
| Preventive Action | Action to eliminate the cause of a potential nonconformity |
| Root Cause | Fundamental reason for a nonconformity |
| Effectiveness Check | Verification that implemented actions achieved desired results |
| Protocol Deviation | Unplanned departure from protocol requirements |
| Protocol Violation | Serious protocol deviation that may impact participant safety or data integrity |

## 4. Responsibilities

### 4.1 CAPA Owner
- Investigates the issue
- Identifies root cause
- Develops and implements corrective/preventive actions
- Verifies effectiveness
- For pediatric safety issues, escalates immediately

### 4.2 Quality Assurance
- Manages CAPA system
- Assigns CAPA numbers
- Tracks CAPA status
- Reviews and approves CAPAs
- Reports CAPA metrics to management
- Monitors trends affecting pediatric participant safety

### 4.3 Principal Investigator
- Reviews CAPAs related to study conduct
- Determines if protocol deviations/violations require CAPA
- Reports to sponsor and IRB/Ethics Committee as required
- Ensures child safety concerns are addressed

### 4.4 Management
- Provides resources for CAPA implementation
- Reviews CAPA trends
- Ensures timely closure
- Escalates pediatric safety concerns to appropriate authorities

## 5. Procedure

### 5.1 CAPA Initiation

1. Identify nonconformity or potential nonconformity through:
   - Internal/external audits
   - Protocol deviations
   - Adverse events
   - Sponsor monitoring
   - IRB findings
   - Participant/family complaints
   - Quality metrics

2. Document issue on CAPA Form (FRM-003)

3. Classify severity and priority:
   - **Critical**: Immediate threat to child safety or data integrity
   - **Major**: Significant impact on quality or compliance
   - **Minor**: Limited impact, easily correctable

4. For pediatric safety concerns:
   - Immediate interim measures implemented
   - Principal Investigator and Medical Monitor notified
   - IRB/Ethics Committee notification per requirements

5. Assign CAPA owner

### 5.2 Investigation

1. Gather relevant data and evidence:
   - Study records and source documents
   - Interview personnel and families involved
   - Review environmental factors
   - Consider age-specific factors

2. Review related documents and records:
   - Protocol and protocol amendments
   - Informed consent/assent documents
   - Training records
   - Prior CAPAs

3. Use appropriate investigation tools:
   - 5 Whys
   - Fishbone (Ishikawa) Diagram
   - Failure Mode and Effects Analysis (FMEA)
   - Timeline analysis

### 5.3 Root Cause Analysis

1. Identify potential root causes, considering:
   - Human factors (training, fatigue, workload)
   - Process failures
   - Equipment or facility issues
   - Communication breakdowns
   - Pediatric-specific factors (age-appropriateness, family dynamics)

2. Verify root cause through evidence

3. Document root cause determination

4. Consider systemic implications:
   - Impact on other studies or sites
   - Need for system-wide changes
   - Regulatory reporting requirements

### 5.4 Action Development

1. Develop corrective/preventive actions that address root cause

2. For pediatric research CAPAs, consider:
   - Impact on child participants (current and future)
   - Changes to assent/consent processes
   - Age-appropriateness modifications
   - Family communication needs
   - IRB/Ethics Committee approval requirements

3. Assign responsibilities and due dates

4. Assess actions for:
   - Appropriateness to problem severity
   - Impact on other processes and studies
   - Resource requirements
   - Regulatory implications

5. Obtain necessary approvals:
   - Quality Assurance
   - Principal Investigator
   - Sponsor (if applicable)
   - IRB/Ethics Committee (if required)

### 5.5 Implementation

1. Execute approved actions per timeline

2. Document implementation evidence

3. Update affected documents/processes:
   - Revise SOPs
   - Update training materials
   - Modify study documents (with IRB approval)

4. Provide training as needed:
   - Staff training on changes
   - Refresher training if knowledge gaps identified

5. Communicate changes to:
   - Study team members
   - Sponsor
   - IRB/Ethics Committee
   - Participants/families (if applicable)

### 5.6 Effectiveness Verification

1. Define effectiveness criteria (measurable outcomes)

2. Establish verification timeframe:
   - Minimum 30 days for routine CAPAs
   - Shorter for critical safety issues with ongoing monitoring

3. Collect and analyze data:
   - Review metrics
   - Monitor for recurrence
   - Audit compliance

4. Document verification results

5. If ineffective:
   - Reopen CAPA for further action
   - Perform additional root cause analysis
   - Develop alternative actions

### 5.7 Closure

1. Review all CAPA documentation for completeness

2. Verify all actions completed

3. Confirm effectiveness verified

4. Obtain Quality Assurance approval for closure

5. Document lessons learned

6. Update risk assessments if applicable

## 6. Special Considerations for Pediatric Research

### 6.1 Child Safety Issues
- Immediate action required for any threat to child safety
- Principal Investigator and Medical Monitor notification
- IRB/Ethics Committee and regulatory authority notification per timelines
- Parental notification process activated
- Consider Data Safety Monitoring Board (DSMB) review if applicable

### 6.2 Assent/Consent Issues
- Any CAPA affecting informed consent or assent requires IRB approval
- Age-appropriateness concerns addressed by pediatric specialist
- Updated documents require re-consent/re-assent per regulations

### 6.3 Family Communication
- Transparent communication with affected families
- Age-appropriate explanations for child participants
- Cultural sensitivity in communications

## 7. CAPA Metrics

Quality Assurance shall track and report:
- Number of open CAPAs
- CAPA aging (days open)
- On-time closure rate
- Effectiveness rate
- CAPAs by category/source:
  - Protocol deviations/violations
  - Adverse events
  - Audit findings
  - Pediatric safety concerns
- Repeat/recurring issues

## 8. Related Documents

- FRM-003 CAPA Form
- SOP-004 Internal Audit
- SOP-REG-001 Regulatory Reporting
- SOP-SAF-001 Pediatric Safety Monitoring
- SOP-PED-004 Protocol Deviation Management

## 9. References

- ICH-GCP E6(R2) Section 5.20 (Noncompliance)
- 45 CFR 46.103 (Assurance of Compliance)
- 21 CFR 312.56 (Review of Ongoing Investigations)
- ISO 13485:2016 Section 8.5 (Improvement)

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## Revision History

| Rev | Date | Description | Author |
|-----|------|-------------|--------|
| 1.0 | [DATE] | Initial release | [AUTHOR] |