pediatric-clinical-research/SOPs/SOP-004-Internal-Audit.md

Standard Operating Procedure: Internal Audit

Document ID	SOP-004
Title	Internal Audit
Revision	1.0
Effective Date	[DATE]
Author	[AUTHOR]
Approved By	[APPROVER]
Department	Quality Assurance

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1. Purpose

To establish a process for conducting internal audits to verify compliance with the Quality Management System, pediatric research regulations, and study protocols, and to identify opportunities for improvement.

2. Scope

This procedure applies to:

• Planned audits of QMS processes and procedures
• Study-specific audits of pediatric clinical trials
• Site audits of research facilities
• Supplier/vendor audits (if applicable)
• For-cause audits triggered by quality concerns
• Pre-study readiness assessments

3. Definitions

Term	Definition
Internal Audit	Systematic, independent examination of activities and documents
Auditor	Qualified individual conducting the audit
Auditee	Individual or department being audited
Audit Finding	Observation of noncompliance or deficiency
Observation	Opportunity for improvement not constituting noncompliance
Critical Finding	Issue that poses immediate risk to child safety or data integrity

4. Responsibilities

4.1 Quality Assurance Manager

• Develops annual audit program
• Selects and qualifies auditors
• Reviews and approves audit reports
• Tracks corrective actions
• Reports audit results to management
• Ensures pediatric-specific requirements audited

4.2 Auditors

• Conduct audits per plan and procedure
• Maintain independence and objectivity
• Document findings accurately
• Verify corrective actions
• Maintain confidentiality
• Understand pediatric research regulations

4.3 Auditee

• Cooperate with audit activities
• Provide requested documentation
• Respond to findings within timeframe
• Implement corrective actions
• Verify effectiveness

4.4 Management

• Support audit program
• Provide resources for corrective actions
• Review audit summaries
• Address systemic issues

5. Procedure

5.1 Annual Audit Program

1. Quality Assurance develops annual audit schedule considering:

   • All QMS processes audited at least annually
   • Risk-based prioritization
   • Previous audit results
   • Regulatory inspection history
   • Active pediatric studies
   • Changes to regulations or processes
   • Sponsor/customer requirements

2. Audit schedule includes:

   • QMS processes (Document Control, CAPA, Training)
   • Clinical operations (protocol compliance, safety reporting)
   • Regulatory affairs (submissions, communications)
   • Data management
   • Pediatric-specific processes (assent, parental permission, age-appropriate procedures)

3. Schedule approved by management

4. Schedule flexible to accommodate for-cause audits

5.2 Auditor Qualification

Auditors must demonstrate:

• Knowledge of QMS standards and regulations
• Understanding of pediatric research regulations (45 CFR 46 Subpart D, 21 CFR 50 Subpart D, ICH E11)
• Current GCP certification
• Audit training completion
• Independence from audited area
• Previous audit experience (for lead auditors)

5.3 Audit Planning

1. Assign auditor(s) and lead auditor

2. Ensure auditor independence (no audit own work)

3. Develop audit plan including:

   • Audit objectives and scope
   • Areas/processes to be audited
   • Audit criteria (regulations, SOPs, protocols)
   • Audit dates and estimated duration
   • Personnel to be interviewed
   • Documents to be reviewed
   • Special pediatric considerations

4. Notify auditee at least 2 weeks in advance (except for-cause audits)

5. Request documents for pre-review:

   • SOPs and work instructions
   • Training records
   • Study protocols and amendments
   • Informed consent/assent documents
   • Safety reports
   • Regulatory correspondence

5.4 Audit Execution

5.4.1 Opening Meeting

1. Introduce audit team
2. Confirm audit scope and schedule
3. Explain audit process
4. Answer questions
5. Establish logistics (workspace, access)

5.4.2 Document Review

Review documents for:

• Compliance with regulations and SOPs
• Completeness and accuracy
• Proper approvals and signatures
• Traceability
• Pediatric-specific requirements:
  • Age-appropriate consent/assent forms
  • Proper parental permission
  • Adherence to 45 CFR 46.408 categories
  • Pediatric safety monitoring
  • Growth/development assessments

5.4.3 Interviews

• Interview key personnel
• Assess knowledge of procedures
• Verify training on pediatric requirements
• Evaluate understanding of child protection principles
• Assess competence in age-appropriate communication

5.4.4 Observation

• Observe processes in action where possible
• Assess compliance with procedures
• Evaluate facility suitability for pediatric research
• Assess child-friendly environment

5.4.5 Finding Documentation

For each finding, document:

• Specific noncompliance or deficiency
• Regulatory or procedural reference
• Objective evidence
• Risk level (Critical, Major, Minor)
• Location and date observed

Critical findings (immediate child safety risk):

• Report immediately to management and Principal Investigator
• Document interim actions taken
• Escalate per safety procedures

5.5 Closing Meeting

1. Present preliminary findings

2. Discuss observations

3. Clarify any misunderstandings

4. Establish timeframe for corrective action response

5. Thank auditee for cooperation

5.6 Audit Report

1. Lead auditor prepares audit report including:

   • Executive summary
   • Audit scope and criteria
   • Areas audited
   • Documents reviewed
   • Personnel interviewed
   • Findings (Critical, Major, Minor)
   • Observations (opportunities for improvement)
   • Positive practices noted
   • Conclusion and overall compliance assessment

2. Report issued within 10 business days

3. Report distributed to:

   • Auditee
   • Auditee management
   • Quality Assurance Manager
   • Executive management (for critical findings)
   • Principal Investigator (for study audits)

5.7 Corrective Action Response

1. Auditee submits CAPA response within:

   • Critical findings: 3 business days
   • Major findings: 10 business days
   • Minor findings: 15 business days

2. Response includes:

   • Root cause analysis
   • Immediate corrective actions
   • Long-term preventive actions
   • Responsible person
   • Target completion date
   • Effectiveness verification plan

3. Quality Assurance reviews and approves response

4. If inadequate, response returned for revision

5.8 Follow-up Verification

1. Auditor verifies corrective action implementation

2. Verification methods:

   • Document review
   • Follow-up audit
   • Process observation
   • Records sampling

3. Verify effectiveness of actions

4. Document verification results

5. Close findings when satisfactorily addressed

6. If not effective, finding remains open and escalated

5.9 Audit Metrics and Reporting

Quality Assurance tracks and reports:

• Audits completed vs. planned
• Findings by type and severity
• Open vs. closed findings
• Overdue corrective actions
• Trends by area/process
• Repeat findings
• Pediatric-specific findings trends

6. Special Considerations for Pediatric Research

6.1 Assent and Consent Verification

• Review sample informed consent/assent forms
• Verify age-appropriate language
• Check IRB approval documentation
• Verify version control and participant records match
• Confirm proper signatures obtained

6.2 Pediatric Safety Monitoring

• Review adverse event documentation
• Verify growth and development monitoring
• Check pediatric-specific assessments completed
• Review DSMB reports if applicable
• Verify expedited reporting timelines met

6.3 Participant Protection

• Assess child-friendly environment
• Review child abuse reporting procedures
• Verify staff training on child protection
• Check privacy protections for minors
• Review parental permission documentation

6.4 Age-Appropriate Procedures

• Verify procedures modified for pediatric population
• Check age-specific normal ranges used
• Review accommodation for family participation
• Assess minimization of participant burden

7. Related Documents

• FRM-006 Audit Checklist
• FRM-007 Audit Report Template
• SOP-002 CAPA
• SOP-PED-001 Pediatric Assent Process
• SOP-SAF-001 Pediatric Safety Monitoring

8. References

• ICH-GCP E6(R2) Section 5.19 (Monitoring and Auditing)
• 45 CFR 46.103 (Assurance of Compliance)
• 21 CFR 312.56 (Review of Ongoing Investigations)
• ISO 19011:2018 (Guidelines for Auditing Management Systems)

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Revision History

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