WHO Inspection Follow-Up: Managing CAPA and Ensuring GMP Compliance

The conclusion of a WHO GMP inspection does not mark the end of the evaluation process—it signals the beginning of a critical compliance phase. Pharmaceutical manufacturers must respond to observations through structured Corrective and Preventive Action (CAPA) plans and undergo continued compliance monitoring. This article explores the WHO inspection follow-up process in detail, outlining CAPA submission expectations, common challenges, and strategies to ensure inspection closure and ongoing GMP adherence.

Post-Inspection Timeline and Milestones:

• Day 0: WHO concludes the on-site inspection and issues preliminary observations
• Day 30: Manufacturer receives the official inspection report
• Day 60: Manufacturer must submit CAPA responses for all observations
• Day 90–180: WHO reviews the CAPA and may request clarifications or supporting documentation
• Post-180: Decision made on GMP compliance status or reinspection requirement

Structure of a WHO Inspection Report:

Inspection reports include:

• Observation number and classification (Critical, Major, Other)
• Description of the GMP deficiency with reference to WHO TRS 986/961
• Supporting evidence and impacted systems or product types
• Recommendations for remediation

Developing a CAPA Plan for WHO Submission:

Each observation must be addressed with a complete CAPA package including:

• Root Cause Analysis (RCA) using tools like 5-Why or Fishbone
• Immediate corrective action steps
• Preventive measures to avoid recurrence
• Timeline and responsible departments
• Effectiveness verification criteria and timelines

CAPA Best Practices:

1. Do not generalize—tailor each CAPA to the specific system and observation
2. Link actions to impacted SOPs, records, and training programs
3. Include measurable targets (e.g., SOP revision dates, retraining schedules)
4. Provide documentary evidence such as revised documents, training records, and validation reports
5. Submit responses in a tabulated format matching WHO’s observation numbering

WHO’s CAPA Review Process:

CAPAs are assessed for completeness, relevance, and traceability. WHO evaluators may:

• Request additional documentation (e.g., raw data, audit trails, retraining logs)
• Conduct virtual clarification meetings
• Delay prequalification until CAPAs are deemed adequate
• Schedule a targeted follow-up inspection if systemic issues persist

Key Focus Areas for WHO Compliance Monitoring:

• Effectiveness of implemented CAPAs
• Evidence of sustained procedural change
• Updates to quality systems (e.g., QMS, change control, document management)
• Training records and employee competency post-inspection
• Performance metrics like deviation frequency, CAPA closure timelines, and audit findings

Role of Stability Testing in Post-Inspection Compliance:

During follow-up, WHO may request updated stability study data if:

• The original study was flagged for protocol or data integrity issues
• Product formulation or packaging was modified post-inspection
• CAPAs impacted storage, shelf-life, or environmental control systems

Manufacturer Responsibilities During Monitoring Phase:

• Track all actions in a CAPA implementation log
• Conduct effectiveness checks (e.g., QA spot audits, retraining assessments)
• Notify WHO of significant delays or issues in implementing actions
• Maintain readiness for a follow-up inspection or virtual review

Common CAPA Pitfalls and How to Avoid Them:

• Vague or superficial root cause analysis: Use structured RCA tools
• CAPAs limited to documentation updates: Include system-level changes and personnel training
• Failure to submit evidence: Attach proof of implementation (scanned SOPs, training logs, etc.)
• Unrealistic timelines: Set achievable milestones with QA oversight

Long-Term Compliance Monitoring:

Post-approval, WHO may request periodic updates or trigger a reinspection based on:

• High volume procurement or critical public health role
• Complaints, adverse events, or recalls reported by procurers
• Observed trends in quality metrics
• Delays in post-approval variation implementation

How WHO Ensures CAPA Sustainability:

• Compares internal audit findings with submitted CAPAs
• Reviews change control records for systemic updates
• Analyzes quality indicators like batch rejection rate or audit trail activity
• Cross-verifies CAPAs during routine requalification inspections

Conclusion:

The follow-up phase of WHO GMP inspections is a critical test of a manufacturer’s commitment to continuous improvement. A well-documented and effectively implemented CAPA plan can not only close observations but elevate overall quality maturity. For sustained WHO prequalification and long-term market access, proactive compliance monitoring, transparent communication, and a robust quality system are essential. Aligning internal QA processes with WHO’s expectations ensures ongoing regulatory confidence and uninterrupted participation in global health supply chains.