A Step-by-Step Guide to WHO GMP Site Inspections

For pharmaceutical manufacturers seeking global market access through the WHO Prequalification Programme (PQP), understanding the steps involved in WHO GMP site inspections is critical. These inspections assess whether a manufacturing facility complies with the World Health Organization‘s GMP standards and determines eligibility for listing on the WHO prequalified product database. This article provides a detailed walkthrough of the inspection process, expectations, and best practices at each stage.

Why WHO GMP Site Inspections Matter:

• Ensure consistent manufacturing quality for global public health use
• Enable procurement by international donors like UNICEF, Global Fund, GAVI
• Allow national regulatory reliance via WHO Collaborative Registration Procedure (CRP)
• Support inspection recognition across more than 100 countries

Step 1: Inspection Planning and Notification

After a product passes initial dossier screening, the WHO PQT team identifies the manufacturer’s site for GMP inspection. An inspection plan is shared, typically 4–6 weeks in advance, detailing:

• Inspection dates and duration (usually 3–5 days)
• Team composition and lead inspector name
• Primary product(s) and dosage form to be audited
• Required documentation and facility access expectations

Step 2: Document Submission and Review

Manufacturers must provide the following before the inspection:

• Site Master File (SMF)
• Validation Master Plan (VMP)
• Batch Manufacturing Records (BMRs)
• Recent internal audit summaries
• Process flowcharts and organograms

Inspectors review these to design a site-specific inspection checklist using WHO TRS 986 and 961 standards.

Step 3: Opening Meeting and Briefing

The inspection begins with an official opening meeting led by the WHO team. This includes:

• Introduction of inspectors and company leadership
• Review of inspection scope and methodology
• Confirmation of communication protocol during the inspection
• Sharing of any initial concerns or focal points

Step 4: Facility Tour and System Mapping

Inspectors conduct a walkthrough of manufacturing, QC, and warehouse areas. They evaluate:

• Personnel gowning and hygiene practices
• Material flow and cross-contamination controls
• Equipment qualification and calibration tags
• HVAC zoning and cleanroom classification

Inspectors also verify the accuracy of floor plans and logical consistency of stated processes.

Step 5: In-Depth Document and Batch Record Review

This is the heart of the inspection. Inspectors select batches for review and trace their complete production history through:

• Master and executed batch records
• Raw material COAs and supplier qualifications
• Environmental monitoring logs
• Deviation records and CAPA closure reports

Good documentation practices (GDP) are closely assessed for compliance with WHO standards.

Step 6: Interviews and SME Discussions

Inspectors engage with subject matter experts (SMEs) from QA, QC, Production, and Engineering departments. Questions focus on:

• Real-time process understanding and SOP adherence
• Deviation management logic
• Batch disposition decision-making
• Knowledge of site-specific risk assessments

Step 7: Stability testing Compliance Check

This includes thorough review of:

• ICH Q1A(R2)-aligned protocols
• Storage condition monitoring logs
• Trend data on degradation pathways
• OOS/OOT handling in real-time and accelerated studies

Inspectors may also cross-check label claims with actual stability data submissions.

Step 8: Observation Classification and Drafting

At the end of each day, inspectors meet internally to categorize observations as:

• Critical: Patient safety risks or severe GMP violations
• Major: Significant impact on product quality but manageable through CAPA
• Other: Minor procedural or documentation issues

Only validated findings are included in the draft list shared during the closing meeting.

Step 9: Closing Meeting and Preliminary Feedback

The inspection concludes with a formal meeting where inspectors:

• Summarize all findings and evidence collected
• Clarify potential misinterpretations
• Explain expectations for CAPA development
• Provide tentative timelines for next steps

Step 10: Final Inspection Report and CAPA Submission

Within 30 days, WHO issues a detailed report listing:

• Each observation, its classification, and reference to WHO GMP clauses
• Evidence and documents reviewed
• Inspector comments on systemic issues

The manufacturer must submit a corrective and preventive action (CAPA) plan, typically within 30 days. The CAPA must include:

• Root cause analysis for each observation
• Specific and measurable corrective steps
• Timeline for implementation
• Verification and effectiveness checks

Step 11: WHO Review and Prequalification Outcome

Based on the CAPA adequacy, WHO may:

• Accept the inspection and grant PQ status
• Request further CAPA refinement or evidence
• Defer prequalification pending a re-inspection
• Reject the application if major risks remain unresolved

Best Practices for Manufacturers:

1. Conduct mock audits using WHO TRS 986 Annex 2 structure
2. Train SMEs for real-time interviews using simulation exercises
3. Ensure SOPs reflect actual practices and are version controlled
4. Maintain an audit room and document control system in readiness
5. Have SOPs on CAPA management specific to WHO expectations

Conclusion:

WHO GMP inspections are structured, evidence-based evaluations of a manufacturing facility’s ability to consistently produce quality-assured medicines. Understanding each inspection step—from planning and SME interviews to post-audit CAPA—is essential for success. By aligning systems, people, and documentation with WHO’s expectations, pharmaceutical companies can not only achieve prequalification but also strengthen their overall GMP maturity and global credibility.