Understanding GMP Requirements for WHO PQP Requalification

Maintaining WHO Prequalification status is as critical as obtaining it. For pharmaceutical manufacturers, requalification under the WHO Prequalification Programme (PQP) is a mandatory process to ensure continued compliance with international GMP standards. WHO’s GMP requalification process involves reassessment of manufacturing sites, documentation, and quality systems. This article provides a comprehensive guide to the GMP requirements and best practices for ensuring seamless requalification under WHO PQP.

What Is WHO PQP Requalification?

WHO prequalification is valid for a defined period—typically 3 to 5 years depending on the product type and risk category. Requalification involves WHO re-inspecting the facility and reviewing updated dossiers and GMP documentation to confirm that compliance has been maintained since the initial approval.

Triggers for WHO Requalification:

• Time-bound expiry of WHO prequalification status
• Significant post-approval changes (e.g., formulation, facility, process)
• New product line extensions under the same facility
• WHO surveillance mechanisms or procurement partner requests

WHO’s Risk-Based Approach to Requalification:

Not all products or sites are requalified at the same frequency. WHO uses a risk-based model considering:

• Product type (e.g., sterile, biologicals = higher risk)
• Previous inspection findings and CAPA effectiveness
• Procurement volume and market criticality
• Post-market quality surveillance results

GMP Requirements for WHO PQP Requalification:

1. Updated Site Master File (SMF)

• Clearly reflect any structural or operational changes
• Incorporate updated personnel organograms and equipment inventories
• Align with WHO TRS 961 Annex 14 recommendations

2. Current GMP Certificates and Licenses

• GMP certificate from the National Regulatory Authority (NRA)
• Valid manufacturing and import/export licenses

3. Documented Changes Since Initial PQ

• Chronology of all variations filed with WHO and respective approvals
• Summary of post-approval changes to SOPs, process controls, and QC methods
• Product shelf-life extensions or formulation tweaks supported by stability data

4. CAPA and Quality System Updates

• Follow-up status of previous WHO inspection findings
• CAPA implementation logs and internal audit summaries
• Training records for GMP updates and procedural changes

5. Facility Readiness for Reinspection

• Production area walkthroughs should demonstrate compliance and consistency
• QC labs must maintain audit trail and data integrity logs
• Storage and stability chambers should be fully qualified and monitored

WHO Requalification Inspection Scope:

The inspection includes a comprehensive review of:

• Documentation and version control systems
• Change control and deviation trend analysis
• Training matrix for QA, QC, and production teams
• Batch record traceability and review of executed BMRs
• Environmental monitoring and HVAC maintenance logs

Critical Focus Areas for Requalification:

• Data integrity and compliance with ALCOA+ principles
• Qualification of any new equipment or production lines
• Cleaning validation updates, especially in shared facilities
• Out-of-trend (OOT) and out-of-specification (OOS) handling and CAPA
• Updated SOPs for GMP documentation, deviation control, and audit readiness

Stability Testing and Shelf-Life Justification:

• Long-term stability data for batches manufactured post-initial PQ
• Validation of stability indicating methods
• Storage condition requalification data (e.g., Zone IVb for tropical markets)
• In-use stability data for multi-dose or reconstituted formulations

Common Gaps Observed During Requalification:

• Failure to document or report variations to WHO
• Inconsistencies between SOPs and actual practices
• Expired validation studies or unverified cleaning procedures
• Deficient internal audit programs and CAPA follow-up

Tips for a Smooth WHO PQP Requalification:

1. Start preparation 9–12 months before PQ expiration
2. Conduct a gap analysis using WHO TRS 986 and 961 references
3. Update all critical GMP documents and SOPs with version control
4. Re-train staff on new procedures or changes post-initial PQ
5. Maintain a centralized requalification readiness checklist and timeline

Post-Requalification Activities:

• Submission of additional documents if requested (e.g., training logs, audit trail reports)
• Ongoing monitoring of GMP compliance through self-inspection programs
• Tracking variations and reporting them through WHO’s e-submission platform
• Responding to WHO queries or minor observations within designated timelines

Conclusion:

WHO PQP requalification is a rigorous but rewarding process that reinforces GMP credibility and global access eligibility. With a structured requalification strategy—spanning document updates, site readiness, CAPA tracking, and procedural alignment—manufacturers can maintain WHO status confidently. Sustained GMP compliance is not a one-time milestone but a continuous journey, and WHO requalification ensures that this journey is both globally validated and supply chain resilient.