Comparing PIC/S and WHO GMP Inspection Models

Good Manufacturing Practice (GMP) inspections are fundamental to ensuring the safety, efficacy, and quality of pharmaceutical products. Two of the most influential global frameworks for GMP compliance are the Pharmaceutical Inspection Co-operation Scheme (PIC/S) and the World Health Organization (WHO) Prequalification Programme (PQP). Although they share similar goals, their operational models differ in structure, regulatory scope, and implementation. This article presents an expert comparison of PIC/S and WHO GMP inspection models, helping pharmaceutical professionals navigate global compliance expectations.

Overview of PIC/S and WHO GMP Frameworks

• PIC/S: A voluntary cooperation of over 50 pharmaceutical inspectorates promoting GMP harmonization, training, and mutual recognition
• WHO PQP: A global initiative that inspects pharmaceutical manufacturers, primarily for public health procurement in low- and middle-income countries (LMICs)
• Both use internationally accepted GMP standards and aim to ensure product quality and supply chain integrity

Regulatory Scope and Membership

• PIC/S:
  • Membership is limited to national competent authorities
  • Emphasizes harmonization among member states and mutual inspection reliance
  • Members include US FDA, EMA agencies, Health Canada, TGA, Swissmedic, and others
• WHO PQP:
  • Focuses on prequalification of medicines for public sector procurement
  • Performs inspections globally, especially in LMICs
  • Works with manufacturers, donor agencies, and UN procurement bodies

GMP Guidelines Used

• PIC/S:
  • Follows GMP standards aligned with EudraLex Volume 4 (EU GMP)
  • Incorporates WHO guidelines and ICH Q7–Q12 where applicable
  • Emphasizes uniformity in interpretation across inspectorates
• WHO:
  • Uses WHO Technical Report Series (TRS) 986, 1010, and 1025
  • More adaptable to various infrastructure levels in LMICs
  • Also references ICH and regional guidelines to assess compliance

Inspection Focus and Approach

• PIC/S:
  • Risk-based inspection planning for pre-approval and routine surveillance
  • Standardized use of aide-memoires and deficiency classification (critical, major, other)
  • High emphasis on systems-based audits (QMS, documentation, validation, data integrity)
• WHO:
  • Focuses on critical areas relevant to product safety, especially for essential medicines
  • Evaluates readiness for WHO prequalification and donor procurement eligibility
  • Includes broader public health considerations, such as cold chain and stability monitoring

Inspection Procedure Differences

• PIC/S:
  • Conducted by national regulatory inspectors following standard GMP enforcement mandates
  • Often part of larger mutual recognition and regional cooperation frameworks
  • Used for both human and veterinary medicinal products
• WHO:
  • WHO inspectors or contracted experts visit sites for PQP review
  • Site inspection is part of a broader dossier assessment and quality system evaluation
  • Applicable to both finished product and active pharmaceutical ingredient (API) manufacturers

Inspection Tools and Templates

• PIC/S:
  • Harmonized inspection templates and report formats
  • Aide-memoires for specific GMP areas (e.g., sterile manufacturing, ATMPs)
  • CAPA follow-up tools and post-inspection review templates
• WHO:
  • Checklists specific to WHO GMP for PQP inspections
  • Detailed report structures outlining deficiencies and timelines for correction
  • Risk-ranking based on product classification (life-saving vs. non-critical)

Training and Inspector Qualification

• PIC/S:
  • Provides structured training programs, workshops, and e-learning modules
  • Member states conduct inspector mentoring and performance evaluation
• WHO:
  • Trains internal staff and contracted experts for inspections
  • Works closely with regional regulatory networks to build inspection capacity in LMICs

Reporting and Follow-Up

• PIC/S:
  • Findings are communicated via formal deficiency letters
  • Reports may be shared within PIC/S members for reliance purposes
  • Non-compliance statements posted on EudraGMDP or national websites
• WHO:
  • Reports are used internally to decide on PQP listing
  • CAPA responses required from manufacturers with timelines
  • May trigger reinspection or rejection of prequalification

Strengths of Each Model

• PIC/S:
  • Widely accepted by high-income country regulators
  • Focuses on systemic GMP inspection quality and mutual recognition
  • Supports long-term harmonization and convergence goals
• WHO:
  • Designed for global public health and access to quality-assured medicines
  • Flexible and adaptable to site maturity and resource limitations
  • Incorporates supply chain and donor accountability concerns

How They Work Together

• PIC/S and WHO frequently collaborate on training, guideline development, and joint inspections
• WHO often references PIC/S templates and inspection frameworks
• Both contribute to global initiatives like ICH and regional harmonization programs

Conclusion

While PIC/S and WHO GMP inspection models serve different strategic goals, their alignment plays a critical role in shaping the global regulatory landscape. PIC/S offers a harmonized, peer-recognized approach among advanced regulators, whereas WHO brings adaptability and access-focused oversight for essential public health products. For pharmaceutical companies and regulators, understanding the nuances of both models is essential to ensuring worldwide compliance, streamlined audits, and access to diverse markets.