WHO Prequalification Programme for Vaccines and Biological Products: A Complete Overview

The WHO Prequalification Programme (PQP) is a critical mechanism for ensuring the safety, quality, and efficacy of vaccines and biological products intended for use in global immunization programs. These products, due to their complex nature, require rigorous regulatory scrutiny. This guide outlines the complete process for WHO prequalification of vaccines and biologics, detailing dossier requirements, GMP expectations, cold chain compliance, and post-prequalification monitoring.

Scope of WHO PQP for Vaccines and Biologics:

The program includes the evaluation and prequalification of:

• Vaccines (e.g., measles, hepatitis B, rotavirus, COVID-19, polio)
• Blood-derived products (e.g., immunoglobulins)
• Recombinant proteins and monoclonal antibodies
• Toxoid vaccines, inactivated and live attenuated vaccines

Regulatory References:

• WHO TRS 978 & TRS 1004: WHO Guidelines on regulatory assessment of vaccines
• WHO Biologicals Guidelines: Including stability, lot release, and characterization
• WHO TRS 961 & TRS 986: GMP standards for biologics and vaccines

WHO PQP Process for Vaccines and Biologicals:

1. Expression of Interest (EOI)

WHO issues EOIs based on global health needs. Manufacturers intending to submit must already be licensed by a functional National Regulatory Authority (NRA).

2. Dossier Submission

• Product summary file (PSF) or CTD format (Module 1 to 5)
• Details of raw materials, master and working seed lots
• Characterization of cell banks, viral strains, toxoids
• Specifications and control strategy for drug substance and product
• Stability data including real-time, accelerated, and post-reconstitution studies

3. Clinical Evaluation

• Clinical trial data demonstrating immunogenicity and safety
• Comparison with reference vaccines if applicable
• Post-marketing surveillance data for already licensed products

4. GMP Inspection of Manufacturing Facility

WHO inspects all sites involved in bulk production, formulation, filling, and cold chain storage. Inspections cover:

• Virus seed/ cell bank management and traceability
• Process validation and bioreactor control
• Quality Control (QC) of antigen content and residuals
• Cold storage facilities and temperature monitoring systems
• Lot release procedures and retention sample management

Cold Chain Validation Requirements:

• Validated storage conditions across the supply chain
• Temperature monitoring with alarms and backup systems
• Qualification of storage units, transport boxes, and shipping conditions
• Thermal stability studies in line with WHO PQS specifications

Inspection of Laboratory Testing Facilities:

• WHO assesses both in-house and contract labs for GLP compliance
• Focus on sterility, pyrogen, endotoxin, and potency testing
• Review of WHO Reference Standards usage and lot-to-lot consistency

Lot Release and Batch Certification:

• Lot summary protocols and Certificate of Analysis (COA) for each batch
• Independent batch release by National Control Laboratories (NCLs)
• Cross-checking of batch data with product specifications

Post-Prequalification Activities:

• Annual Product Quality Reports (APQR) for WHO review
• Ongoing monitoring of cold chain performance in distribution
• Notification and review of product variations
• Periodic re-inspections and post-marketing surveillance

Common Deficiencies in Vaccine WHO PQ Inspections:

• Uncontrolled working seed lot documentation
• Gaps in cold chain monitoring during product export
• Incomplete analytical method validation
• Use of non-WHO validated reference standards
• Data integrity gaps in electronic QC systems

How to Prepare for WHO PQ of Biologics and Vaccines:

1. Ensure licensure by a functional NRA with GMP accreditation
2. Align dossier with WHO biologicals and TRS guidance
3. Perform a mock GMP and quality audit using WHO TRS 986/961
4. Map cold chain end-to-end from production to delivery
5. Ensure SOPs are harmonized across seed bank, bulk, and fill-finish operations

Role of WHO PQ in Global Health Procurement:

Prequalified vaccines and biologicals are eligible for bulk procurement by UN agencies and global immunization campaigns. They are trusted for their compliance with the highest regulatory standards and serve as benchmarks for national regulators across LMICs.

Conclusion:

The WHO PQP for vaccines and biologicals is a robust, science-driven framework that ensures product quality and global supply security. For manufacturers, achieving prequalification opens access to large-scale public health programs and validates GMP and cold chain excellence. Navigating the process requires precise dossier preparation, deep understanding of biological product regulations, and flawless execution of quality systems—from seed lot to syringe.