Solutions for Vaccine Testing

Importance of the topic

Vaccines are among the most effective tools in preventing infectious diseases and reducing mortality worldwide. Ensuring their safety, potency and consistency demands robust analytical methods and rigorous data management throughout research, development and production processes. Modern challenges such as emerging pathogens, complex biologics, and stringent regulatory requirements highlight the need for advanced analytical solutions.

Objectives and Overview

This whitepaper from Shimadzu presents a comprehensive suite of analytical strategies tailored to vaccine testing. It covers four key areas:

• Data integrity management to meet regulatory guidelines.
• Real-time monitoring of cell culture supernatants during antigen production.
• Quantitative analysis of active ingredients and adjuvants in final formulations.
• Assessment of process residuals and aggregate profiles to assure safety and efficacy.

Methodologies and Instrumentation

A range of high-performance instruments and software platforms are applied:

• LabSolutions DB/CS for secure data acquisition, audit trails and remote backup.
• UHPLC-MS/MS (LCMS-8050/8060) for profiling 95 metabolites in cell culture media and for saccharide unit quantitation in polysaccharide vaccines.
• MALDI-TOF MS (AXIMA-Performance, MALDI-8020) for rapid subunit mass fingerprinting of protein vaccines.
• ICP-OES (ICPE-9820) and ICP-MS (ICPMS-2030) for precise determination of aluminum adjuvant levels.
• LC-MS/MS assays for residual inactivating agents (sodium deoxycholate) and precipitants (CTAB) in final products.
• Aggregates Sizer (SALD-7500nano) for real-time measurement of subvisible particle size and concentration under stress conditions.

Main Results and Discussion

• Data Integrity – LabSolutions DB/CS enforces strict user management, automated audit trails (instrument, data, user actions) and scheduled backups to satisfy FDA 21 CFR Part 11 and GMP requirements.
• Cell Culture Monitoring – A 17-minute UHPLC-MS/MS method quantified carbohydrates, amino acids, nucleosides and vitamins in supernatants, guiding optimization of feed strategies and medium composition.
• Polysaccharide Vaccine Analysis – A derivatization-free LC-MS/MS assay resolved uronic acids, hexoses, hexosamines and methylpentoses in 23-valent pneumococcal vaccine hydrolysates with high sensitivity (LOD <1 ng/mL), precision (<2% RSD) and accuracy (>97%).
• Protein Subunit Profiling – MALDI-TOF MS enabled direct detection of five viral protein subunits in <10 minutes, confirming correct subunit stoichiometry and integrity in formulated samples.
• Aluminum Adjuvant Quantitation – Both ICP-OES and ICP-MS methods achieved linear calibration (R²≈0.9999), low detection limits (0.90 mg/L and 0.17 mg/L respectively) and 107–116% recovery in Tet-anus and DPT vaccines.
• Residual Surfactant Detection – LC-MS/MS simultaneously measured sodium deoxycholate and CTAB residues down to 1.6 µg/L with minimal carryover and no derivatization, ensuring trace-level impurity control.
• Aggregate Characterization – Aggregates Sizer tracked subvisible particle size and counts under mechanical stirring and temperature stress, revealing particle loss upon mixing and damage from freeze-thaw cycles, critical for maintaining vaccine potency.

Benefits and Practical Applications

These integrated solutions deliver:

• Faster analytical throughput and reduced sample prep.
• Higher detection selectivity and resistance to matrix interference.
• Real-time process control data to accelerate development and scale-up.
• Comprehensive compliance with global pharmaco-peial and regulatory standards.
• Enhanced confidence in product safety, purity and performance.

Future Trends and Possibilities of Use

• Adoption of multi-omics and digital manufacturing for next-generation vaccines.
• Further integration of AI-driven data analytics to predict process deviations.
• Expansion of high-throughput MS workflows to support personalized and mRNA-based immunizations.
• Continued evolution of biopharmaceutical analytics to address emerging viral threats.

Conclusion

A multi-modal analytical approach combining secure data management, high-resolution chromatography, mass spectrometry, elemental analysis and particle sizing provides a robust framework for vaccine quality assurance. Implementation of these advanced methods enables faster, more reliable development, production and regulatory compliance, ultimately contributing to safer, more effective vaccines.