Aluminum Phosphate Vaccine Adjuvant: Analysis of Composition and Size Using Off-Line and In-Line Tools

Area of Science:

• Pharmaceutical Manufacturing
• Materials Science
• Analytical Chemistry

Background:

• Aluminum phosphate (AlPO4) is a key adjuvant in human vaccines, enhancing immune response.
• Physicochemical properties like particle size and composition are crucial for AlPO4 adjuvant immunogenicity and vaccine quality.
• Monitoring these attributes throughout manufacturing ensures product consistency and efficacy.

Purpose of the Study:

• To evaluate the use of in-line and off-line analytical methods for monitoring AlPO4 adjuvant manufacturing.
• To assess the physicochemical properties (particle size, chemical composition) of AlPO4 at different production stages.
• To demonstrate the application of Process Analytical Technology (PAT) for real-time quality control.

Main Methods:

• Off-line analysis: Fourier-Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, X-ray Photoelectron Spectroscopy (XPS), Laser Diffraction (LD).
• In-line analysis: Attenuated Total Reflectance (ATR) spectroscopy, Focused Beam Reflectance Measurement (FBRM®), ReactIR probe.
• Monitoring of AlPO4 adjuvant and model antigen (Tetanus toxoid) adsorption.

Main Results:

• No significant differences in AlPO4 particle size distribution were observed between intermediate and final stages using both in-line and off-line methods.
• Consistent spectral shifts in IR and XPS indicated stable chemical composition during manufacturing.
• In-line IR spectroscopy and FBRM® successfully monitored reaction progress and particle size in real-time.

Conclusions:

• In-line PAT effectively monitors AlPO4 adjuvant particle size and chemical composition throughout the manufacturing process.
• These methods can ensure lot-to-lot consistency in adjuvant manufacturing and vaccine development.
• In-line PAT supports advanced manufacturing strategies like real-time release testing and automation.