Application of Laser Particle Size Analyzer to Evaluation of Batch Consistency and Stability of Aluminum Adjuvant Adsorbed Vaccine

Background/Objectives: Aluminum-adjuvanted vaccines are widely used in pediatric immunization, yet particle size and distribution are critical but under-standardized quality attributes. Methods: This study aimed to establish and validate a laser diffraction particle size analysis for evaluating particle size consistency and stability of inactivated enterovirus 71 (EV71) vaccine and adsorbed acellular diphtheria–tetanus–pertussis (DTaP) vaccine. Results: EV71 vaccine stock solution (40–350 nm) and aluminum adjuvant (75–600 nm) exhibited distinct distributions, with the final product showing bimodal distribution (50–14,000 nm): main peak at 0.1–0.2 μm (~65%) and secondary peak at 0.3–3 μm (~14%). DTaP final product (2000–20,000 nm) showed significant aggregation with 79.6% at 3–8 μm and 15.7% at >8 μm. Four EV71 batches (A1–A4) showed uneven inter-batch consistency (D50: 100, 132, 103, 103 nm; CV 13.8%), while intra-batch CVs were acceptable (3.9% for EV71, 8.0% for DTaP). Long-term stability at 4°C revealed gradual aggregation: EV71 D50 increased from 100 nm to 134 nm over 60 days, with >0.2 μm aggregates increasing from 0.03% to 1.50%; DTaP showed severe tailing at day 60 (>50 μm particles: 2.8%). Accelerated studies showed 37°C caused slight enlargement, whereas −20°C induced marked aggregation (EV71 D50: ~37 μm, CV 16.1%; DTaP D50: ~45 μm, CV 13.8%). Conclusions: Laser particle size analysis is a robust, reliable tool for assessing particle size consistency and stability of aluminum-adjuvanted vaccines. It supports process control, batch release, and stability monitoring to improve vaccine quality and safety.