Stability of live plague vaccine production: Analysis of potency using Shewhart charts

INTRODUCTION. Monitoring the stability of live plague vaccine production is critical for releasing an effective and safe medicinal product. Shewhart control charts represent a promising tool for this task, enabling statistical assessment of process stability based on the key quality attribute — potency (number of live microbial cells). AIM. This study aimed to evaluate the stability of live plague vaccine production through a retrospective analysis of potency (number of live microbial cells) of batches using Shewhart control charts (X and R charts) and correlation analysis. MATERIALS AND METHODS. A retrospective analysis of quality control results for the attribute Potency was performed on 121 batches of live plague vaccine manufactured in the Russian Federation from 2012 to 2025. Potency was assessed as the number of live microbial cells (percentage of the total cell count). Statistical process stability was evaluated using the Shewhart control chart method. Two types of charts were constructed: moving range charts (R charts) to assess homogeneity, and individual value charts (X charts) to assess process stability. Data from the manufacturer’s summary protocols and results obtained at the Testing Center were used. The Pearson correlation coefficient ( r ) was calculated. RESULTS. Analysis of control charts for the period 2012–2018 revealed signs of statistical instability of the manufacturing process: both X and R charts exhibited points and trends outside the control limits (special cause criteria), indicating an uncontrolled process state and requiring corrective actions. Data from 2019–2025, obtained after manufacturing process optimization, showed stabilization of the indicators: the number of special cause criteria decreased, and the duration of in-control periods increased. Correlation analysis revealed a strong positive relationship ( r =0.7) between the manufacturer’s results and those of the Testing Center. CONCLUSIONS. Shewhart control charts are an effective tool for statistical process control in pharmaceutical manufacturing. Their application to assess the stability of live plague vaccine production demonstrated that modernization of the manufacturing process facilitated a transition from a statistically unstable state to a controlled state. The high correlation between the manufacturer’s and the Testing Center’s results ( r =0.7) confirms the reliability of the quality control system. Therefore, the Shewhart chart method can be recommended for monitoring the manufacturing stability of vaccine products.