Objective The primary objective of this study was to establish and validate a practical framework for the transfer of a Sinomenine Hydrochloride sustained-release tablet from a legacy batch process to a pilot-scale Continuous Direct Compression (CDC) manufacturing line, without altering the product's formulation.Significance The successful transfer of existing products to Continuous Manufacturing (CM) without reformulation represents a major industry challenge. In this work, a significant contribution is made through the validation of a data-driven pathway designed to de-risk this transition. A replicable strategy is demonstrated that aligns with Quality by Design principles and ICH Q13 guidelines, through which enhancements in cost-effectiveness and process sustainability for legacy pharmaceutical products can be achieved.Methods An integrated pilot-scale CDC line, operating at 1.9 kg/h, was utilized, comprising high-precision loss-in-weight feeders, a continuous blender, and a rotary tablet press. A Process Analytical Technology (PAT)-enabled control strategy was implemented, featuring a robust Partial Least Squares (PLS) model developed for real-time API quantification via in-line NIR spectroscopy. Process dynamics and material traceability were characterized using Residence Time Distribution (RTD) analysis to establish a state of control.Results Robust stability and control were demonstrated by the CDC process during a 300-minute steady-state run. Through real-time monitoring, API content uniformity was confirmed to be consistently maintained within a tight ± 3% tolerance. Critically, tablets produced via CDC were proven to be equivalent to the reference batch product across all critical quality attributes, including physical properties and functionally identical 24-hour dissolution profiles.Conclusion In this study, a comprehensive framework for the batch-to-continuous transfer of a sustained-release tablet is successfully validated. Process robustness is ensured by the PAT-enabled control strategy, which provides a reliable method for real-time quality verification. Based on the demonstrated product quality equivalence, the approach is confirmed as a low-risk, guideline-compliant pathway for modernizing the manufacturing of existing pharmaceutical products.
Zhou et al. (Tue,) studied this question.