Integrating sensors for monitoring blend content in a pharmaceutical continuous manufacturing plant.

In a pharmaceutical manufacturing process, Critical Quality Attributes (CQAs) need to be monitored not only for the final product but also for intermediates. Blend uniformity of powders is one such attribute that needs to be measured to ensure the quality of the final product. Multiple in-line sensors were implemented within a Direct Compaction (DC) continuous tablet manufacturing line to monitor the blend content of the powders. In most cases, since the primary ingredient of interest is the active pharmaceutical ingredient (API), the concentration (potency) of the API was monitored/predicted over the course of manufacturing. For the calibration model building process, a unique setup involving dynamic powder spectral acquisition method was used. This setup was aimed at mimicking the powder flow characteristics within the manufacturing line, while at the same time utilizing a relatively small amount of powder. A Raman probe and a portable NIR were used concurrently at the exit of the blending process before the tableting stage. The performance of the two sensors and their respective models were evaluated in terms of accuracy, precision, operating range, measurement frequency, placement, reliability, robustness, and compared to predictions using gravimetric feed rates. Additionally, their performances were validated by off-line traditional analytical measurements.