Continuous OSD

Overview

Continuous manufacturing is an alternative to batch processing, where starting materials are constantly fed and transformed and end materials are constantly removed. Continuous manufacturing has advantages of reduced operational footprint, manufacturing flexibility, and enables implementation of robust testing and controls. Continuous manufacturing was supported in the 2004 FDA guidance paper on innovation in pharmaceutical manufacturing, but it was not widely considered as practical until the FDA made its first continuous process approval in 2015. A 2021 review of continuous manufacturing highlighted the 7 product approvals that involved continuous manufacturing between 2015-2018.  In one example, Janssen revealed that they were able to reduce the number of rooms from 7 to 2 and the time to a complete product from 2 weeks to 1 day when they adopted a continuous manufacturing approach for Prezista 600 mg tablets. The Prezista process integrated feeding and weighing, granulation, blending, compression, and film coating into a single line. The speed and scale of continuous operations underscores the importance of high equipment uptime, data storage and analysis, and the reliance on a robust control strategy.

Ideally, the control strategy for continuous oral solids manufacturing uses performance-based measurements that provide continuous measurements of critical quality attributes, and allows for feed-forward or feedback adjustment of process parameters. For this reason, spectroscopic PAT is critical to development of performance-based control strategy for continuous manufacturing. Development of performance-based control strategy begins in late development, often using scale-down versions of commercial equipment to quickly build process knowledge and identify the optimal control strategy using minimal API. Because the process development occurs in tandem with analytical development, an ideal approach would use scale-down equipment that can allows multiple analyses to quickly gain process knowledge. A 2025 conference presentation by Di Giorgi demonstrated the use of Expo’s FFSim™feed frame simulator to optimize continuous direct compaction process and the inline NIR measurements for formulation quality.

Similar to batch operations, blend uniformity and particle size distribution are critical quality attributes in continuous solids manufacturing. Blend uniformity is typically measured at multiple points in a continuous solids manufacturing; some common sites of blend uniformity measurements are: after blending, during granulation, and before compaction. Particle (or granule) size distribution is measured in wet or dry granulation or in roller compaction following dry granulation. The decreased processing time and integration of multiple unit operations into a continuous operation places new demands on the processing and measurement equipment. And a successful analytical strategy for continuous solids measurements needs to not only consider the measurement capabilities but also how the solid material is handled. The “process-to-PAT” interfaces provided by Expo Process Analytics are critical in continuous solids manufacturing to provide a consistent sample presentation and a defined probe window cleanliness whether the solid stream is dense or disperse.