Process Analytical Technology (PAT) enables real time in-situ process monitoring and control of critical quality attributes (CQAs) to ensure the product quality and safety of active pharmaceutical ingredients (APIs) and drug products (i.e., oral dosage/tablets, injectables). PAT implementation starts during process development and is continuously refined during scale-up to ensure reliable deployment and integration at the manufacturing site.
PAT has been strategically implemented for various in-line process controls for the development of APIs and drug products at CONTINUUS Pharmaceuticals. For example, reaction monitoring by PAT tools, (i.e., Mid-Infrared and Raman spectroscopy) provides indispensable information about initiation, conversion, potential intermediates impurity profile, endpoints of a reaction, solvent composition, and kinetics. This process understanding may otherwise be too costly if not unobtainable with off-line analytical methods. In-line analysis of the crystallization process by focused beam reflectance measurements (FBRM) and Raman can provide the process understanding of particle size distribution, crystal shapes, and crystal form as key attributes for filtration and drying unit operations. Additionally, moisture content and residual solvents, API forms, and particle attrition/agglomeration can be analyzed by Near-Infrared spectroscopy (NIR), infrared (IR), and FBRM, respectfully. Content uniformity of the finished drug product is a critical quality attribute that can be measured by NIR (i.e., for oral drug tablet) and UV/vis (i.e., for injectable drug products (vials)) to perform real time release testing, ensuring the quality of the final drug products. Dissolution profile (UV/vis), blend uniformity (NIR), and crystallinity confirmation (Raman and IR) are also considered as CQAs for in-line analysis of APIs and drug products.
PAT coupled with integrated control system results in a more capable quality control system for real time monitoring and controlling of CQAs in unit operations. At CONTINUUS Pharmaceuticals, PAT tools are systematically deployed for various unit operations after demonstrating feasibility including risk assessment and control strategy development during the process characterization activities with an aim to implement and ensure the quality and safety of API/drug product at Integrated Continuous Manufacturing (ICM) facility.