(260d) Process Control Strategy Development for a Challenging Drug Powder Blending Process Via Real-Time Process Analytical Technology (PAT) Monitoring and Prediction

Patel, A., CDER/FDA
Sowrirajan, K., FDA/CDER
Powder blending is one of the key unit operations, for which the performance and outcome of the unit operation could significantly impact the critical quality attributes of oral solid dosage forms such as, assay, content uniformity (CU) or uniformity of unit dose. The significance of powder blending becomes more profound for cohesive drugs and narrow therapeutic index (NTI) drugs. The following three aspects will be covered in this presentation. 1) A laboratory case study with Near-Infrared Spectroscopy (NIRS) real time process monitoring and chemometrics model prediction for a high-shear granulator powder blending process consisting of the NTI drug, Phenytoin Sodium (10% w/w) and two common pharmaceutical excipients. 2) Proper choice of the data-preprocessing algorithms to facilitate scale-up using available publicly available information. 3) Some common practices of mitigating risks to blending uniformity and content uniformity as applied to batch processing and continuous processing. This presentation will demonstrate that from both public health and process engineering perspectives, real time process monitoring, and prediction can play a vital role for understanding, controlling, and risk mitigation of a challenging drug powder blending process.