Evaluation of in-line particle measurement with an SFT-probe as monitoring tool for process automation using a new time-based buffer approach

Abstract

The Process Analytical Technology (PAT) initiative published by the Food and Drug administration (FDA) describes PAT systems as important tools to optimize pharmaceutical processes in order to ensure the final product quality. Real-time particle size measurements provide a promising approach for process automation of fluid bed granulation processes. This work focuses on the introduction and evaluation of a new time-based buffer approach for in-line spatial filtering technique (SFT) in order to provide a minimum time delay of the real-time measurement. Comparing the new buffer system to the conventionally used number-based approach, a reduced influence of the particle rate and a constant response time was found. A performance qualification of the Parsum probe IPP 80 using this buffer approach according to the ICH guideline Q2 was performed to investigate whether common variations of process parameters influence the real-time particle size measurement. Focussing on the main requirements for process control, hereby a good precision and specificity as well as an adequate robustness was found. Summarized, this study identified the time-based buffer system as more suitable buffer system for process automation.