Pauli, Victoria Isabell, Elbaz, Frantz, Kleinebudde, Peter and Krumme, Markus (2018) Methodology for a variable rate Control Strategy development in Continuous Manufacturing applied to twin-screw wet-granulation and continuous fluid-bed drying. Journal of Pharmaceutical Innovation.

Abstract

It is demonstrated how science-based control strategy development in continuous manufacturing (CM) of solid oral dosage forms can be facilitated through a systematic step-by-step approach. General guidelines on manufacturing control strategy development as well as numerous examples for the application of such to pharmaceutical batch processes can be found in literature. However, only little experience on systematic development of drug products by CM is available up to this date, since the majority of pharmaceutical companies are still hesitant to adapt CM as the new production standard. It is demonstrated, how comprehensive understanding of CM-process behavior can be established through methodical risk assessment and subsequent Design-of-Experiment-testing of factor-response relationships. Diclofenac-Sodium is used as a drug substance. To reduce the complexity, the demonstration is limited to the process-units twin-screw wet-granulation and continuous fluid-bed drying. Critical process parameters and critical material attributes in regard to the dried granules’ critical quality attributes moisture content and particle size distribution were identified and quantified. The gained process knowledge was then implemented in real-time, model-based compensatory control actions that can ensure the final product has consistent, uniform character and quality within specified limits at all times, despite certain process variations. Although the quantitative findings of this study are distinctively related to the investigated substance and process, the demonstrated methods can be applied to other CM-processes and intend to simplify future CM-development procedures. The current models are limited to quasi-static processes, meaning that the process time constants are slower than the equipment related time constants that influence the process state.

Item Type:	Article
Date Deposited:	16 May 2018 00:45
Last Modified:	16 May 2018 00:45
URI:	https://oak.novartis.com/id/eprint/34335