Bitterlich, Andre, Mihorko, Andrej and Juhnke, Michael (2024) Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspension by Adopting Mechanistic Process Modeling. Pharmaceutics, 16 (3). p. 328. ISSN 1999-4923

Abstract

Wet media milling is a fully industrialized technology for the manufacturing of drug-nanocrystal suspensions. This work describes the development of an advanced control strategy and an asso-ciated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic process modeling have been used to establish a physically reasonable control strategy of factors relevant to the quality attributes of the nanocrystal suspension. The design space has been developed based on a mature mechanistic process model of the wet media milling procedure. It presents the process–product attribute relationship between a multidimensional range of measured process parameters and a range of the product-quality attribute mean particle sizes. The control strategy allows for simple, robust, and sound scientific process control as well as the op-erational flexibility of the suspension batch size. This is an industrial case study of control strategy and design-space definition with the crucial contribution of mechanistic process modeling for an intended commercial manufacturing process.

Item Type:	Article
Keywords:	Design space, control strategy, quality-by-design, risk assessment, mechanistic, modeling, wet stirred media milling, nanocrystal, nanosuspension, drug nanoparticles
Date Deposited:	19 Mar 2024 00:45
Last Modified:	19 Mar 2024 00:45
URI:	https://oak.novartis.com/id/eprint/52736