Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling
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 associated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic p...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/3/328 |
| _version_ | 1827305330212601856 |
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| author | André Bitterlich Andrej Mihorko Michael Juhnke |
| author_facet | André Bitterlich Andrej Mihorko Michael Juhnke |
| author_sort | André Bitterlich |
| collection | DOAJ |
| description | 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 associated 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 operational 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. |
| first_indexed | 2024-04-24T17:55:21Z |
| format | Article |
| id | doaj.art-b3771e0a586942acbf66e7a5d8aad1d2 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-24T17:55:21Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b3771e0a586942acbf66e7a5d8aad1d22024-03-27T13:59:37ZengMDPI AGPharmaceutics1999-49232024-02-0116332810.3390/pharmaceutics16030328Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process ModelingAndré Bitterlich0Andrej Mihorko1Michael Juhnke2Novartis Pharma AG, Fabrikstrasse 2, 4056 Basel, SwitzerlandNovartis Pharmaceutical Manufacturing LLC, Verovškova Uulica 57, 1000 Ljubljana, SloveniaF. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, SwitzerlandWet 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 associated 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 operational 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.https://www.mdpi.com/1999-4923/16/3/328design spacecontrol strategyquality-by-designrisk assessmentmechanisticmodeling |
| spellingShingle | André Bitterlich Andrej Mihorko Michael Juhnke Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling Pharmaceutics design space control strategy quality-by-design risk assessment mechanistic modeling |
| title | Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling |
| title_full | Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling |
| title_fullStr | Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling |
| title_full_unstemmed | Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling |
| title_short | Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling |
| title_sort | design space and control strategy for the manufacturing of wet media milled drug nanocrystal suspensions by adopting mechanistic process modeling |
| topic | design space control strategy quality-by-design risk assessment mechanistic modeling |
| url | https://www.mdpi.com/1999-4923/16/3/328 |
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