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A New Semi-Automated Computer-Based System for Assessing the Purge of Mutagenic Impurities

Burns, Michael and Ott, Martin and Teasdale, Andrew and Stalford, Susanne and Antonucci, Vincent and Baumann, Jens-Christoph and Brown, Roland and Covey-Crump, Elisabeth and Elder, David and Elliott, Eric and Fennell, Jarred and Gallou, Fabrice and Ide, Nathan and Itoh, Tetsuji and Jordine, Guido and Kallemeyn, Jeffrey and Lauwers, Dick and Looker, Adam and Lovelle, Lucie and Molzahn, Robert and Schills, Didier and Schulte Oestrich, Rolf and Sluggett, Gregory and Stevenson, Neil and Talavera, Pere and Urquhart, Michael and Varie, David and Welch, Dennie (2019) A New Semi-Automated Computer-Based System for Assessing the Purge of Mutagenic Impurities. Organic process research & development.

Abstract

The ICH M7 guidance provides a series of flexible control options for the control of potentially mutagenic impurities (PMIs) that fully align with key risk-based principles. This includes Option 4, which leverages existing process knowledge and/or data to justify control of PMIs without the need for routine analytical release testing during manufacturing. One such tech-nique highlighted uses systematic, semi-quantitative calculations to define the degree of “purge” of PMIs within a synthetic route to an API based on physicochemical properties of the impurities in question, and the manufacturing process being undertaken. This paper introduces a consortium-led initiative which aims to build on the semi-quantitative purge approach, and harmonise industry best practices by enabling the calculations to be conducted in a standardised, consistent and repro-ducible manner. The development of an expert-derived knowledge base for the prediction of reactivity by enhancing expert opinion using evidence derived from published literature and experimental data is also discussed. Furthermore, this paper describes the application of the Mirabilis software for the processes involved in the synthesis of Verbecestat, Naloxegol oxa-late and Camicinal.

Item Type: Article
Date Deposited: 18 Oct 2019 00:45
Last Modified: 18 Oct 2019 00:45
URI: https://oak.novartis.com/id/eprint/40391

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