Establishing Best Practice for the Application and Support of Solubility Purge Factors
Michael J. Burns, Ian X. Andrews, Jens-Christoph Baumann, Eric L. Elliott, Jared W. Fennell, Jeffrey M. Kallemeyn, Sébastien Lemaire, Natasha S. Murphy, Magali Palacio, Steven A. Raw, Alastair J. Roberts, Nayrton Flávio Moura Rocha, Didier Schils, Rolf Schulte Oestrich, Andrew L. Shannon-Little, Neil G. Stevenson, Pere Talavera, Andrew Teasdale, Michael W. Urquhart, Fernanda Waechter
Abstract
The increased usage of purge arguments for demonstrating control of mutagenic impurities in drug substances, in accordance with ICH M7, necessitates an increasingly standardized approach to their implementation across industry. The strength of the approach is highly reliant upon a conservative implementation of the principles to maintain regulatory confidence. Different parameters may influence a purge calculation, such as reactivity, solubility, and volatility. While reactivity data are commonly available in literature, there are comparatively fewer resources to draw upon when assigning purge values for solubility related purifications, despite these processes accounting for high degrees of purge and there being an abundance of different techniques which can be utilized. Herein, the authors seek to outline general principles to be adopted as an industry wide best practice for the application of solubility-based purge factors.