Looking Back Through the MIST: A Perspective of Evolving Strategies and Key Focus Areas for Metabolite Safety Analysis

Abstract

The publication of the US FDA MIST guidance document in 2008 reignited the debate around the most appropriate strategies to underwrite metabolite safety for novel compounds. Whilst some organizations have suggested that the guidelines necessitate a paradigm shift to more thorough metabolite analysis during early development, an evaluation of historical practices shows that the principles of the guidelines have always largely underpinned metabolism studies within the pharmaceutical industry. Therefore, it is argued that existing practices, when coupled to appropriate emerging analytical tools and a case-by-case consideration of the relevance of the generated metabolism data in terms of structure, physicochemisty, abundance and activity, represent a fit-for-purpose approach to metabolite-safety assessments.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organizations or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.