Meeting The Mist Regulations: Human Metabolism in Phase I Using Ams And A Tiered Bioanalytical Approach

Abstract

The metabolites in safety testing and ICH-M3 guidance documents emphasize the importance of metabolites when considering safety aspects for new drugs. Both guidances state that relevant metabolites should have safety coverage in humans (although the guidelines have different definitions of relevant metabolites). Not having safety coverage for important metabolites in humans may cause significant delay in the overall pharmaceutical development program. This article discusses the regulatory background regarding safety and metabolites, as well as outlines an integrated strategy taken by one pharmaceutical company, Lundbeck A/S. Lundbeck uses metabolite exposure data from first-in-man studies, obtained using an accelerator MS approach followed by a two-tiered bioanalytical investigation. This enables early availability of key data on this aspect and, overall, represents a powerful risk mitigation strategy.

Financial & competing interests disclosure

G Lappin and M Seymour are employees of Xceleron Ltd, a company offering accelerator MS-enabled metabolites in safety testing studies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.