Metabolomics data and the biomarker qualification process

Abstract

Since its initial applications in healthcare research over a decade ago, metabolomics has matured into a technology that can now reliably detect and quantify hundreds of metabolites in biofluids and tissue samples. With substantial improvements in analytical capabilities in recent years, metabolomics now has the potential to provide sensitive and specific biomarkers of health and disease status, drug toxicity and therapeutic efficacy. Although many of the clinical biomarkers currently in use are metabolites such as glucose, cholesterol, and creatinine, few, if any, new metabolites (or panel of metabolites) derived from metabolomic analyses have been submitted to the FDA as biomarker candidates. Under a recent FDA draft Guidance for Industry from the Center for Drug Evaluation and Research (CDER), biomarkers discovered using metabolomics, like those derived from genetic, transcriptomic, and proteomic studies, may be submitted to CDER for consideration as new drug development tools and entered into a formal biomarker qualification process. The qualification process begins with a letter of intent from the submitter, followed by discussions with FDA and then the submission of data supporting the performance of the biomarker within a specific context of use. CDER forms a Biomarker Qualification Review Team at the start of the interactive process to advise the biomarker developer on the type of information important to support the proposed context of use, and review the data that evaluates the biomarker for the proposed context of use when the biomarker development appears complete and the full supporting data are submitted. Once qualified, a biomarker can be used in drug development within the qualified context of use without requesting additional regulatory review concerning its suitability.