FDA MIST Guidance

Xceleron’s Solution to the FDA MIST Guidance

Gain a first view of human metabolites and an early safety assessment for your drug candidate using our Solution to MIST Service. Our ultra-sensitive analytical approach goes far further than LC-MS/MS to deliver clear and quantitative assessments of significant or disproportionate metabolites very early in phase I.

Our data has enabled clinical researchers worldwide to compare human metabolite profiles with those obtained from preclinical in vitro and in vivo studies, in accordance with the FDA MIST and ICH M3 guidances.

As well as using this data to satisfy regulatory guidances, you can design the study to obtain further information including extent of metabolism, and routes and rates of excretion.

Xceleron’s ¹⁴C Microtracer Approach

We incorporate a ¹⁴C microtracer into an existing Phase I SAD, MAD or Food Effect study. We combine the clinical plasma samples to form a single AUC pool across all subjects at all time points and analyze this pool to give a single metabolite profile.

By adding to an existing early clinical study, we ensure that this vital early metabolism insight comes at small incremental cost.

Due to the small amounts of radiotracer used, these studies are classified non-radioactive so no dosimetry or associated regulatory submissions are required.

FDA ‘Safety Testing of Drug Metabolites’ (MIST) guidance

The MIST guidance focuses on the need to determine if human metabolites are being adequately evaluated during non-clinical safety studies. Problems may occur when a metabolite is human-specific, or, more commonly, when a metabolite is present in disproportionately higher levels in humans than in the animal species used.

The guidance states “Human metabolites that can raise a safety concern are those formed at greater than 10% of parent drug systemic exposure ….” (1). FDA provides guidance on timing – “Human in vivo metabolism studies usually have been performed relatively late in Drug Development, but we strongly recommend in vivo metabolic evaluation in humans be performed as early as possible” *.

Xceleron’s Solution to MIST Service has delivered detailed human metabolite data for GSK’s VERAMYST®.

* FDA Guidance For Industry – Safety Testing of Drug Metabolites (2008)