Bioanalytical Method Validation and Study Sample Analysis
ICH M10 harmonises expectations for the validation of bioanalytical methods and the analysis of study samples supporting regulatory submissions. It covers both chromatographic (e.g. LC-MS) and ligand-binding assays, defining validation parameters — selectivity, calibration, accuracy, precision, matrix effect, carry-over, dilution integrity, and stability — plus acceptance criteria for study sample analysis and incurred sample reanalysis (ISR).
What this does not cover
stated in the document's own scope- Does not cover biomarker assays outside its stated scope in the same prescriptive detail
- Does not set the clinical or nonclinical study design — see ICH E6 (GCP) and OECD/GLP
- Does not address diagnostic assay performance — see ISO 20916 for IVD clinical performance
- Does not define pharmacokinetic modelling requirements
Always verify against the current published text before relying on it for a submission or inspection.
Overview
ICH M10 harmonises the validation of bioanalytical methods and the analysis of study samples that support regulatory submissions of nonclinical and clinical pharmacokinetic, toxicokinetic, and related data. It applies to chromatographic assays (such as LC-MS) and ligand-binding assays, and it specifies the validation parameters to be demonstrated — selectivity, specificity, calibration curve, accuracy, precision, matrix effects, carry-over, dilution integrity, and stability — together with acceptance criteria for validation and for routine study sample analysis. It also defines incurred sample reanalysis (ISR) and the documentation expected for methods and study data.
Legal basis & how it acquires force
M10 takes effect through regional adoption by ICH members — an FDA guidance for industry, an EMA/CHMP-adopted guideline, and equivalents elsewhere — and it supersedes or harmonises prior regional bioanalytical guidances. It supports data submitted under GLP (nonclinical) and GCP (clinical) frameworks by defining the analytical reliability of the results those studies generate.
Document structure
| Part | Covers |
|---|---|
| Introduction and scope | Applicability to chromatographic and ligand-binding assays; nonclinical and clinical use |
| Method validation | Full and partial validation; selectivity, calibration, accuracy, precision, stability, matrix effects |
| Study sample analysis | Run acceptance criteria, calibration and QC handling, reanalysis rules |
| Incurred sample reanalysis | ISR design and acceptance criteria |
| Documentation and reporting | Records, audit trail, validation and analytical reports |
Key requirements
- Perform full validation covering selectivity, specificity, calibration curve, accuracy, and precision
- Establish the lower limit of quantification (LLOQ) and validated calibration range
- Evaluate matrix effect, carry-over, dilution integrity, and analyte stability
- Apply the 4-6-X (or 4-6-20) run-acceptance and calibration-standard acceptance criteria
- Conduct incurred sample reanalysis (ISR) and meet its acceptance criteria
- Document reagent and reference standard traceability, including critical reagents for LBAs
- Maintain complete audit trails and raw data for study sample analysis
Implementation tips
- Distinguish chromatographic vs ligand-binding requirements — M10 sets different expectations for each
- Plan ISR into the study up front; a failed ISR after the fact is difficult to remediate
- Lock stability coverage to the actual sample storage duration and conditions, not a generic window
- Keep the validation report and the sample-analysis reports cross-referenced for the assessor
International alignment
M10 is harmonised across ICH members and implemented as regional guidance by FDA, EMA, PMDA and others, aligning previously divergent bioanalytical expectations into one standard for chromatographic and ligand-binding methods.
ICH M10: frequently asked questions
Quick answers to common questions about ICH M10.
Which assay types does M10 cover?
Chromatographic assays (e.g. LC-MS) and ligand-binding assays, with parameter expectations tailored to each.
Is incurred sample reanalysis required?
Yes; M10 defines ISR and its acceptance criteria as part of study sample analysis.
Does M10 apply to both nonclinical and clinical studies?
Yes; it applies to bioanalytical data supporting nonclinical and clinical submissions.