Date: April 10, 2026
FDA’s Center for Drug Evaluation and Research, in cooperation with the Center for Biologics Evaluation and Research, has issued Bioanalytical Method Validation for Biomarkers as a final Level 2 guidance dated April 2026 (docket FDA-2017-D-6821). The HHS guidance portal lists an issue date of April 10, 2026. FDA first issued the guidance in January 2025, and the April 2026 text keeps the same three sections and the same recommendations. It makes ICH M10 the starting point for validating biomarker assays, although M10 itself excludes biomarkers from its scope.
The guidance applies to methods that measure in vivo biomarker concentrations in matrices such as blood or urine for INDs, NDAs, BLAs, their supplements and ANDAs, and it can also inform methods for nonclinical study samples (Section I). Section II says the May 2018 guidance Bioanalytical Method Validation “will be withdrawn” upon publication of this guidance; FDA still lists it as final.
Section III sets the extent of validation by the decision the data support. When biomarker data support regulatory decision-making, such as a pivotal determination of safety or effectiveness or dosing instructions in labeling, the assay “should be fully validated” as described in M10. For internal decisions such as candidate selection or proof of concept, sponsors apply “the extent of method validation they deem appropriate.” The guidance names accuracy, precision, sensitivity, selectivity, parallelism, range, reproducibility and stability as important characteristics that define the method, recognizes that some M10 criteria “might not be applicable to some biomarker analyses,” and encourages sponsors to justify those differences in their method validation reports.
What it means for calibration
For a biomarker assay that supports a regulatory decision, M10 sets the default calibration design. For chromatographic methods, M10 Section 3.2.4 calls for at least six concentration levels of calibration standards, including the LLOQ and the ULOQ, and states that the regression model, weighting scheme and transformation “should be determined during the method validation.” Section 4.2.3 sets the calibration curve requirements for ligand binding assays. In practice, that means justifying in the validation report any M10 calibration criterion the lab does not apply, and bringing an assay first validated only for internal decisions to full M10 validation before its data support a regulatory decision.
When a biomarker is an endogenous molecule, a matrix without interference may not be available. M10 Section 7.1 describes four approaches for that case: surrogate matrix, surrogate analyte, background subtraction and standard addition. Standard addition “is only applicable for analytical platforms with linear responses” (Section 7.1), and parallelism “should be evaluated in the Surrogate Matrix and Surrogate Analyte Approaches” (Section 7.1.3). In practice, the calibration record for an endogenous biomarker should name the approach, the calibrator matrix and the parallelism data linking the surrogate and authentic matrix.
Source: fda.gov, Bioanalytical Method Validation for Biomarkers (final guidance, April 2026)
Also see: fda.gov, Bioanalytical Method Validation for Biomarkers, guidance document (April 2026); hhs.gov, HHS guidance portal entry for Bioanalytical Method Validation for Biomarkers (issue date April 10, 2026); hhs.gov, Bioanalytical Method Validation for Biomarkers (January 2025 version); ich.org, M10 Bioanalytical Method Validation and Study Sample Analysis (Step 4, May 24, 2022)
Part of the WLTR ICH M10 guide for pharmaceutical and bioanalytical labs. This is a plain-language summary, not regulatory advice. Confirm requirements with the issuing agency and your quality unit. Questions or a different read on this change? Leave a comment below.