Crucial ICH M10 Bioanalytical Method Validation Guidelines
International Council for Harmonisation (ICH) has made guidelines available for bioanalytical method validation. ICH method validation guidelines are accepted as standard by most major organizations, including the EMA and FDA.
The guidelines are intended as recommendations for bioanalytical assays along with chemical and biological drug quantification and their application. It should be noted that these are non-binding guidelines. A departure from the guidelines is acceptable in the presence of appropriate scientific justification.
ICH Method validation for bioanalytical assays is often a regulatory requirement. These guidelines present an acceptable path to such validation. Adherence to GxP, as necessary for specific requirements, should be followed along with the ICM M10 bioanalytical method validation guidelines.
Method Development
ICH M10 method development guidelines recommend a focus on the following characteristics for method development.
- Reference standards
- Minimum Required Dilution (MRD)
- Critical reagents
- Calibration curve
- Selectivity and specificity
- Sensitivity
- Accuracy
- Precision
- Recovery
- Stability of the analyte in the matrix
- Quality control samples (QCs)
Interestingly, there is no need for extensive documentation. However, any changes, issues, and resolutions should be recorded.
Method Validation
The larger objective with M10 is to define each parameter and its acceptance criteria for method validation. Defining each partial or cross-validation and establishing requirements for reference standards and critical reagents is also considered.
Full method validation is necessary to ascertain the reliability of results and the acceptability of assay performance. Full method validation should be performed when establishing a bioanalytical method development. It is also recommended for reporting the analytical method in literature or repurposing a commercial kit for bioanalytical use in drug development.
Chromatographic methods and Ligand Binding Assays should focus on individual/specific parameters and elements for validation.
Partial Validation
This is used/needed to evaluate any modifications to the fully validated bioanalytical method.
Cross-Validation
This is used only in specific circumstances, for example:
- Following different methods within a study
- Following the same method but in a different laboratory/location
- Using different methods across studies
Chromatographic Assay Validation
The draft ICH M10 guidelines take a special interest in chromatographic assay validation and LBAs. For chromatographic assay validation, the principles remain the same as those described here. The focus moves to more specific scenarios important for chromatographic assays.
Five main elements of method validation could be considered for these assays.
- Including at least two freeze-thaw cycles
- Demonstrating the stability of the analyte in the biological matrix at the expected storage temperature
- Accuracy and precision at a minimum of five replicates should be demonstrated
- Establishment of a standard curve to manage expected sample concentrations
- Determining the relationship for simple response versus concentration
While these listed factors form the important factors to consider, the ICH method validation draft presents several other applicable points as well.
Ligand Binding Assay Validation
Validation parameters for Ligand Binding Assays (LBA) are generally in line with the listed expectations for chromatographic assays. However, some changes are made to suit the LBA method in a better way. These are generally related to critical reagents, specificity, and calibration curves.
Though it is a draft guideline at the moment, the ICH M10 has generally received a favorable response from stakeholders. There are slight differences between the FDA and EMA drafts of the guidelines, but they stay true to major points in the ICH M10 bioanalytical method validation guidelines.