ICH M10 (International Committee of Harmonization Multidisciplinary guideline) provides guidance on bioanalytical method validation and study sample analysis for the measurement of chemical and biological human drugs and their metabolites in biological samples. Such pharmacokinetic/toxicokinetic data serve as the basis for regulatory decisions on the safety, dosage, and regimen of new drugs.
To date, there have been several regional regulatory guidelines, such as the FDA Bioanalytical Method Validation Guidance, May 2018 and EMA Guideline on Bioanalytical Method Validation, July 2011, among many others. These guidelines required compliance and continual tracking of updates for international clinical trials. Global implementation of the ICH M10 is not here yet, but has started in many regions, including at the FDA and EMA, aiming at providing one single harmonized approach to bioanalysis.
Well-characterized, appropriately validated, and carefully documented bioanalytical methods are essential to ensure reliable data.
The scope of the ICH M10 guideline specifically focuses on pharmacokinetic and toxicokinetic analysis of human drugs under development in both non-clinical GLP and clinical trials. The guideline intends not to cover immunogenicity and biodistribution for cell and gene therapy or biomarkers. This is in contrast with the previous FDA BMV guidance, which includes a small section on biomarkers. Therefore, it is recommended that methods for biomarkers be validated according to their context of use, based on the best practices of the FDA BMV 2018 guidance and the C-Path Institute.
The M10 guideline is principally designed for LC-MS and immunoassays. For immunoassays, the new guidance contains rather minor changes regarding method validation and sample analysis but provides clarification on some technical and documentation aspects.
For example, QC samples should physically bracket in-study samples. This guideline also opens the door to singlicate analysis of in-study samples where scientifically justified. In line with the Reduce, Refine, Replace (3 Rs) principles but also due to the increased lead times and costs of obtaining non-human primate (NHP) matrices since the COVID-19 pandemic, these are now considered rare and will be replaced by surrogate matrices where scientifically justified. Expiry dates of critical reagents can be extended if appropriately monitored and documented, otherwise lyophilization of critical reagents may be an option. Last but not least, the M10 guideline gives clarity for cross-validation and statistical methods for assessing agreement between different methods or different laboratories, within a study or across studies that are to be combined for regulatory decisions.
In terms of documentation, a formal method development report is not required but data, supporting the selection of the MRD (minimal required dilution) should be available if requested by the regulatory authorities.
The adoption of the ICH M10 guideline marks a significant shift from multiple guidelines to a unified approach, facilitating global standardization of bioanalytical methods. The M10 guideline has been implemented by National Regulatory Authorities (NRAs) such as the EMA (effective 21 January 2023), Health Canada (20 January 2023), Swissmedic (25 May 2022) and the US FDA (7 November 2022) and is being implemented by other NRAs. Implementation will be accompanied by additional Q&A documents to provide additional clarification and to promote convergence and improved harmonization of bioanalytical method validation and study sample analysis. It is important to remember that regulators are inclined to consider any approach/interpretation if it is supported by good science.
It is encouraging to see several regulatory agencies adopting similar guidelines to streamline bioanalytical approaches. At Active Biomarkers, we see this as a great opportunity to increase consistency in method validation and sample analysis. However, high quality science and expertise remain fundamental to supporting preclinical and clinical analysis.