Biomarkers and Precision Medicine Community (BPMC)

Hello everyone,

The FDA have just published this guidance for industry: Bioanalytical Method Validation for Biomarkers Guidance

I leave you all to read and digest.

Personally, I am disappointed that after all the discussions involving industry and regulatory colleagues on the best scientific practices for biomarker assay establishment and validation, this guidance refers to the ICH M10 PK method validation document and does not include any discussion on the key starting point for biomarker method establishent: understanding the biology of the biomarker and anticipated changes with treatment...

Cross-posting reply originally posted in Bioanalytical Community:

Thanks for posting, Rob. 

For our community, I'd like to offer some perspective.  Those of us engaged in biomarker assay development and validation are well aware that the varied contexts of use for biomarker assays cannot be captured in a one size fits all guidance. I want to caution those who may be viewing this guidance as a mandate to use the specific experimental approaches described for PK assays in M10, which itself clearly puts biomarker assays out of scope. Instead, I would view this as indicating that the parameters of interest for quantitative/relative quantitative assays are similar and we should scientifically stand behind our approaches.  This is what we have been doing all along for our biomarker assays - and quite successfully.  I have never failed to gain successful regulator alignment when using a context of use driven approach for biomarkers.

I'd also like to highlight that this Guidance simply indicates that nothing has changed from what FDA put in the 2018 Guidance: 

In the 2018 Guidance, FDA stated:

"Method validation for biomarker assays should address the same questions as method validation for drug assays. The accuracy, precision, sensitivity, selectivity, parallelism, range, reproducibility, and stability of a biomarker assay are important characteristics that define the method. The approach used for drug assays should be the starting point for validation of biomarker assays, although the FDA realizes that some characteristics may not apply or that different considerations may need to be addressed."

In the current Biomarker Guidance, FDA states: 

"Method validation for biomarker assays should address the same questions as method validation for drug assays. The accuracy, precision, sensitivity, selectivity, parallelism, range, reproducibility, and stability of a biomarker assay are important characteristics that define the method. The approach described in the guidance for industry M10 Bioanalytical Method Validation and Study Sample Analysis (November 2022) for drug assays should be the starting point for validation of biomarker assays, especially chromatography and ligand-binding based assays."

All that has changed is that M10 has been adopted for drug concentration assays, so now FDA points there instead of to its own BMV guidance.

As an industry, we have made great progress in implementing COU-driven biomarker assay validation, even while the 2018 FDA Guidance was in effect.  This new guidance changes nothing and should not alter our trajectory.

Hello everyone,

The FDA have just published this guidance for industry: Bioanalytical Method Validation for Biomarkers Guidance

I leave you all to read and digest.

Personally, I am disappointed that after all the discussions involving industry and regulatory colleagues on the best scientific practices for biomarker assay establishment and validation, this guidance refers to the ICH M10 PK method validation document and does not include any discussion on the key starting point for biomarker method establishent: understanding the biology of the biomarker and anticipated changes with treatment...