PII-006 - A SNAPSHOT OF PHARMACODYNAMIC BIOMARKERS BIOANALYSIS IN 16 BLAS APPROVED FOR NEUROLOGY INDICATIONS.

Y. Lee¹, X. Du¹, Y. Wang²; ¹U.S. Food and Drug Administration, ²U.S. Food and Drug Administration, Silver Spring, United States.

Background: The objective is to survey the landscape of PD biomarkers in the regulatory submissions of neurologic drug products and their method validation profiles. Evaluation of the current state of PD biomarkers bioanalysis can inform future best practice.

Methods: Sixteen BLAs from 2017-2022 for neurology indications were reviewed for their PD biomarkers and analyzed if they met two criteria: listed in their labels and had bioanalytical method validation reports. The validation parameters for each biomarker were analyzed for 1) the 7 key analytical parameters (accuracy, analytical measurement range (AMR), parallelism, precision, selectivity, specificity, stability) mentioned in the Critical Path (CP) Institute’s Points to Consider Document (2019) and if evaluated in their reports 2) concordance of method validation with the recommendations in “Bioanalytical Method Validation Guidance for Industry” (2018), 3) types of parameters tested across different method platforms and 4) relationship between PD biomarkers , clinical studies, context of use (COU), bioanalytical methods and parameters. Resources included product labels, clinical studies, and validation reports.

Results: Six BLAs approved for three diseases contained PD biomarkers that met selection criteria, specifically, 18/46 biomarkers. Each of the 18 biomarkers assessed a subset of those 7 key analytical parameters, ranging from 2 parameters for 8 biomarkers to 6 parameters for 2 biomarkers. Across all 18 biomarkers, the number of biomarkers tested for each of the 7 key analytical parameters varied: accuracy (9), AMR (10), parallelism (9), precision (18), selectivity (7), specificity (0), and stability (12). The number of parameters tested differed across six bioanalytical method platforms, ranging from 2 for 1 platform to 6 for 2 platforms. Compared to the recommendations for validation parameters, the tested parameters demonstrated variability in adherence. The highest percentage of adherence was with precision followed by stability. The relationship between PD biomarkers, clinical studies, COU, bioanalytical methods, and parameters conveyed heterogeneity across all 18 biomarkers.

Conclusion: The survey results conveyed heterogeneity in biomarker bioanalysis and further work is necessary to develop best practice.