The goal of this project is to increase emergency preparedness to respond to a mass casualty radiological/nuclear incident through the development of a biodosimetry triage device. Under the parent NIAID U01 award, the ASELL team is developing CellRADx, a point-of-care biodosimetry triage device that incorporates Complete Blood Count (CBC) with WBC differential, along with the detection of extracellular and cell-surface biomarkers of radiation exposure. This triage device will incorporate an exposure assessment algorithm also being advanced under the parent award, that can utilize inputs from CBC differential measurements from any appropriate source. To date, iterations of the CellRADx algorithm functionally based on the HARI algorithm have shown promising performance at dose determination, especially in the later time periods. Under this Administrative Supplement, ASELL proposes to improve the performance of the algorithm based on feedback from the FDA and release of a new FDA guidance document on the credibility of simulated data. The additional tasks proposed herein; therefore, are Algorithm Performance Improvements, and demonstrating the credibility of our In Silico Acute Radiation Blood Cell Depletion Model. Areas of algorithm improvement include: 1) use of alternative algorithm equations, 2) incorporation of time effects into the algorithm, and 3) incorporation of demographic effects into the algorithm. To address the practical limitations of available human clinical data, ASELL will pursue use of an in silico hematopoietic cell depletion model to be used in combination with retrospective real-world human data sources to build a “virtual clinical cohort” for future clinical studies. ASELL intends to follow the recently released (November 2023) FDA Guidance “Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions.” These tasks will address regulatory inputs and collectively strengthen development and validation of CellRADx as a qualitative biodosimetry tool for large- scale radiation triage.