Project Summary/Abstract This Fast-Track SBIR proposal will help make significant inroads towards commercializing Rescue Biomedical LLC's automatic antidote delivery device (A2D2) in order to combat opioid overdose-related deaths. Despite increasing awareness of the dangers associated with opioids, there were more than 70,000 deaths due to opioid overdose in 2020. In addition, the rising popularity of illegal synthetic opioids and social isolation due to the ongoing COVID-19 pandemic is fueling a third wave of opioid-related deaths. Since these illegal drugs are orders of magnitude more potent than morphine and can cause respiratory failure in minutes, there is very little time for users to identify and respond to the symptoms of overdose with antidotes like naloxone. The proposed A2D2 is a low-cost and simple subcutaneous drug delivery capsule that can automatically detect opioid- induced respiratory failure and release naloxone in a closed-loop manner. It will extend the lifetime of overdosed patients so that they can receive proper medical care. In this Fast-Track SBIR proposal, Rescue Biomedical seeks to validate its hypothesis that there is a significant demand for a wearable-implantable combinational device for automatically detecting and treating opioid overdose. In Phase I, Rescue Biomedical will work with its collaborator at Indiana University School of Medicine to quantify users' willingness to use wearable and implantable devices. Furthermore, clinicians and other stakeholders (e.g., Licensed Chemical Dependency Counselor) will be identified to understand their willingness to recommend advanced harm reduction devices. Finally, Rescue Biomedical will leverage the cohort of these stakeholders to validate the overall system design to ensure high compliance and usability. In Phase II, efforts will be focused on technical integration and performing a pivotal pre-clinical experiment to demonstrate the closed-loop capabilities to reverse the effects of opioid overdose. Moreover, Rescue Biomedical will focus efforts for commercialization including regulatory submissions for IND/IDE submission and performing design verification and validation based on user feedback.