Xylazine is a synthetic non-opioid alpha2-adrenergic agonist that has contributed increasingly to overdose deaths in the United States in recent years. CDC estimates the number of overdose deaths in the US involving xylazine increased 1238% from 2018 to 2021. Fentanyl laced with xylazine has been declared an emerging threat to the US. Xylazine can cause serious skin ulcerations, profound mental status depression and serious and extended withdrawal effect, which do not respond to naloxone treatment. It is imperative to alert emergency medical service personnel and clinicians of xylazine’s presence when treating opioid overdoses. Despite the clinical and public health needs, there is currently no rapid diagnostic for xylazine detection. The only commercially available test strip is only useful for drug powder checking, not diagnostic use. In this fast-track proposal, we propose to develop and commercialize the first regulatory approved rapid xylazine diagnostic screening device (InstaStrip-Xylazine), from prototype development all the way to regulatory submission. The technology is based on a platform for rapid and high sensitivity detection of drug analytes that is developed and patented by the team. We have a track record of successfully developing a rapid diagnostic for fentanyl using this technology platform. Leveraging the same platform, we have generated an InstaStrip-Xylazine prototype with 20 times higher sensitivity than the only commercially available strip in a head-to-head comparison. In Phase I, we will work on developing and optimizing the prototype under Quality Management System (QMS) and Design Control, using an internally developed antibody to further achieve the clinically ideal cutoff of <10 ng/mL. We will also conduct preliminary clinical validation and conduct pre-submission meeting with FDA to finalize regulatory pathway. In Phase II, we will partner with FDA-registered contract manufacturer to produce three device lots, conduct verification and validation studies, including analytical and method comparison studies. We will also enroll end users in a study to evaluate the usability of the device. Data generated during phase II will be used for regulatory submission. After completion of the Blueprint Program, the immediate next step is the submission of regulatory approval/clearance application to FDA for CLIA waiver and over-the-counter (OTC) use. Although the project focuses on xylazine, the technology and the resources developed in this proposal will serve as a blueprint to allow Instanosis to quickly modify the technology for other analytes and respond rapidly to other emerging drug threats.

Xylazine is a synthetic non-opioid alpha2-adrenergic agonist that has contributed increasingly to overdose deaths in the United States in recent years. We propose to develop and commercialize the first regulatory approved diagnostic device for rapid xylazine detection, using our patent pending InstaStrip technology. The resources developed in this proposal will serve as a blueprint to allow us to quickly modify the technology for other analytes and respond rapidly to emerging drug threats.