FDA CRL - Orexo AB

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Orexo AB concerning their New Drug Application (NDA) for Naloxone hydrochloride nasal powder. The application could not be approved due to significant deficiencies primarily related to the device and human factors. A main issue was that the final finished commercial device was not adequately tested for verification, reliability, stability, and shipping, showing differences from the versions that were tested. Crucially, the human factors validation study revealed the device's user interface does not support safe and effective use. Participants demonstrated critical use errors, close calls, and difficulties depressing the plunger, often believing they had administered a dose when they had not. This could lead to no dose delivery, posing a serious risk of increased mortality for patients. Orexo AB must implement user interface revisions, provide data demonstrating the safety and effectiveness of the redesigned product, and submit a new human factors validation study protocol for FDA review. Additionally, a comprehensive safety update must be included, and prescribing and carton/container labeling will be reviewed once other issues are resolved. Orexo has one year to resubmit a complete response addressing all identified deficiencies.