PROJECT SUMMARY/ABSTRACT In 2019, the Food and Drug Administration issued approvals for generic combination products including the Fluticasone and Salmeterol Inhalation Powder and the Naloxone Nasal Spray. Generic devices like these have the potential to cause harm to a patient or user if the user interface is not carefully evaluated to ensure a generic product’s user interface is substitutable when compared to that of its reference listed drug (RLD). Understanding the factors that could impact safe and effective use is critical when evaluating a generic combination product as there is a higher likelihood for use error resulting from a user’s pre- existing mental model, based on use experience with the RLD. Additionally, the reliance of an abbreviated new drug application (ANDA) on FDA’s findings that the RLD is safe and effective relies on the premise that there are no user interface differences that would undermine the therapeutic equivalence of the generic to the RLD. Battelle applies a risk-based human-centric design (HCD) approach to medical device development that predates FDA guidance on the subject. Battelle will modify this approach to develop methods for effectively evaluating a generic device against an RLD. Battelle will collaborate with the federal research team to accomplish the following two (2) aims: Aim 1: Develop enhanced methods for threshold analysis and categorization of user interface differences. Battelle will leverage extensive device development and human factors expertise to collaborate with the FDA to develop a risk-based approach to support the categorization of differences in the design of a user interface. Battelle will select specific representative combination products for analysis. Battelle will implement or modify their existing usability engineering (UE) methods to perform use risk analyses of key elements of the selected devices to support the appropriate categorization of the user interfaces. Aim 2: Establish effective methods for assessing “other” design differences.” Battelle will utilize their in- house expertise to develop custom methods for evaluation and data collection. Combined with Battelle’s experience developing creative modeling solutions for a variety of human tissue types, Battelle will produce methods that will accurately assess whether "other" differences in the user interface introduce a risk that might impact the clinical effect or safety profile of the generic drug-device combination product as compared to the RLD. The evaluation methods developed by Battelle and the federal research team will be applicable for all stakeholders engaged in the development of generic drug-device combination products. This effort will result in an improved set of tools for evaluating how differences in the user interface of a proposed generic combination product as compared to the RLD may impact the overall use of a product.