ABSTRACT The goals of the MPS Qualification Program for the TRaCe-bMPS is to develop five FDA qualified drug development tools (DDTs) that provide functional information important to the evaluation of drugs targeting tissue barrier function in disease. Transport of cells and molecules across an interface (or barrier) between tissues is a critical step in infection and inflammation and a key target in drug development. The ideal platform for the discovery and efficacy studies of drugs targeting barrier function should have the following features: use extremely thin, highly permeable and optically transparent membranes to support the culture of cells and deposition of natural or synthetic extracellular matrix; enable culture of multiple cell types, provide measurement of multiple outputs; offer the ability to make measurements over time using the same system; have the capability of exposing tissue structures to physical forces, and enable multiplexing for medium throughput applications. Existing commercial systems including the gold standard TranswellTM and tissue chips sold by Emulate, Mimetas, and SynVivo, suffer limitations that prevent them from being the general solution to a barrier function based DDT. The core technology of the TRaCe-bMPS is a modular platform, known as the µSiM (microphysiological system featuring a silicon membrane) that has the ideal characteristics of a barrier-based platform while being scalable, flexible, and reliable in addressing this unmet need. For the qualification process in the TRaCe-bMPS, we will establish the following DDTs to assess the efficacy of drugs targeting barriers relevant to the treatment of: 1) central nervous system (CNS) disorders, 2) fibrosis, 3) musculoskeletal autoimmune disease, 4) sepsis, and 5) osteomyelitis. To advance these DDTs towards qualification, we will (1) place all systems within a common platform that can be used in a multi-well format amenable to moderate throughput (12-24 well assays) using a common microscopy and imaging system; (2) validate using a set of current drug treatments known to affect specific pathways for the MPS disease models; (3) establish a set of standard operating procedures (SOPs); and (4) establish reproducibility by having two laboratories obtain results following the SOP. We will then prepare and submit FDA qualification packages for each of the five DDTs. Completion of these aims will provide qualified DDTs with advanced functional assays using well-characterized human cells that will enable critical insight into the role specific drugs on barrier and tissue function and lead to community adoption. We expect that the qualification process will uncover additional needs to evaluate functional outcomes, leading to new or modified MPS that address each of these context of use cases.