In-line monitoring of continuous powder flow is an integral part of the continuous manufacturing process of solid oral dosage forms in the pharmaceutical industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders and/or continuous mixers provides important data about the state of the process. Such measurements support control of the process and thereby enhance product quality. Near Infrared Spectroscopy (NIRS) is a potential PAT tool to monitor the homogeneity of a continuous powder flow stream in pharmaceutical manufacturing. However, the association of analytical results from NIR sampling of the powder stream and the homogeneity (content uniformity) of the resulting tablets provides several challenges; appropriate sampling strategies, adequately robust modeling techniques and poor sensitivities (for low dose APIs) are amongst them. Information from reflectance-based NIRS sampling is limited. The region of the powder bed that is interrogated is confined to the surface where the measurement is made. This potential bias in sampling may, in turn, limit the ability to predict the homogeneity of the finished dosage form. Further, changes to the processing parameters (e.g., rate of powder flow) often have a significant effect on the resulting data. Sample representation, interdependence between process parameters and their effects on powder flow behavior are critical factors for NIRS monitoring of continuous powder flow system. A transmission NIR method was developed as an alternative technique to monitor continuous powder flow and quantify API in the powder stream. Transmission NIRS was used to determine the thickness of the powder stream flowing from a loss-in-weight feeder. The thickness measurement of the powder stream provided an in-depth understanding about the effects of process parameters such as tube angles and powder flow rates on powder flow behaviors. This knowledge based approach helped to define an analytical design space that was specific to flow properties and to determine the optimum process parameters for successful quantitation of powder stream. A PAT method based on transmission NIRS was developed to monitor the homogeneity of API in a continuously flowing powder stream.