In this paper, a multi-point fiber optic based NIR system was implemented to monitor API concentration at the discharge of a continuous mixer. The sample size being interrogated by NIR was determined by measuring the velocity of the powder on the chute, which allowed selection of the number of scans to be averaged. A methodology was developed that allows quantification of the error associated with the in-line measurements. Comparison of in-line and off-line measurements was made at equivalent sample sizes. Mathematical model fitting for the in-line as well as off-line data revealed that the contribution of the analytical method error was negligible. A baseline RSD of 0.02 in the in-line measurements persists because of the inherent non-uniform nature of powder material. These results are useful towards achieving Real-Time-Release (RTR) of continuously manufactured drug product. (c) 2013 Elsevier B.V. All rights reserved.