The statistical framework to systematically detect mean stationarity in the context of continuous manufacturing is described in this article. The methods presented in this article use econometric and financial time-series analysis concepts in the form of unit-root and stationarity hypothesis tests. The tests under discussion are the augmented Dickey-Fuller, Philips-Perron, Leybourne-McCabe, and Kwiatkowski-Phillips-Schmidt-Shin. These hypothesis tests are evaluated on data generated by a focused-beam reflectance measurement sensor implemented on-line in a continuous plug-flow crystallizer. This contribution has shown that the hypothesis tests can be used to detect steady-state conditions on-line in a plug-flow crystallizer. Furthermore, this econometric framework can be used as a mean stationarity certificate of collected samples to document that the process was mean stationary during the sampling. The statistical framework described in this article can be applied to any continuously operated unit operation or sensor measurement. (c) 2018 American Institute of Chemical Engineers AIChE J, 64: 2426-2437, 2018