Near-infrared spectroscopy (NIRS) is known to be a suitable technique for rapid fermentation monitoring. Industrial fermentation media are complex, both chemically (ill-defined composition) and physically (multiphase sample matrix), which poses an additional challenge to the development of robust NIRS calibration models. We investigated the use of NIRS for at-line monitoring of the concentration of clavulanic acid during an industrial fermentation. An industrial strain of Streptomyces clavu-ligerus was cultivated at 200-L scale for the production of clavulanic acid. Partial least squares (PLS) regression was used to develop calibration models between spectral and analytical data. In this work, two different variable selection methods, genetic algorithms (GA) and PLS-bootstrap, were studied and compared with models built using all the spectral variables. Calibration models for clavulanic acid concentration performed well both on internal and external validation. The two variable selection methods improved the predictive ability of the models up to 20%, relative to the calibration model built using the whole spectra. (c) 2005 Wiley Periodicals, Inc.