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This article is the first of a series of articles detailing the development of near-infrared (NIR) methods for solid-dosage form analysis. Experiments were conducted at the Duquesne University Center for Pharmaceutical Technology to qualify the capabilities of instrumentation and sample handling systems, evaluate the potential effect of one source of a process signature on calibration development, and compare the utility of reflection and transmission data collection methods. A database of 572 production-scale sample spectra was used to evaluate the interbatch spectral variability of samples produced under routine manufacturing conditions. A second database of 540 spectra from samples produced under various compression conditions was analyzed to determine the feasibility of pooling spectral data acquired from samples produced at diverse scales. Instrument qualification tests were performed, and appropriate limits for instrument performance were established. To evaluate the repeatability of the sample positioning system, multiple measurements of a single tablet were collected. With the application of appropriate spectral preprocessing techniques, sample repositioning error was found to be insignificant with respect to NIR analyses of product quality attributes. Sample shielding was demonstrated to be unnecessary for transmission analyses. A process signature was identified in the reflection data. Additional tests demonstrated that the process signature was largely orthogonal to spectral variation because of hardness. Principal component analysis of the compression sample set data demonstrated the potential for quantitative model development. For the data sets studied, reflection analysis was demonstrated to be more robust than transmission analysis.