Process characterization using QbD approaches has rarely been described for precipitation steps used for impurity removal in biopharmaceutical processes. We propose a two-step approach for process characterization in which the first step focuses on product quality and the second focuses on process performance. This approach provides an efficient, streamlined strategy for the characterization of precipitation steps under the Quality by Design paradigm. This strategy is demonstrated by a case study for the characterization of a precipitation using sodium caprylate to reduce host cell proteins (HCP) during a monoclonal antibody purification process. Process parameters were methodically selected through a risk assessment based on prior development data and scientific knowledge described in the literature. The characterization studies used two multivariate blocks to decouple and distinguish the impact of product quality (e.g., measured HCP of the recovered product from the precipitation) and process performance (e.g., step yield). Robustness of the precipitation step was further demonstrated through linkage studies across the overall purification process. HCP levels could be robustly reduced to ≤100 ppm in the drug substance when the precipitation step operated within an operation space of ≤1% (m/v) sodium caprylate, pH 5.0-6.0, and filter flux ≤300 L/m -hr for a load HCP concentration up to 19,000 ppm. This two-step approach for characterization of precipitation steps has several advantages, including tailoring of the experimental design and scale-down model to the intended purpose for each step, use of a manageable number of experiments without compromising scientific understanding, and limited time and material consumption.