The document discusses the potential role of mathematical modeling tools in improving regulatory communications on quality by design in the pharmaceutical industry. Specifically, it argues that chemometrics, pharmacometrics, and econometrics can provide objective ways to integrate scientific data across the product lifecycle in order to facilitate more risk-based regulatory decisions. Development reports that utilize chemometrics to predict critical quality attributes and verify predictions, along with explanations connecting these attributes to clinical outcomes, can give regulators a means to evaluate scientific understanding. Econometric modeling of manufacturing practices and their impact on product variability may allow facilities to be categorized by risk level. This integrated approach using multiple disciplines can help realize the goals of quality by design.