A desired goal of the FDA's PAT framework is to design and develop well understood processes that will consistently produce a pre-defined product quality. The technology tools that support achievement of this goal can be classified into four main areas: multivariate data analysis, process analyzers, process automation and control, and knowledge management. Process analyzers have played a significant role in chemical manufacturing by providing “real time” measurement of product quality attributes which enable the process operating parameters to be continuously adjusted to maintain optimal process efficiency and product quality. High Performance Liquid chromatography (HPLC) has historically been an important analytical tool in the pharmaceutical industry laboratory for measuring product quality and can play a valuable role in on-line process monitoring as well. Utilizing examples from process scale, ion exchange chromatography and an enzyme mediated product conversion reaction, this presentation will discuss how on-line HPLC has been utilized as an enabling technology for process automation and control resulting in increased process efficiency and reduced process variability.