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Integration of process analyzers and process automation together with the use of multivariate tools for design, data acquisition and analysis is critical and listed in Food and Drug Administration (FDA) guidance of Process Analytical Technology (PAT). Their use helps conduct information-rich experiments that respond to the need for increased process development throughput, downstream consistency and reliability: https://www.mt.com/global/en/home/app... Technical breakthroughs for better understanding and characterization of chemical or biochemical process are necessary to meet today’s challenges posed to the pharmaceutical and fine chemicals industries. Proper integration of process analyzers and process automation together with the use of multivariate tools for design, data acquisition and analysis is critical and listed in FDA guidance of Process Analytical Technology (PAT). Their use helps conduct information-rich experiments that respond to the need for increased process development throughput, downstream consistency and reliability. PAT case studies include the trifluoroacetylation of a lactol derivative was investigated using real time in situ Fourier Transform Infrared (FTIR). Conditions were determined which lead to high level of dimer impurity, help identify critical process parameters, and obtain kinetic information in real time; heat generation of an anionic acrylamide (ACM) inverse emulsion polymerization was evaluated. This enabled the determination of differences in the rates of reaction of less inhibited acrylamide relative to standard acrylamide; The supersaturation of paracetamol during crystallization experiments was monitored in real time using in situ Fourier Transform Infrared (FTIR) and multivariate chemometric techniques for quantitative analysis. Integrating these PAT tools into a computer controlled reaction vessel allowed a better control of experimental conditions, as well as a faster and more intuitive protocol to collect data points, build a calibration model, and apply the model to monitor supersaturation in real time.