2014 Process Development Symposium

Successful Scale-up via Simulation of Production Vessels under Lab Conditions using PAT and Thermal Analysis.

In today’s world, the chemical and pharmaceutical industries face major challenges including globalization, environmental and safety regulations, shortening product life cycle and increased time and cost pressure for commercial releases. Breakthroughs in process operations and modeling are necessary to achieve energy and material efficiency gains supporting shorter development and scale up times. Those breakthroughs are made possible in part by the lab and plant scale use of process analytical technologies (PAT) and reactor systems optimally designed for real time in situ process monitoring and accurate control of processes. For more than twenty five years the RC1e reaction calorimeter has been the golden standard for process safety and characterization studies at lab scale. Similarly, ATR-FTIR has become a mainstream PAT used by thousands of engineers and chemists around the world thanks to the success in the development of the well-known ReactIR technology. Over the past five years, METTLER TOLEDO has focused its research and development effort and investment around innovative and state-of-the-art technologies. For example,

  • Real time calorimetry (RTCal),
  • Expanded system platform for calorimetry investigation (volume, vessel, mixing options),
  • Plug-and-play ReactIR instrument,
  • Advanced chemometrics and prediction algorithm (mixing, kinetics, process safety, quantitative modeling and characterization)

    • They have now become the norm in R&D academic and industry labs. Several case studies will presented including for example,

    • Automated control of dosing rate at lab scale according to plant cooling capabilities using RTCal and advanced predictive models
    • Rapid process optimization using lab scale calorimetry, automation, and numerical simulation of thermal and mixing behavior of industrial reactors
    • In-silico optimization of dosing rate at plant scale based on a kinetic model developed using quantitative ATR-FTIR results
    • Qualitative use of reaction heat on a small scale to screen experimental conditions and optimization reaction conditions
    • Predictive modeling and assessment of process safety profile (primary and secondary reactions) based on adiabatic and isothermal calorimetry experiments using advanced software algorithm (iC Safety).