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A computational thermal fluid dynamic (CTFD) model has been developed to model all processing steps, including the vertical pressure vessel, an internal polymeric carrier, and food packages in an axis\u2010symmetric geometry. Heat transfer and fluid dynamic equations were coupled to four selected kinetic models for the inactivation of <jats:italic>C. botulinum<\/jats:italic>; the traditional first\u2010order kinetic model, the Weibull model, an nth\u2010order model, and a combined discrete log\u2010linear <jats:italic>n<\/jats:italic>th\u2010order model. The models were solved to compare the resulting microbial inactivation distributions. The initial temperature of the system was set to 90\u00b0C and pressure was selected at 600 MPa, holding for 220 s, with a target temperature of 121\u00b0C. A representation of the extent of microbial inactivation throughout all processing steps was obtained for each microbial model. Comparison of the models showed that the conventional thermal processing kinetics (not accounting for pressure) required shorter holding times to achieve a 12D reduction of <jats:italic>C. botulinum<\/jats:italic> spores than the other models. The temperature distribution inside the vessel resulted in a more uniform inactivation distribution when using a Weibull or an <jats:italic>n<\/jats:italic>th\u2010order kinetics model than when using log\u2010linear kinetics. The CTFD platform could illustrate the inactivation extent and uniformity provided by the microbial models. The platform is expected to be useful to evaluate models fitted into new <jats:italic>C. botulinum<\/jats:italic> inactivation data at varying conditions of pressure and temperature, as an aid for regulatory filing of the technology as well as in process and equipment design. \u00a9 2009 American Institute of Chemical Engineers Biotechnol. 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