Scale-up of the Efrotomycin fermentation using a computer-controlled pilot plant

Abstract

A description is given of the application of computer process control and on-line data aquisition for the rapid scale-up of the Efrotomycin fermentation. This process involves the use of a pseudo-mycelial culture, solids and oil containing medium, and exhibits a high degree of sensitivity to small changes in sterilization conditions. The latter point presented the major scale-up challenge, especially when batch sterilization of medium was used. An example is given of how on-line computer-generated data were used to monitor overall metabolic changes and how this information was used to make process control decisions during the fermentation.

The agitator speed was automatically controlled at the larger scale to maintain the required dissolved oxygen concentration and this enabled us to rapidly scale-up based on constant oxygen transfer coefficient. The necessary accuracy of control of sterilization conditions required at the various different scales of operation could only be met by use of continuous HTST (high temperature short time) sterilization of the medium. In addition, use of the continuous sterilizer made it much easier to specify conditions for different scales of operation.