The effective biotechnological process development depends on the system for monitoring the activity of the culture during cultivation. The feasibility of monitoring the metabolic flux during the cultivation of Bacillus thuringiensis var. galleriae (Btg) in pilot scale bioreactor was studied. All possible sources of heat generation and transfer in the system were accounted to determine the metabolic heat flux caused by the culture alone. Successful demonstration of the heat measurements has revealed the scale-up characteristics of microbial process based on the heat generation data. In addition, influence of complex media sources on heat flux, sporulation and insecticidal crystal protein (ICP) synthesis was understood, Nature of the microbial process has necessitated fed-batch cultivation with glucose solution feeding in proportions to the metabolic heat production rate and subsequent optimization of the feeding glucose solution concentration had resulted in an enhanced ICP concentration. As a significant outcome, heat flux into the cooling water for the maintenance of bioreactor temperature was found to be in definite correlation with the metabolic heat production rate. This allowed an opportunity for understanding the metabolic status of the culture with continuous on-line monitoring of the temperature profile of the cooling water in industrial scale fermentation with cost effectiveness. Continuous assessment of cultures through heat flux could be exploited by enhancing the desired metabolic process(s) in industrial scale fermentation.