In our previous works, the immobilized glucose oxidase (GO) plus manganese dioxide (MnO2) were prepared and efficiently used at 30 ◦C for production of calcium gluconate (CaG) in an external loop airlift. In the gel beads occurred the three reactions: (1) the GO-catalyzed air oxidation of glucose to produce gluconic acid (GA) and hydrogen peroxide (P) which inactivated GO, (2) the MnO2-catalyzed decomposition of P and (3) the neutralization of GA with calcium hydroxide added continuously resulting in accumulation of CaG at a constant pH. In this work, the stabilities of the immobilized GO and MnO2 activities to various operating conditions are observed and analyzed to develop an efficient prolonged use of GO plus MnO2 entrapped. The well-known first-order kinetics is assumed to analyze the deactivation of either GO or MnO2 since its stability is affected by a complicated interaction among the operating variables. The first-order deactivation rate constant for GO, kd,E is determined from the progressive decrease in the apparent effectiveness factor for GO, αapp based on the initial GO concentration CE,0 in the gel beads. This is because the decrease in the GO concentration, CE is too difficult to measure but approximately directly proportional to αapp. The kd,E value under any set of operating conditions is determined from the two values of αapp at the start and end of the 24 h reaction. To obtain the kd,E values for the prolonged times, the repeated 24 h reactions are carried out with the same gel beads. Examining the data on kd,E obtained under the various operating conditions gives an empirical correlation of kd,E with the pH value and the P concentration CP which is the time-averaged P concentration during every 24 h reaction. The other variables such as the glucose and gel beads concentrations and the superficial air velocity are found to exert almost no influence on the kd,E value. On the other hand, the deactivation rate constant for MnO2, kd,M is determined from the two values of the intrinsic P decomposition rate constant, kP in the same 24 h reaction as above since the kP value, which is proportional to the MnO2 concentration CM, can be calculated from its apparent value based on the effectiveness factor theory. The kd,M values are empirically correlated with the pH value only. The above two deactivation kinetic models are combined with our previous reaction and mass transfer model for the gel beads in the airlift to simulate the CaG production process in a prolonged batch bioreactor operation. A fair agreement obtained between the observed and calculated time courses of the process suggests the validity of the deactivation models developed. An application of the simulation model also predicts an optimal ratio of the amounts of GO and MnO2 immobilized in the gel beads.