Stable operation of a hydrogen isotope separation system is one of the most important issues in the sustainable operation of fusion power plants. Owing to the present limitation in retention time of fusion reaction, fusion reactors are run in repeated batch operations, causing large fluctuating flows in the system. Hence, to reliably produce required products, counteractive operational strategies must be devised. To this end, we perform dynamic optimization in this paper to derive an optimal control policy that can minimize the tritium inventory and satisfy the product quality specifications. In addition, a rigorous dynamic model for packed columns is developed to simulate realistic behaviors of cryogenic distillation. We demonstrate that the optimization results yield vital operational strategies, such as operation mode switching, without any expertise provided.