The current approach envisioned to fabricate targets for inertial fusion energy power plants is diffusion of a deuterium-tritium (D-T) gas mixture through the walls of the plastic shell targets at very high pressures (peaking at values up to 128 MPa) and modest temperatures (∼ 400 K). The use of high gas pressure during fabrication is required so that the D-T gas rapidly diffuses into the pellet, which enables the fabrication facility to satisfy the power plant's fueling requirements. D-T gas mixtures at such high pressures raise safety concerns that must be addressed in the design. The combustion of D and T in air is discussed in this paper, as well as high pressure gas hazards and possible means to mitigate these hazards. The US Department of Energy guidance on tritium handling and storage is summarized here. Issues of safety and reliability of various protection systems are also discussed to support designers in tradeoff analyses of confnement types.